Dynamic Nonlinear Effects in Asymmetric Catalysis - American

Subscriber access provided by UNIV AUTONOMA DE COAHUILA UADEC

Review

Dynamic Nonlinear Effects in Asymmetric Catalysis Konstantin P. Bryliakov ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b00697 • Publication Date (Web): 03 May 2019 Downloaded from http://pubs.acs.org on May 3, 2019

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Dynamic Nonlinear Effects in Asymmetric Catalysis

Konstantin P. Bryliakov Boreskov Institute of Catalysis, Pr. Lavrentieva 5, Novosibisk 630090. Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russian Federation E-mail: [email protected]

Abstract: For three decades, “conventional” nonlinear effects in asymmetric catalysis, commonly becoming apparent as nonproportional relationship between the enantiomeric purity of the chiral catalyst and that of the chiral reaction product, have been extensively studied from both fundamental and practical perspectives, and thoroughly reviewed. On the contrary, this review is focused on dynamic nonlinear effects, with the catalyst systems exhibiting variation of enantioselectivity over the reaction course, caused by catalyst-product or catalyst-substrate interactions. Namely, such phenomena as asymmetric autoinduction, asymmetric autocatalysis, and asymmetric autoamplification are considered and the corresponding catalytic reactions are surveyed. Whenever available, data on the origins of the observed nonlinearities are presented. Several kinetic schemes, illustrating the nonlinear ee variation over the reaction course, are considered. Possible implications of dynamic nonlinear effects in asymmetric catalysis into the problem of biological homochirality on Earth are discussed briefly.

Keywords: asymmetric catalysis, asymmetric amplification, autoamplification, autocatalysis, autoinduction, dynamic, nonlinear effects

1 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 58

1. Introduction The term “nonlinear effects” was introduced to asymmetric synthesis by Henri Kagan, to identify stereoselective processes featuring nonlinear correlation between the enantiomeric excess of a chiral auxiliary and the optical yield of the product (in either stoichiometric or catalytic mode).1 Kagan distinguished positive and negative nonlinear effects (Figure 1), also regarded as asymmetric amplification and asymmetric depletion,2 on default assuming that the enantiomeric excess of the product (i.e. the overall reaction enantioselectivity) is constant over the reaction course. Various aspects of nonlinear effects (NLEs) of this kind have been studied for decades and have been discussed in detail in many review papers and book chapters.2-11 The common feature of such NLEs is that they are observed in cases when the chiral auxiliary (chiral catalyst for catalytic reactions) is enantiomerically impure, and is capable of forming catalytically active diastereomeric dimers (or higher aggregates).

Figure 1. Concept of positive and negative nonlinear effects (NLE) in a stereoselective reaction as defined by H. Kagan.

Dynamic nonlinear effects (DNLEs) can arise in asymmetric processes whose rate equations are fundamentally nonlinear, i.e. include products of concentrations of reaction substrates and/or reaction products (at least one of those should be chiral and exist as a mixture of enantiomers). In practice, this leads to a variation of the overall reaction enantioselectivity over the reaction course. 2 ACS Paragon Plus Environment

Page 3 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

To date, three kinds of dynamic nonlinear effects in asymmetric catalysis can be distinguished, namely asymmetric autoinduction, asymmetric autocatalysis, and asymmetric autoamplification. The difference between them is illustrated in Figure 2. In the literature, alternative definitions for the above phenomena can be found; for the purposes of this work, entirely focused on catalytic processes, we favor the following formulations. Asymmetric autoinduction in catalysis is the case when the chiral product of the reaction modifies the stereochemical course of the reaction by changing the nature of the catalyst (Figure 2).6,12,13 Asymmetric autoinduction is a phenomenon of high generality, since catalytic reactions with autoinduction can involve the formation of product(s) both different from or identical to, the catalyst. In effect, the scope of asymmetric processes, whose stereochemical course could potentially be affected by asymmetric autoinduction, is, in principle, virtually unlimited. Asymmetric autocatalysis is a special case of asymmetric autoinduction, the catalytic reaction yielding the product identical to the chiral catalyst (Figure 2).6,14,15 Apparently, this phenomenon is much less general; to date, the number of known catalytic reactions, consisting in the self-reproduction of the chiral catalyst, could be counted on one hand. Historically, this special situation was often treated as independent phenomenon, which tradition will be formally kept in this work. In turn, asymmetric autoamplification will be considered as the case when chiral substrate affects the stereochemical course of a catalytic reaction, by changing the nature of the catalyst (Figure 2),16 thereby affecting its own enantiomeric (diastereomeric) purity. By definition, this phenomenon cannot be reduced to, or considered as, a special case of asymmetric autoinduction.

Moreover,

there

is

another

fundamental

peculiarity

of

asymmetric

autoamplification, consisting in that in this case, chiral nature of the reaction product is not compulsory condition (Figure 2). As of today, asymmetric autoamplification has been documented only for oxidative kinetic resolution of secondary alcohols and related substrates.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 58

asymmetric autoinduction:

A

+

B

asymmetric autocatalysis:

A

+

B

P*

P*

(S)-A* asymmetric autoamplification:

[C*-P*]

+

B

P*

[C*-(S)-A*]

P + (S)-A*

(R)-A*

Figure 2. Schematic representation of formal difference between asymmetric autoinduction, asymmetric autocatalysis, and asymmetric autoamplification. A is substrate, B is reactant, C – catalyst, P – product. Asterisks indicate chiral reactants/catalysts/products. Asterisks indicate chiral molecules. It should be mentioned that the existence of asymmetric autocatalysis was theoretically predicted by Frank as far back as in 1953,17 almost four decades before the discovery of the most extensively studied asymmetric autocatalytic reaction – the Soai reaction.18 When discussing the origin of chiral biological life, Frank proposed the formal kinetic scheme (Figure 3), assuming that two enantiomers of the product self-replicate themselves upon interaction with substrate S. Analysis of the corresponding kinetic scheme reveals intrinsically unstable solution, with saddle type equilibrium point, which means that an initial (nonzero) enantiomeric excess could increase up to 100 % ee.19 This scheme may be considered as idealized mathematical model of evolution of small initial enantiomeric imbalance into the present homochiral (D-sugars, L-aminoacids) biological world. Other theoretical models for predicting the evolution of enantiomeric purity in self-replicating systems, taking into account reactant flux in open systems,20,21 different types of non-linearity,22,23,24 as well as fluctuating environment,25,26 were reported. Unlike asymmetric autocatalysis,12,17 asymmetric autoinduction and asymmetric autoamplification were not initially theoretically foreseen and were understood following their experimental observation.


Page 5 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

D

+

S

L

+

S

D

+

L

k1 k1 k2

2D 2L P

Figure 3. Kinetic scheme for symmetrically mutually antagonistic self-reproducing systems, considered by Frank.17 D and L stand for the two enantiomers of the reaction products, S is substrate, P is inactive byproduct.

From the practical synthetic perspective, there is an important potential advantage of asymmetric reactions with nonlinear effects, namely, the enantioselectivity of the corresponding catalytic systems can increase as the reaction proceeds, thus improving the enantiomeric purity of the reaction product. With this idea in mind, as well as with an intention to clarify the molecular mechanisms operating DNLEs, herewith we survey the existing experimental evidences of dynamic nonlinear effects in asymmetric catalytic processes. Peculiarities of phase behavior of non-racemic heterogeneous mixtures are not included (yet mentioned in a few cases). The discussion mainly follows chronological order.

2. Asymmetric autoinduction 2.1. First observation of asymmetric autoinduction In 1989Alberts and Wynberg studied the effect of enantiomerically enriched deuterated (+)-(R)1-phenyl-1-propanol-dl (+24.40) on the addition of ethyllithium to benzaldehyde (Scheme 1, top), and found that the reaction product, PhC*H(OH)Et (1), was enantiomerically enriched ((+)configuration, 17 % ee).27


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(+)-PhC*D(OLi)Et / EtLi PhCHO

PhCHO

PhC*D(OLi)CH2CO2Et LiCH2CO2Et

Page 6 of 58

H3O+ PhC*D(OH)Et + PhC*H(OH)Et

benzene

1

(R*LiO)n

PhC*D(OH)CH2CO2Et + PhC*H(OH)CH2CO2Et 2

THF

Scheme 1. Catalytic addition of ethyllithium to benzaldehyde (top) and catalytic aldol condensation of ethyl acetate with benzaldehyde (bottom).

This was the first reported evidence of influence of reaction product on the stereochemical course of the reaction, the reaction product acting as the chiral ligand for the actual catalyst, (+)-PhC*H(OLi)Et/(+)-PhC*D(OLi)Et. This effect was termed “the principle of asymmetric autoinduction in a C-C bond formation”. Subsequently, the same authors demonstrated the effect of (–)-(S)-ethyl [3-2H]3-phenyl-3-hydroxypropanoate (81 % ee) on the aldol condensation of ethyl acetate with benzaldehyde (Scheme 1, bottom).28 The autoinductive effect was counterproductive, the reaction product 2 having the opposite absolute configuration: (+)-(R)-Ph*CH(OH)CH2CO2Et. Analysis of the overall picture was complicated by partial precipitation of {[LiO-PhCHCH2CO2Et]}n aggregates, enriched in the (+)-(R)-Ph*CH(OH)CH2CO2Et enantiomer of 2.

2.2. Asymmetric autoinduction in catalytic hydrocyanation reactions Danda with co-workers reported the implication of asymmetric autoinduction in the hydrocyanation of 3-phenoxybenzaldehyde, catalyzed by cyclo-[(R)-phenylalanyl-(R)-histidyl] ((R,R)-3)) (Scheme 2, top).29


Page 7 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

O

HN H

CHO O

O

HN

N NC

NH H

H

3

O

+ HCN toluene

O R

4

5a and 5b

OSi(OEt)3

+ HSi(OEt)3

R

Et2O

OH

OH

OHworkup

R

R = Aryl, cycloalky, alkenyl, alkynyl

O

O

O Ti

O

O Ti

H

O

R H

5b

5a

Scheme 2. Catalytic hydrocyanation of 3-phenoxybenzaldehyde (top) and hydrosilylation of ketones with triethoxysilane (bottom).

Evidence was provided for the formation of complex between the (R,R)-3 (presumably poly- or oligomeric30,31) and the (S)-product 4, which was believed to act as the actual catalytically active species.29,30 The authors found that the enantiomeric excess of the reaction product, (S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile, increased with increasing conversion (Figure 4), thus pointing out the dynamic nature of the observed effect. The addition of 8.8 mol. % of (S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (92 % ee) at the beginning of the reaction dramatically improved the enantioselectivity up to > 95 % ee even at moderate conversion levels (Figure 4). Others have disclosed the existence of autoinduction in the hydrocyanation of five different aldehydes in the presence of (R,R)-3, thus establishing autoinduction as a general phenomenon in reactions of this kind.31 The crucial role of incorporation of the cyanohydrine product 4 into the catalyst complex 3 was rationalized in a computational study: such catalyst 7 ACS Paragon Plus Environment

ACS Catalysis

modification apparently enhanced π-interaction in the stereodetermining step and diminished the competing aromatic C-H∙∙∙O=C interaction.32 100 90 80

product ee, %

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 58

70 60 50 40 30 20

30

40

50

60

70

80

90

100

conversion, %

Figure 4. Enantiomeric purity of the cyanohydrin vs. conversion based on the data reported in ref. 29: without added (S)-cyanohydrin (■) and with 8.8 mol. % of added (S)-cyanohydrin having 92 % ee (●).

2.2. Asymmetric autoinduction in catalytic hydrosilylation reaction Nakai with co-workers studied the hydrosilylation of ketones with triethoxysilane in the presence of (R)-1,1ʹ-bi-2-naphthol titanium complex ((R)-BINOL)Ti(OiPr)2 and in the absence of drying agents, such as 4 Å molecular sieves (Scheme 2, bottom). Under the reaction conditions, the enantiomeric excess gradually increased with increasing conversion (from 47 % ee at 20 % conversion up to 55 % ee at 100 % conversion).33 The authors associated this growth with the likely involvement of the “doubly chiral” complex 5b in the asymmetric reaction at later stages, which ensured higher enantioselectivity than the complex 5a, initially generated from the pre-catalyst ((R)-BINOL)Ti(OiPr)2 and HSi(OEt)3, and predominating during the early reaction period.

2.3. Asymmetric autoinduction in the addition of diethylzinc to benzaldehyde The first report on the observation of asymmetric autoinduction in the course of titanium catalyzed addition of diethylzinc to benzaldehyde belongs to Alberts and Wynberg,27 who 8 ACS Paragon Plus Environment

Page 9 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

mentioned such process to be the case in the presence of ((+)-PhC*D(OEt))4Ti, affording chiral (+)-1-phenylpropanol with 32 % ee (Scheme 3, top).27 We notice that no other chiral auxiliaries (only the reaction product) were used for this reaction. A closely related observation was contributed by Walsh with co-workers who reported enantioselectivities up to 84 % ee upon the addition of ZnEt2 to p-methylbenzaldehyde in the presence of catalyst generated in situ from Ti(ORʹ)4 (Rʹ = (S)-1-phenylpropan-1-olate) and achiral bis(sulfonamide) ligands.34 Later, Walsh with co-workers studied the evolution of enantiomeric excess in diethylzinc addition to PhCHO in the presence of titanium complexes with chiral sulfonamide ligands 6-7 (Scheme 3).35,36 The authors documented a dramatic ee evolution with conversion (Figure 5): in the presence of ligand 7a, the enantiomeric purity of (S)-1-phenylpropanol increased from 20 % ee at 10 % conversion up to 79 % ee at 100 % conversion. Even more interestingly, with ligand 7b, (R)-1-phenylpropanol predominantly formed at the beginning of the reaction; however, with the reaction progress, the sense of enantioselectivity reversed (Figure 5). To explain those observations, the authors proposed the following scheme of catalyst evolution with the progress of the reaction (Scheme 3, bottom). It was concluded that the presence of bulkier alkoxides on titanium improved the catalyst enantioselectivity, L*Ti(OR*)2 being significantly more enantioselective than L*Ti(OiPr)2.36 In 1993, Yaozhong with co-workers studied the addition of diethylzinc to benzaldehyde in the presence of additives of the target (R)-1-phenylpropanol, and found moderate enantioselectivity of 14 % ee, which formally corresponds to enantioselective autocatalytic reaction.37 However, in the presence of catalytic amounts of achiral amines (4 mol. %), this reaction demonstrated much higher enantioselectivities up to 49 % ee, thus providing an interesting example of catalytic reaction with asymmetric autoinduction.


ACS Catalysis

PhCHO

H3O+

((+)-PhC*D(OEt))4Ti / ZnEt2

PhC*D(OH)Et + PhC*H(OH)Et

benzene

1

6-7 (8 mol. %) PhCHO + Et2Zn + Ti(OiPr)4 1 eq.

1.2 eq.

1.2 eq.

toluene/hexanes

NHSO2R

Ph

NHSO2R

NHSO2R

Ph

NHSO2R

6 R = Aryl,n-Bu, CF3

Ph Ph

SO2Ar N OiPr Ti OiPr N SO2Ar

Et

OH

Ph

H

7a R = 4-tBu-C6H4 7b R = 2,4-Me2-C6H3 7c R = 4-Me-C6H4

[Ti]-OR*

Ph

[Ti]-OiPr

Ph

SO2Ar N OR* Ti OiPr N SO2Ar

[Ti]-OR*

Ph

[Ti]-OiPr

Ph

SO2Ar N OR* Ti OR* N SO2Ar

reaction progress

Scheme 3. Ti-tetraalkoxide (top) and Ti-sulfonamide catalyzed addition of diethylzinc to benzaldehyde. In the box: simplified mechanism of evolution of catalytically active species (bottom). 80 70 60 50

product ee, %

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 58

40 30 20 10 0 -10 -20 0

10

20

30

40

50

60

70

80

90

100

conversion, %

Figure 5. Plot of ee (%) of 1-phenylpropanol vs. benzaldehyde conversion (%) with ligands 7a (■) and 7b (●).


Page 11 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

2.4. Asymmetric autoinduction in Diels-Alder reaction In 1997, Wulff with co-workers documented asymmetric autoinduction in the Diels-Alder reaction catalyzed by aluminum complexes with axially chiral biphenantrol ligand (Scheme 4).38 The reaction demonstrated 48 % ee at 20 % conversion, the enantiomeric purity increasing up to 82 % ee at 100 % conversion, which was explained by binding the carbonyl cycloolefinic product to the aluminum catalyst. When 0.5 equiv. of enantiopure cycloaddition product was added to the initial reaction mixture, product having 93 % ee (discounted for the initially added enantiopure cycloolefin) was obtained at 40 % conversion level. The authors proposed a method to “switch off” the autoinductive product effect by adding 1 equiv. of proper carbonyl compounds (adamantly aldehyde or pivalaldehyde), which modification improved the enantiomeric excess of the reaction up to 96-98.5 % ee.38

AlEt2Cl (10 mol. %) +

OMe O

(S)-VAPOL (10 mol. %) CH2Cl2 Ph Ph

OMe O

OH OH

(S)-VAPOL

Scheme 4. Al-biphenantrol catalyzed asymmetric Diels-Alder reaction.

2.5. Asymmetric autoinduction in aldol reaction Szlosek and Figadère reported the autoinductive aldol reaction between 2-trimethylsiloxyfuran (2-TMSOF) and a series of achiral aldehydes in the presence of titanium(IV)-BINOL complex (Scheme 5).39 The authors found that the presence of product 8 dramatically affected the optical yield of the addition of 2-TMSOF to octanal. In particular, 5 mol. % of (S,S)-8 improved the optical yield up to >96 % ee, while 5 mol. % of (R,R)-8 deteriorated the ee down to only 40 % ee


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 12 of 58

(cf. 70 % ee without product additives). The chemical yield and the syn:anti ratio of 8 remained constant in all three cases.

R'2RSiO

O

+ R''CHO

Ti(OiPr)4:(R)-BINOL (20 mol. %)

OH O

O

8

R, R' = Me, Ph, tBu R' = alky, aryl, alkenyl

O

O

+

RCHO

Ti(OiPr)4:(R)-BINOL (8 mol. %) THF mol. sieves

OSiMe3 9

R

Et2O

OH

O

R

O O

10

R = Ph, C7H15

Scheme 5. Ti catalyzed asymmetric aldol reactions.

Another example of asymmetric autoinduction in aldol reaction, catalyzed by titanium(IV)-BINOL complex, was contributed by Scettri with co-workers, who studied the condensation of trimethylsilyloxydiene 9 with aldehydes (Scheme 5).40 Intriguingly, it was found that the addition of 5 mol % of either (R)-10 or (S)-10 to the reaction mixture 9 + PhCHO resulted in improved enantioselectivity, 93 and > 99 % ee, respectively, cf. 82 % ee without additives. At the same time, the absolute configuration of the reaction product remained the same, (R)-10, witnessing that the sense of enantioselectivity was controlled by the (R)-BINOL ligand.40 These results were explained by the self-organization of the chiral ligands, i.e. BINOL and the resulting chiral aldol. Trost with co-workers used in situ prepared proline derived zinc complex as catalyst in aldol addition of methyl ynones (Scheme 6).41 High enantioselectivities (up to > 98 % ee) were observed in several cases. From the fundamental perspective, most interesting was the observed reversal of the sense of enantioinduction over the reaction course (Figure 6).41 In the presence of added chiral product, (R)-11, there was no change of the sense of enantioinduction, the latter being consistently higher throughout the course of the reaction than under standard conditions


Page 13 of 58

(Figure 6). The authors concluded that the carbonyl oxygen was important for coordination to zinc in the catalytically active species. Ph Ph

O

R + SiEt3

CHO

EtO

Ph Ph

HO

OH N

OH

N

(10 mol. %) + Et2Zn (10 mol. %)

OEt

THF mol. sieves

OH

O

Me EtO

OEt

SiEt3

11

R = Me, alkenyl, TBSOCH2, CO2Et

Scheme 6. Zn catalyzed aldol addition of methyl ynones.

100 80 60

product ee, %

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

20 0 -20 -40 -60 -80

0

10

20

30

40

50

60

70

80

90

conversion, %

Figure 6. Enantiomeric purity of the addition product vs. conversion based on the data reported in ref. 40: without added (R)-11 (■) and with added (R)-11 (●).

2.6. Asymmetric autoinduction in aminoxylation and amination reactions Blackmond with co-workers reported the proline-catalyzed asymmetric α-aminoxylation of propanal (Scheme 7).42 The authors clearly demonstrated that the product ee increased over the reaction course, while the reaction rate demonstrated nonmonotonous behavior (Figure 7). A similar rate and ee variation was documented for the L-proline catalyzed α-amination of propanal.43 DFT calculations and kinetic studies highlighted the importance of hydrogen bonding 13 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 14 of 58

between L-proline and the chiral product 13; the increasing product concentration was proposed to be the driving force for increasing the concentration of the catalytically active adduct proline∙13, from which the latter is displaced by propanal molecule.44,45 This hypothesis well explained the observed initial rate enhancement, yet leaving the origin of the ee enhancement unaccounted. O +

H

Ph

O

L-proline (5-20 mol. %) N O

CHCl3 or DMSO

H

H

N O

Ph

12

O H

EtO2C +

N N

O

L-proline (20 mol. %) CO2Et

CH2Cl2

H

CO2Et CO2Et N N H 13

Scheme 7. Proline catalyzed α-aminoxylation (top) and α-amination (bottom) of propanal.

Figure 7. Plot of reaction rate and ee (%) of (R)-12 vs. time. Reprinted from ref. 42. Copyright 2004 Wiley.

2.7. Asymmetric autoinduction in other catalytic reactions There have been some other reactions, for which contribution of autoinduction has been invoked. Jørgensen with co-workers observed the autoinductive-type increase of the rate of epoxidation of α,β-unsaturated aldehydes with H2O2 in the presence of a chiral TMS-prolinol organocatalyst, as the reaction proceeded,46 which was explained by the ability of the reaction product to act as a 14 ACS Paragon Plus Environment

Page 15 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

phase-transfer catalyst. Chen and Yang with co-workers reported dramatically different ee vs. time dependences at different temperatures in a [3+3]-annulation of 4-hydroxycoumarin and Morita-Baylis-Hillman acetate, mediated by chiral palladium catalyst (Figure 8).47 The authors hypothesized the kinetically controlled formation of catalytically active combination of PdL* catalyst with (–)-reaction product at low temperature vs. formation of thermodynamically favored combination of PdL* with (+)-product at high temperature, which was proposed to reverse the sense of asymmetric induction.47

Figure 8. Time dependence of enantioselectivity at different temperatures. Reprinted from ref. 47. Copyright 2017 Royal Society of Chemistry.

Carreira with co-workers developed the catalytic synthesis of antiretroviral agent Efavirenz, in which the enantioselectivity of the key step, ZnEt2/nHexLi/(1R,2S)-Npyrrolidinylnorephedrine mediated alkynylation of the ketone precursor, was affected by the reaction product.48 Martínez-Ilarduya and Espinet with co-workers reported a gradual increase of the product enantiomeric purity from 55 % ee to 88 % ee for the addition of Et2Zn to phenyl trifluoromethylketone in the presence of bulky chiral diamines, presumably ascribed to the contribution of asymmetric autoinduction.49 Arguably, the asymmetric synthesis of chiral 1,2aminoalcohols via reduction of the corresponding amino acids with LiAlH4, modified by Nethylaniline, might also be mentioned here (since the product was, formally, the only chirality 15 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 16 of 58

source),50 yet this reaction can be alternatively classified as template-directed asymmetric selfreplication.10,51,52

2.8. Kinetic description of asymmetric autoinduction Let us consider the hydrosilylation of ketones with triethoxysilane.33 This reaction provides a fruitful case for qualitative analysis of the asymmetric autoinduction effect from the kinetic perspective. The kinetic scheme for this reaction can be written as in Figure 9. In addition to the equations for the reaction without autoinduction (Figure 9), one has to take into account the complexation between the product enantiomers and the catalyst, as well as the reactions catalyzed by the product-complexed catalyst. A A

PR PS

A

+ +

+ +

+

cat cat

cat cat

cat·PR

kR kS

+

cat·PR

A

+

cat·PS

A

+

cat·PS

PS

KR

cat·PR

KS

cat·PS

k RR k

A

PR

R

S

k SR k SS

reaction without autoinduction

catalyst-product complexation

PR + cat·PR PS + cat·PR PR + cat·PS

reaction mediated by substrate-complexed catalyst

PS + cat·PS

Figure 9. Simplified kinetic scheme of autoinduction in an asymmetric catalytic process. A is substrate, cat is chiral catalyst, R and S stand for the enantiomers of the chiral product.

The corresponding kinetic equations are the following

d [PR ]  k R [Cat ][A]  k S R [Cat  PS ][A]  k R R [Cat  PR ][A] dt

(1)

d [PS ]  k S [Cat ][A]  k R S [Cat  PR ][A]  k S S [Cat  PS ][A] dt

(2)


Page 17 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

which, taking into account the complexation equilibria (Figure 10) and the mass balance for the catalyst, cat0 = [cat] + [cat·PR] + [cat·PS], gives

d [PR ] k R [A]  K S k S R [A][PS ]  K R k R R [A][PR ] WR   d [PS ] k S [A]  K R k R S [A][PR ]  K S k S S [A][PS ] WS

(3)

where WR and WS are the instantaneous rates of accumulation of the (R)- and (S)-enantiomers of the product, respectively. There are no fundamental limitations on the WR / WS ratio, which could vary within wide range with variation of the concentrations [PR] and [PS]. In practice, however, three most interesting special cases can be considered (for simplicity, let us consider that the system yields preferentially (R)-enantiomer). I. Preferential complexation of (R)-product (KR >> KS). In this case, (3) can be reasonably simplified to (4):

d [PR ] k R [A]  K R k R R [A][PR ]  d [PS ] k S [A]  K R k R S [A][PR ]

(4)

which differential equation has analytical solution [PS ] [P ]  a  a   [P ]   a1 R   2 1  Ln1  a3 R  A0 A0  a3   A0 

(5)

kS KRk RR k RS where a1  R , a 2  , a3  A0 , and A0 is the initial concentration of the substrate kR kR k R

A. This relationship between [PR] and [PS] allows one to calculate and plot ee vs. conversion dependence for this system. In Figure 10A, red trace, such dependence is presented for the parameters values a1  0.05 , a 2  0.5 , a3  30 , demonstrating ee growth similar to those experimentally observed for asymmetric reactions with autoinduction (see above). II. Non-preferential complexation (KR ~ KS), but highly stereoselective homochiral reaction of the complexed catalyst (kRR, kSS >> kSR, kRS). In this case, (3) is simplified to (6):

d [PR ] k R [A]  K R k R R [A][PR ]  d [PS ] k S [A]  K S k S S [A][PS ]

(6)

which has the following solution 17 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 18 of 58

b1b2    [PS ] 1  [PR ]  b3   1  b3  1 A0 b1  A0    

where b1  A0

(7)

k KSk S S K k RR , b2  S , b3  A0 R . Figure 10A, blue trace, demonstrates that kR kS kR

autoinduction-type curve can be readily obtained in this case, too ( b1  1.0 , b2  0.5 , b3  5 ). III. Non-preferential complexation (KR ~ KS) and highly stereoselective heterochiral reaction, mediated by the complexed catalyst (kRR, kSS 99.5 % ee) afforded product with similarly high ee in 10 consequtive reactions (Scheme 10), which formally corresponded to a 7∙107 amplification factor.62 In the same reaction, the spectacular amplification of the extremely low initial enantiomeric imbalance of 0.00005 % ee was converted into (S)-18 with >99.5 % ee 22 ACS Paragon Plus Environment

Page 23 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

within three consecutive runs.63 The possibility of chirality amplification in consecutive reactions was also demonstrated for the diethylzinc addition to 2-ferrocenylethynylpyrimidine-5carboxaldehyde.64 10 times: >99 % yield; >99 % ee

N

OH

N tBu O (20 mol. %, >99.5 % ee)

N N tBu

(iPr)2Zn cumene

N

OH N

tBu

18

Scheme 10. “Practically perfect” asymmetric autocatalytic addition of diisopropylzinc to (2alkynyl-5-pyrimidyl)alkanols.

The origin of the autocatalytic enhancement of chirality remained unclear for a while, until Blackmond and Brown with co-workers explained the observed phenomenon in terms of formation of dimeric homochiral true catalytically active species 19 (Figure 12),65,67 consistent with the modified Kagan’s “ML2 model”.3,4 Kinetic studies witnessed 3rd order kinetics (secondorder in the prochiral aldehyde and first-order in the dimeric homochiral catalyst), pointing to the formation of the transition state incorporating the dimer 19 along with two molecules of the alkanol product.67 On the other hand, the involvement of tetrameric (Zn4) alkoxide aggregate was also hypothesized on the basis of kinetic,68 DFT69-72 and 1H NMR spectroscopic studies.73

O Zn N

N

N

N

Zn O

19

Figure 12. Proposed dimeric structure of the active sites of the Soai reaction.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 24 of 58

The capacity of the Soai reaction to amplify very small (in fact corresponding to statistical fluctuation, Figure 13) enantiomeric imbalance is spectacular: in a separate series of experiments, the authors have demonstrated that even without adding any chiral product, this reaction can afford chiral alkanols with significant enantiomeric excess (15-90 % ee), with quasistochastic preferential formation of either (R)- or (S)-enantiomers.74 Later, spontaneous formation of both enantiomers of the chiral alcohols (in approximately stochastic distribution) in the Soai reaction in the presence of achiral amorphous silica gel75 and achiral amines76 was reported, thus representing a remarkable example of spontaneous absolute asymmetric synthesis.77,78 The latest personal accounts on the Soai reaction and related topics can be found in refs. 79, 80. N R

CHO N + iPr2Zn

Without chiral additives

N R N

N

Enantioenriched (S)-

R N

Statistical ee fluctuation

N R

N

OZniPr

OH

CHO + iPr2Zn N

Enantioenriched (R)-

R

R = CH3 R = tBu C C

N

OH

Stochastic formation of enantioenriched material

Figure 13. Spontaneous highly enantioselective absolute asymmetric synthesis of 5-pyrimidyl alkanol.

3.2. Asymmetric autocatalysis in organocatalytic Mannich reaction In 2007, Tsogoeva with co-workers reported the first example of asymmetric autocatalysis in an organocatalytic Mannich reaction (Scheme 11, top).81 The Mannich product 20 had the same optical configuration as the initially added organoautocatalyst, but its enantiomeric purity was in 24 ACS Paragon Plus Environment

Page 25 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

all cases lower than that of the initial autocatalyst (i.e. there was no amplification of chirality). This could be partially due to in situ racemization of the product.81 The authors proposed a dimeric transition state for this reaction, supported by DFT calculations. Interestingly, conducting the same reaction without the initially added product catalyst (i.e. under nominally achiral starting conditions) yielded chiral products with enantiomeric excesses of up to 9.5% ee,82,83 which might, in principle, be evidence of autocatalytic mechanism with amplification of enantiomeric excess (yet possible role of chiral trace impurities in this process remained unascertained).

OMe

OMe

O OEt H

MeO

(S)-20 or (R)-20

O

(1-50 mol. %, 29-99 % ee)

N

+

O

HN

acetone

H

EtO2C

O

N

* CO2Et

OMe

OMe

syn-21 (10-20 mol. %, 98 % ee)

N

EtO2C

HN

O

buffer

H

OMe

OEt

O

up to 96 % ee

+

N H

O

20

O

H

*

CO2Et

21 (syn + anti) up to 92 % ee (syn)

OMe

OMe

OMe HN

O H

+ EtO2C

N

O

EtO2C

AcOH (50 mol. %) dioxane

H Bef ore reaction: 22 (15 mol. %) 20:1 (syn/ anti) syn: 99% ee anti: 99% ee

HN

O

EtO2C

22 Af ter reaction: 3.2:1 (syn/ anti), 76 % yield syn: 99% ee anti: 99% ee

Scheme 11. Asymmetric autocatalytic Mannich reactions, together with the transition state, proposed by Tsogoeva with co-workers (top, right).

Subsequently, Amedjkouh and Brandberg reported the asymmetric autocatalytic Mannich reaction with cylcohexanone, resulting in the formation of a mixture of the anti and syn products 25 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 26 of 58

in comparable quantities (Scheme 11). The syn product 21 had high enantiomeric purity (up to 92 % ee, the enantiomeric excess of the anti isomer not exceeding 8 % ee).84 Although the chiral amplification was not demonstrated, the reported autocatalytic reaction operated in aqueous media (best of all in pH 7 buffer), which may be considered as a model for the conditions existing on the prebiotic Earch. Later, Wang with co-workers developed the enantioselective autocatalytic Mannich reaction with isovaleraldehyde; with 99 % enantiomerically pure autocatalyst, the reaction yielded 99 % ee reaction product 22, yet having different syn/anti ratio.85

3.3. Asymmetric autocatalytic aldol reaction Basides the autocatalytic Mannich reaction, Mauksch, Tsogoeva and co-workers reported the autocatalytic aldol reaction of acetone and cyclohexanone with p-nitrobenzaldehyde (Scheme 12), which was examined mostly from the spontaneous mirror symmetry breaking perspective.81,82 The authors hypothesized on the mechanism of asymmetric autocatalysis and on the origin of the symmetry breaking,82,86,87 which debate was shared by others.88-91 Apparently, to date, there have been no reports on other reactions demonstrating asymmetric autocatalytic behavior. Some review papers addressing various aspects of this phenomenon may be recommended.13,92-98 O

+

H

NO2

23

O

O

OH

O

OH

(30 mol. %, 95.4 % ee) NO2

acetone 23

NO2

4 % yield, 96 % ee

Scheme 12. Asymmetric aldol reaction of p-nitrobenzaldehyde with cyclohexanone.

3.4. Kinetic description of asymmetric autocatalytic reaction


Page 27 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Although the mechanisms of known asymmetric autocatalytic reactions have not been reliably established, alternative kinetic models for the Mannich and aldol,82,86,87 and Soai64,67,68,99-108 reactions have been proposed and discussed. The common peculiarity of the proposed kinetic models is the consideration of formation of, at least, dimeric (homo- and heterochiral) species, and, possibly, higher oligomers. Another feature is the need for a kind of “cross-inhibition” (playing the role of the 3rd equation in the Frank’s model, see Figure 3), which is essential for accounting for the experimentally observed autocatalytic amplification of ee. The minimal kinetic model for the Soai reaction105 is presented in Figure 14. Although this scheme does not take into account catalytically active dimeric species, which could be expected based on experimental observations,64,65,67,68 this simplified model well predicts the chirality amplification starting from very small initial enantiomeric excess. The simulated picture is presented in Figure 15 (for simulation parameters see ref. 105). Some essential assumptions have been made, i.e. (a) the rate constant k0 should be adequately small, so that the enantioselective process not be overwhelmed by the racemic matter; (b) the heterochiral dimers should be more thermodynamically stable than homochiral dimers,99 and be formed with a higher rate constant, in order to achieve chiral amplification.105 A

+

A

A A

+

+

k0

Z Z

Z + PR

+

Z + PS

PR

+

PS

PR

+

PR

PS

+

PS

PR

k0

uncatalyzed, unspecific product formation

PS

k1

2PR

k1

2PS

k2

autocatalytic reaction

PR·PS

k3 k4

PR·PR

k5 k4

PS·PS

k5


monomer-dimer equilibria (playing the role of cross-inhibition)

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 28 of 58

Figure 14. Minimal kinetic scheme of the Soai reaction. A is substrate, Z is diisopropylzinc, reactant, R and S stand for the enantiomers of zinc alcoxide, PR∙PR and PS∙PS and PR∙PS are the homo- and heterochiral zinc alkoxide dimers.

Quite remarkably, this kinetic model, in combination with computer simulations, also well predicted the observed spontaneous mirror symmetry breaking in the Soia reaction. Upon choosing the rate of mutual inhibition k2 (surpassing the critical value of k2 ≥ 6∙103 M-1 s-1) as the bifurcation parameter, the computer simulations, started under completely achiral conditions, afforded optically active reaction product, with the PR and PS weighed equally over the number of simulations (Figure 16).105 The machine roundoff played the role of fluctuations, eventually affecting the final state of the intrinsically unstable kinetic scheme presented in Figure 14. Obviously, this result is a weighty argument in favor of the concepts of spontaneous emergence of chirality on Earth or elsewhere in the Universe (see Chapter 5).

Figure 15. Numerical simulation of the time evolution of the concentrations of PR and PS starting from initial enantiomeric imbalance of 10-5 % ee. Reprinted from ref. 105. Copyright 2008 Springer.

Other experimental observations, such as the effect of chiral additives, rate of aldehyde consumption, ratio of concentrations of homo- and heterochiral dimers, crystallization conditions, etc., can also be reproduced by simulations, using kinetic schemes that take into consideration various additional processes.101,105,109 28 ACS Paragon Plus Environment

Page 29 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Figure 16. Results of numerical simulations of the final ee in the Soai reaction, with k2 as the bifurcation parameter. Reprinted from ref. 105. Copyright 2008 Springer. In spite of the obvious success of kinetic simulations, qualitatively reproducing various aspects of asymmetric autocatalytic reactions, related experimental kinetic and thermodynamic data, which could be used for refining the kinetic schemes, remain relatively scarce.101,110 However, given the unfading interest to the Soai system, we hope that such data could be obtained in future in-depth mechanistic studies.

4. Asymmetric autoamplification 4.1. Observation of asymmetric autoamplification The third nonlinear effect of our interest is apparently characteristic of kinetic resolution reactions. In 2014 Katsuki with co-workers first hypothesized that substrate can affect the aerobic oxidative kinetic resolution of racemic secondary alcohols in the presence of a chiral ruthenium salen complex:111 the authors discussed this hypothetical effect in terms of substrate inhibition.112 In 2017, it was observed that the oxidative kinetic resolution of 1-arylalkanols with H2O2 in the presence of chiral manganese aminopyridine complex 24 (Scheme 13) demonstrated nonconstant selectivity factor (krel)113 over the reaction course: the krel either monotonously increased, or the initial increase was changed into decline at high conversions (Figure 17A,B).16,114 This variation was most pronounced for the relatively small sec-alcohols (phenyl ethanol, 1-p-tolylethanol), while for bulkier substrates the effect was less evident (Figure 17B). 29 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 30 of 58

OCH2CF3 HO

Y

HO

Y

HO

Y

O

Y

N

24 (0.1 mol. %) +

CH3CN H2O2

X

N

+

X

N

X

major

X

25

Y = H, alkyl, aryl, cycloalkyl

OTf OTf

N

minor

X = alkyl, OMe, Br, aryl

Mn

OCH2CF3 24 N

24

*

HO H2O2

H2O

N N

V Mn

O HO

O N

Ar

Ar

Ar

k Srel HO Ar

N

k rel

+

*

O

N N

V Mn

OH

Ar

+

Ar

Ar

HO

N

Ar

HO

HO

O

HO

O HO

Ar

Ar Ar

N

regular OKR

*

N N

V Mn

k Rrel

O O

N

Ar

OKR with autoamplification

Scheme 13. Oxidative kinetic resolution of 1-arylalkanols and alkyl mandelates in the presence of chiral manganese aminopyridine catalyst (top) and the proposed reaction scheme (bottom).

The origin of the observed variation of krel was disclosed as follows: the chiral catalyst can coordinate both enantiomers of the substrate, giving rise to two diastereoisomeric catalytically active sites, more reactive than the non-coordinated catalyst and having different selectivity toward the enantiomers of the substrate.114 As the reaction proceeds, the share of the less reactive substrate enantiomer increases, entailing the increase of the share of the more selective catalyst∙substrate diastereomer and thus the actual krel. To unambiguously identify this substrate effect on the krel, the term asymmetric autoamplification was proposed.114 Actually, it is not predetermined that the catalyst-substrate complexation should always result in an increase of the selectivity factor; the contrary instance is the kinetic resolution of 1-(2-naphthyl)ethanol, for which the krel was found to decrease monotonously (Figure 17B, red trace), being the so far 30 ACS Paragon Plus Environment

Page 31 of 58

unique example of negative asymmetric autoamplification (autodepletion) in kinetic resolution reactions.16

10

90

8

80

7

70

6

60

5

50

4

40

3

30

2

20

1

10

0

B

100

1-p-tolylethanol

9

0

10

20

30

40

50

60

70

80

0

10

20

30

40

50

60

70

80

ee, %

krel

A

0

9 8 7 6

krel

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

5 4 3 2

90

conversion, %

Figure 17. Plots of ee and the apparent krel vs. conversion for the oxidation of 1-p-tolylethanol in the presence of catalyst 24 (A). Plots of krel vs. conversion for various substrates (B). 1-p-tolyl ethanol (green), 1-phenyl ethanol (black), n-butyl mandelate (green), methyl mandelate (orange), p-t-butylphenyl-1-ethanol (blue), 1-(2-naphthyl)ethanol (red).

Herein, for the oxidative kinetic resolution to take place, the catalyst’s chirality should not be compulsorily predetermined by the chiral, enantiomerically pure ligand. Indeed, small initial enantiomeric excess (of the order 10-20 % ee) was shown to increase several times in the course of oxidation of 1-phenylethanol with H2O2 in the presence of chiral-at-metal complexes 26 and 27 (Scheme 14), bearing conformationally non-rigid achiral aminopyridine ligands, without any other exogenous sources of chirality (Figure 18).115 The substrate itself played the role of the only chiral auxiliary, affecting the equilibrium between two mirror conformers of the 31 ACS Paragon Plus Environment

ACS Catalysis

substrate-complexed catalyst through formation of diastereomeric catalyst∙substrate adducts and thus representing an unconventional case of dynamic control of the catalyst’s chirality by the chiral substrate.115 HO

HO

HO

O

25 or 26 (0.1 mol. %) CN3CN H2O2

+

+

small initial ee

large ee

+

OCH2CF3

_ OTf

OCH3

N

N N N

Mn

OTf

N

OH2

N

Mn

OTf OTf

N

N

OCH3

OCH2CF3

27

26

Scheme 14. Kinetic resolution of scalemic 1-phenylethanol in the presence of achiral Mn complexes. 45 40 35 30 ee, %

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 32 of 58

25

ee0= 13.0%

20 15 10

ee0= 11.4% 0

10 20 30 40 50 60 70 80 90 100

conversion, %

Figure 18. Enantiomeric excess (ee) vs. conversion plots for the kinetic resolution of scalemic 1phenylethanol in the presence of achiral catalyst 26 () and 27 (). Dots represent experimental data; solid lines are theoretical fits according to the kinetic model developed in ref. 115.

4.2.

Kinetic

description

of

the

oxidative

kinetic

autoamplification


resolution

with

asymmetric

Page 33 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

Proposed mechanism of oxidative kinetic resolution with asymmetric autoamplification in the presence of enantiopure catalyst is shown in Scheme 13. The corresponding kinetic scheme, in addition to the unamplified kinetic resolution, has to take into consideration the complexation equilibria between the chiral catalyst and the substrate enantiomers, and the kinetic resolution reactions mediated by the diastereomeric catalyst-substrate complexes (Figure 19). AR

+

cat

AS

+

cat

AR

+

cat

AS

+

AR

+

cat

cat·AR

kR kS

AR

+

+ +

cat·AS

cat·AS

k RR R

S

k SR k

AS

cat·AR

KS

cat·AR cat·AS

P + cat

KR

k AS

P + cat

S

S

reaction without autoamplification

catalyst-substrate complexation

P + cat·AR P + cat·AR P + cat·AS

reaction mediated by substrate-complexed catalyst

P + cat·AS

Figure 19. Model scheme of kinetic resolution with asymmetric autoamplification. P is product, cat is chiral catalyst, AR and AS stand for the enantiomers of the chiral substrate.

This kinetic scheme was discussed previously;16 taking into account the catalyst mass balance cat0 = [cat] + [cat·AR] + [cat·AS], one can obtain

d [A R ] k R [A R ]  K S k S R [A S ][A R ]  K R k R R [A R ][A R ]  d [A S ] k S [A S ]  K R k R S [A R ][AS ]  K S k S S [A S ][AS ]

(10)

Assuming that (R)-substrate is oxidized preferentially (kR > kS, and kXR > kXS, X = R, S), the following, most relevant specific situations may be considered. I. Preferential complexation of (S)-substrate (KS >> KR). Equation (10) is reduced to

d [A R ] k R [A R ]  K S k S R [A S ][A R ]  d [A S ] k S [A S ]  K S k S S [A S ][AS ]

(11)

which in case of initially racemic sec-alcohol, [AR]0 = [AS]0 = C0, has the following solution: 33 ACS Paragon Plus Environment

ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60



[A S ]   C0  1  a3   

a1  1  a3

[A R ]  [A S ]      C0 C  0     where

a1 

kR , kS

a2 

kSR , kSS

Page 34 of 58

a2  a1

,

a3  C 0

(12)

KSk S S . Here, parameters a1 and a2 define the kS

stereoselectivity of the system; in our case, for simplicity, a1, a2 > 1. The third parameter, a3, reflects the contribution of the kinetic resolution mediated by the catalyst-substrate complex vs. the reaction mediated by free catalyst. One can see that the observed krel for this case decreases as the reaction proceeds, irrespective of the value of a3 (Figure 19A, blue curves), thus showing the absence of autoamplification. II. Alternative version of preferential complexation (KR >> KS); equation (10) is reduced to

d [A R ] k R [A R ]  K R k R R [A R ][A R ]  d [A S ] k S [A S ]  K R k R S [A R ][AS ]

(13)

with the following solution:

[A R ]   b1  1  b3  [A S ]  [A R ]   C0    C 0  C0   1  b3      where b1 

b2 b1

,

(14)

K k RR kS k RS , b2  R , b3  C 0 R . Again, parameters b1 and b2 define the kR kR k R

stereoselectivity of the system (in our case, b1, b2 < 1), and b3 reflects the contribution of the kinetic resolution mediated by the catalyst-substrate complex vs. the reaction mediated by free catalyst. Like in case I, the observed krel for this case demonstrates a decrease (yet less abrupt) as the reaction proceeds, irrespective of the value of b3 (Figure 20A, red curves). III. Competitive coordination (KS ~ KR), in combination with slow heterochiral reaction (cat·AS is poorly reactive toward (R)-alcohol, cat·AR is poorly reactive toward (S)-alcohol, kSR kRR), kRS >> kSS).

d [A R ] k R [A R ]  K S k S R [A S ][A R ]  d [A S ] k S [A S ]  K R k R S [A R ][AS ]

(17)

Equation (11) has the following solution:16

1  1   [A ]   [A ]   [A S ]  a1 LambertW  exp 1  d 2 Ln R   d 3 1  R   C0 C 0    d1   d1  C0    where d1 

(18)

kS kR KRk RS d  , , . This solution covers a broad range of d  2 3 C0k S R K S C0 k S R K S KS k S R

different situations that can come to be (Figure 20C) depending on the parameter values: autoamplified-only OKR (non-amplified reaction is negligible; red curve); “standard” OKR with substantial contribution of autoamplification (blue curve); OKR without autoamplification (black curve); and OKR with weak substrate coordination (green curve). 35 ACS Paragon Plus Environment

ACS Catalysis

A

8

a3 = 2.0

7

krel

6

a3 = 0.5

5 4

b3 = 2.0

3

b3 = 0.5

2 0

10

20

30

40

50

60

70

80

90

100

70

80

90

100

70

80

90

100

conversion, %

B

7

c1 = 2.0, c2 = 4.0

6

krel

5

c1 = c2 = 2.0

4 3 2

c1 = 4.0, c2 = 2.0

1 0

10

20

30

40

50

60

conversion, %

C

12 10

krel

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 36 of 58

8 6 4 2 0

10

20

30

40

50

60

conversion, %

Figure 20. The krel vs. conversion plots for case I (A, blue curves, a1 = 3, a2 = 10, variable a3), for case II (A, red curves, b1 = 0.33, b2 = 0.1, variable b3), for case III (B, variable c3 = 0.25, variable c1 and c2 ) and for case IV (C, parameter values can be found in ref. 16).

So, in the presence of preferential (strong) complexation of only one enantiomer of the substrate, asymmetric autoamplification does not occur: with increasing conversion, the 36 ACS Paragon Plus Environment

Page 37 of 58

contribution of the reaction pathway mediated by the substrate-complexed catalyst decreases (in line with decreasing concentration of the substrate), which leads to a decrease of the apparent krel, resulting in asymmetric depletion (Figure 20A). Apparently, for the asymmetric autoamplification to occur, competitive coordination of both enantiomers of the substrate to the catalyst should be the case, in combination with preferred heterochiral reaction, corresponding to case IV considered here. Fitting the experimentally observed krel vs. conversion dependencies for several substrates according to case IV has demonstrated adequacy of this model for the OKR of

ee, %

100 1-phenylethanol 9 90 8 80 7 70 6 60 5 50 4 40 E 3 krel 30 1/ 2  3.6 2 0 20 krel 1 10 0 0 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0

B

krel

10

100 10 1-p-tolylethanol 90 9 80 8 7 70 6 60 5 50 4 40 E krel1 / 2 3 30  4.5 0 2 20 krel 1 10 0 0 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0

conversion

conversion

D

10 9

1-phenylpropanol

8 7

krel

100 10 butyl mandelate 90 9 80 8 7 70 6 60 5 50 4 40 E krel 3 30 1/ 2  3.4 0 2 20 krel 1 10 0 0 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0

ee, %

C

6 5 4 3 2 1

E krel 1/ 2  4.0 0 krel

100 90 80 70 60 50 40 30 20 10

ee, %

krel

A

ee, %

several sec-alcoholic substrates (Figure 21).16

krel

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

0 0,0 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1,0

conversion

conversion

Figure 21. Apparent krel113 (blue) and enantiomeric excess (red) vs. conversion for the oxidation of 1-phenyl ethanol (A), 1-p-tolyl ethanol (B), butyl mandelate (C), 1-phenylpropanol (D) with H2O2 in the presence of catalyst 24. Theoretical fits of krel and ee to experimental data, extrapolated to low and high conversions (green and black, respectively). Reprinted from ref. 16. Copyright 2018 Wiley.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 38 of 58

In the case of OKR with asymmetric autoamplification in the presence of catalysts bearing conformationally nonrigid achiral ligands, the kinetic scheme (cf. Scheme 14) is simplified, since kR = kS, and kRR = kSS, kRS = kSR, yet additionally takes into account the enantiomerization equilibrium between the mirror conformers of the catalyst.115 At the same time, simplified kinetic analysis similar to that described in eq. (17) and (18), vide supra, appeared to be not applicable; in order to correctly reproduce the experimental ee vs. conversion traces (Figure 18), numerical solution of differential equation similar to that in eq. (10) was necessary.115 We notice that this asymmetric autoamplification effect, caused by the interaction of chiral substrate with enantiomerically pure catalyst, should be distinguished from the theoretically predicted krel variation in kinetic resolutions operated by enantioimpure catalysts. In the latter case, as previously formulated, “The nonlinearity … has its origin solely in the intrinsic kinetic rate expressions from the independent reactions of the enantiomeric catalyst species in the reaction mixture.”116 This effect has been described in terms of “effective ee” of the enantioimpure catalyst, which is nonconstant over the reaction course.116

5. Dynamic nonlinear effects and the problem of biological homochirality Asymmetric autocatalysis has been widely invoked when discussing the problem of the origin of biological homochirality on Earth.51,92,117-122 Broadly speaking, such discussion addresses, at least, the issues of (1) origination of (likely small) initial enantiomeric imbalance, followed by (2) its amplification, as well as (3) propagation, (4) self-replication, and (5) evolution of living organisms. Issues (3)-(5) are more the subjects of biochemistry and molecular biology, mature fields in this respect. In turn, issues (1) and (2) seem to be the most challenging for chemists, especially because the conditions existing on prebiotic Earth can never be exactly reproduced for the experimental verification of existing models.


Page 39 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

To answer the question how the initial, prebiotic enantiomeric imbalance could come about, different hypotheses have been put forward, generally falling within two categories: stochastic processes (operated by “chance”, i.e. without chemical or physical directing forces) and determinate processes (directed by external chiral forces).119,123 In the framework of the stochastic model, it is supposed that the production of enantiomerically enriched products can occur accidentally, as a result of fluctuations in the physical and chemical environment of the molecules. Further, for this transient small imbalance not to average out, there should be an amplification mechanism which enhances the enantiomeric excess, ultimately leading to homochiral state.123 The autocatalytic Soai reaction provides a viable model for the scenario described above: first of all, spontaneous mirror symmetry breaking in the Soai reaction has been demonstrated, with quasi-stochastic distribution of the (R)- and (S)-enantiomers,74-78 and secondly, the possibility of reproducible amplification of negligibly small enantiomeric imbalance (down to 5∙10-5 % ee) has been established in this reaction.62,105 It should be noted that the possibility of spontaneous mirror symmetry breaking, with subsequent amplification of enantiomeric excess, was also reported for the autocatalytic Mannich reaction,81,82,86,87 providing further support of the stochastic model. Moreover, the autocatalytic chirality amplification as in the Soai reaction is well compatible with the determinate hypotheses of emergence of the initial enantiomeric imbalance, assuming that the latter emerged owing to an external force or action. Indeed, it was demonstrated that the absolute configuration of the Soai reaction products is dependent on the presence of chiral additives, such as quartz, chiral inorganic crystals, helical silica gel, small chiral (including isotopically chiral) organic molecules, or circularly polarized light (Figure 22),80,97,98,124,125 any of those playing the role of “chiral triggers”.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 40 of 58

Figure22. Model scheme for the origin of chirality and formation of chiral compound with high enantiomeric excess. Reprinted from ref. 80. Copyright 2017 American Chemical Society.

Of course the organometallic Soai reaction proceeds in strictly nonaqueous environment, which is not realistic model of prebiotic media, and therefore cannot be directly taken as the working model of the primordial chirality amplification. Nevertheless, this process illustrates the feasibility of hypothesis of spontaneous driving nonchiral systems toward a single handedness by chemical autocatalysis.120 Moreover, the high sensitivity of the Soai reaction to the presence of chiral additives complements the hypothesis of extraterrestrial origin of the primitive chirality source, suggested by e.g. the reported presence of nonracemic amino acids in Murchison and Murray meteorites.126-128 Although the detailed reaction mechanism remains a matter of debate, the fundamental significance of the Soai reaction, as well as its importance for our understanding of the mechanisms responsible for the origin of natural homochirality, is unquestionable. This prompted the authors of the recent account to stress that “The Soai reaction remains a singular, striking example of amplification of enantiomeric excess in an autocatalytic reaction and a manifestly efficient means of approaching homochirality”.129 Another, non-autocatalytic chemical model of prebiotic amplification of the initial enantiomeric imbalance, is suggested by the oxidative kinetic resolution of scalemic sec-alcohols in the presence of dynamically racemic catalysts (derived from achiral reagents), capable of converting abiotic raw material with small initial enantiomeric imbalance into an enantiomerically pure specimen without action of any exogenous chiral molecules.115 So far this reaction has not exhibited stereoselectivity comparable to that of biological systems, rather being 40 ACS Paragon Plus Environment

Page 41 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

proof of new principle, which has no precedents in the literature. This process operates in a partially aqueous medium, which is a step toward more realistic, from the prebiotic perspective, conditions.

6. Concluding remarks Since the discovery of asymmetric autoinduction by Wynberg in 1989, there has been significant progress in the understanding of this and related dynamic nonlinear effects in asymmetric catalysis. Now, it may be reasonably supposed that reactions influenced by asymmetric autocatalysis, asymmetric autoinduction, and asymmetric autoamplification phenomena, are ubiquitous in asymmetric catalysis.130 At the same time, while processes with asymmetric autoinduction are rather common, there are only a handful of examples of reactions demonstrating asymmetric autocatalytic or asymmetric autoamplification behavior. The latter phenomenon, consisting in the effect of reaction substrate on the stereochemical outcome of the reaction, has been observed only for the oxidative kinetic resolution reactions. To date, purposeful attempts to exploit in practice the major advantage of reactions exhibiting dynamic nonlinear effects in asymmetric catalysis – the possibility of ee enhancement over the reaction course – have been very rare. The major part of research in the field, mostly remaining on the fundamental level, is tightly connected with the problem of emergence of biological homochirality and the origin of life in general. Asymmetric autocatalytic reactions, and the Soai reaction in the first place, provide viable kinetic models for the presumably prebiotic amplification of chirality, that eventually resulted in the present single-handedness of biological molecules on Earth. In addition, the possibility of spontaneous mirror symmetry breaking in asymmetric autocatalytic reactions has been demonstrated, thus supporting the hypothesis of purely stochastic chirality emergence, without need for any external chiral forces or extraterrestrial introduction of the chirality protosource.13,131


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 42 of 58

At present, formal kinetic description of the asymmetric reactions exhibiting dynamic nonlinear effects has been well developed; at the same time, the detailed mechanisms of such reactions have in most cases remained hypothetical. Nevertheless, it is now apparent that the common feature of asymmetric autocatalytic reactions, as well as of kinetic resolutions with asymmetric autoamplification, is that for the nonlinear amplification of chirality to occur, the key catalytic species should incorporate, at least, two chiral molecules of the product (or, in the case of kinetic resolution, of the substrate) at the stereodetermining step. Of course the synthetic, kinetic and mechanistic landscape presented in this review is yet very far from being mature, as well as the state-of-the-art of the problem of emergence of prebiotic homochirality. Nevertheless, it is unquestionable that considering the problem of homochirality through the prism of nonlinear effects in asymmetric catalysis contributes to our understanding of fundamentals of life, a complex and essentially nonlinear phenomenon, in general.

AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]

ORCID Konstantin P. Bryliakov: 0000-0002-7009-8950

Notes The author declares no competing financial interest.

ACKNOWLEDGMENT


Page 43 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

The author thanks the Ministry of Science and Higher Education of Russia (#AAAA-A17117041710080-4). Financial support from the Russian Foundation for Basic Research (#18-3320078) is acknowledged.

References 1.

Puchot, C.; Samuel, O.; Duñach, E.; Zhao, S.; Agami, C.; Kagan, H. B. Nonlinear Effects in Asymmetric Synthesis. Examples in Asymmetric Oxidations and Aldolization reactions. J. Am. Chem. Soc. 1986, 108, 2353-2357.

2.

Kagan, H. B. Nonlinear Effects in Asymmetric Catalysis. In New Frontiers in Asymmetric Catalysis. John Wiley & Sons, Inc.: Hoboken, NJ, 2007.

3.

Guillaneux, D.; Zhao, S. H.; Samuel, O.; Rainford, D.; Kagan, H. B. Nonlinear Effects in Asymmetric Catalysis. J. Am. Chem. Soc. 1994, 116, 9430-9439.

4.

Girard, C.; Kagan, H. B. Nonlinear Effects in Asymmetric Synthesis and Stereoselective Reactions: Ten Years of Investigation. Angew. Chem. Int. Ed. 1998, 37, 2922-2959.

5.

Kagan, H. B. Practical Consequences of Non-Linear Effects in Asymmetric Synthesis. Adv. Synth. Catal. 2001, 343, 227-233.

6.

Fenwick, D. R.; Kagan, H. B. Asymmetric Amplification. In Topics in Stereochemistry, vol. 22. John Wiley & Sons, Inc.: Weinheim, DE, 1999.

7.

Johnson, Jr., D. W.; Singleton, D. A. Nonlinear Effects in Kinetic Resolutions. J. Am. Chem. Soc. 1999, 121, 9307-9312.

8.

Blackmond, D. G. Kinetic Aspects of Nonlinear Effects in Asymmetric Catalysis. Acc. Chem. Res. 2000, 33, 402-411.

9.

Faller, J. W.; Lavoie, A. R.; Parr, J. Chiral Poisoning and Asymmetric Activation. Chem. Rev. 2003, 103, 3345-3368.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

10.

Page 44 of 58

Satyanarayana, T.; Abraham, S.; Kagan, H. B. Nonlinear Effects in Asymmetric Catalysis. Angew. Chem. Int. Ed. 2009, 48, 456-494.

11.

Walsh, P. J.; Kozlowski, M. C. Fundamentals of Asymmetric Catalysis. University Science Books: Sausalito, CA, 2009

12.

Wynberg, H. Asymmetric Autocatalysis: Facts and Fancy. J. Macromol. Sci. Chem. Part A 1989, 26, 1033-1041.

13.

Todd, M. H. Asymmetric Autocatalysis: Product Recruitment for the Increase in the Chiral Environment (PRICE). Chem. Soc. Rev. 2002, 31, 211-222.

14.

Such situation is also occasionally termed catalytic asymmetric automultiplication (ref. 15).

15.

Shibata, T.; Morioka, H.; Hayase, T.; Choji, K.; Soai, K. Highly Enantioselective Catalytic Asymmetric Automultiplication of Chiral Pyrimidyl Alcohol. J. Am. Chem. Soc. 1996, 118, 471-472.

16.

Talsi, E. P.; Bryliakov, K. P. Autoamplification-Enhanced Oxidative Kinetic Resolution of sec-Alcohols and Alkyl Mandelates, and its Kinetic Model. ChemCatChem 2018, 10, 2693-2699.

17.

Frank, F. C. On Spontaneous Asymmetric Synthesis. Biochim. Biophys. Acta 1953, 11, 459-463.

18.

Soai, K.; Niwa, S.; Hori, H. Asymmetric Self-catalytic Reaction. Self-production of Chiral 1-(3-Pyridyl)alkanols as Chiral Self-catalysts in the Enantioselective Addition of Dialkylzinc Reagents to Pyridine-3-carbaldehyde. J. Chem. Soc. Chem. Commun. 1990, 982-983.

19.

de Min, M.; Levy, G.; Micheau, J. C. Chiral Resolutions, Asymmetric Synthesis and Amplification of Enantiomeric Excess. J. Chim. Phys. Phys.-Chim. Biol. 1988, 85, 603619.


Page 45 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

20.

Seelig, F. F. Systems-theoretic Model for the Spontaneous Formation of Optical Antipodes in Strongly Asymmetric Yield. J. Theor. Biol. 1971, 31, 355-361.

21.

Seelig, F. F.; Rossler, O. E. Model of a Chemical Reaction Flip-flop with one Unique Switching Input. Naturforsch. 1972, 27b, 1441-1444.

22.

Decker, P. Spatial, Chiral, and Temporal Self-organization through Bifurcation in “Bioids,” Open Systems Capable of a Generalized Darwinian Evolution. Ann. N.Y. Acad. Sci. 1979, 316, 236-250.

23.

Decker, P. Origins of Optical Activity in Nature, D. C. Walker, Ed., Elsevier: Amsterdam, NL, 1979.

24.

Iwamoto, K.; Seno, M. On a Model Chemical System Related to Absolutely Asymmetric Synthesis. J. Chem. Phys. 1982, 76, 2347-2351.

25.

Kondepundi, D. K.; Nelson, G. W. Weak Neutral Currents and the Origin of Biomolecular Chirality. Nature 1985, 314, 438-441.

26.

Avetisov, V. A.; Gol’danskii, V. I. Physical Aspects of Mirror Symmetry Breaking of the Bioorganic World. Phys. Usp. 1996, 39, 819-835.

27.

Alberts, A. H.; Wynberg, J. Am. Chem. Soc. 1989, 111, 7265-7266.

28.

Alberts, A. H.; Wynberg, H. The Role of the Product in Asymmetric C-C Bond Formation: Stoichiometric and Catalytic Enantioselective Autoinduction. J. Chem. Soc. Chem. Commun. 1990, 453-454

29.

Danda, H.; Nishikawa, H.; Otaka, K. Enantioselective Autoinduction in the Asymmetric Hydrocyanation of 3-Phenoxybenzaldehyde Catalyzed by Cyclo[ (R)phenylalanyl-(R)-histidyl]. J. Org. Chem. 1991, 56, 6740-6741.

30.

Shvo, Y.; Gal, M.; Becker, Y.; Elgavi, A. Asymmetric I-Iydrocyanation of Aldehydes with Cyclo-dipeptides: A New Mechanistic Approach. Tetrahedron: Asymmetry 1996, 7, 911-924.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

31.

Page 46 of 58

Kogut, E. F.; Thoen, J. C.; Lipton, M. A. Examination and Enhancement of Enantioselective Autoinduction in Cyanohydrin Formation by Cyclo[(R)-His-(R)-Phe]. J. Org. Chem. 1998, 63, 4604-4610.

32.

Schoenebeck, F.; Houk, K. N. Theoretical Study of the Catalysis of Cyanohydrin Formation by the Cyclic Dipeptide Catalyst cyclo[(S)-His-(S)-Phe]. J. Org. Chem. 2009, 74, 1464-1472.

33.

Imma, H.; Mori, M.; Nakai, T. Asymmetric Catalytic Hydrosilylation of Ketones with Triethoxysilane Using a Chiral Binaphthol-Titanium Complex. SYNLETT 1996, 12291230.

34.

Balsells, J.; Walsh, P. J. The Use of Achiral Ligands to Convey Asymmetry: Chiral Environment Amplification. J. Am. Chem. Soc. 2000, 122, 1802-1803.

35.

Balsells, J.; Costa, A. M.; Walsh, P. J. Temperature-Dependent Nonlinear Effects and Catalyst Evolution in the Asymmetric Addition of Diethylzinc to Benzaldehyde. Isr. J. Chem. 2001, 41, 251-261.

36.

Costa, A. M.; Carrol, P. J.; Walsh, P. J. Dramatic Catalyst Evolution in the Asymmetric Addition of Diethylzinc to Benzaldehyde. Tetrahedron 2005, 61, 6442-6446.

37.

ShengJian, L.; Yaozhong, J.; Aiqiao, M.; Guishu, Y. Asymmetric Synthesis. Part 19. Asymmetric Autocatalysis of (R)-I-Phenylpropan-1-ol Mediated by a Catalytic Amount of Amine in the Addition of Diethylzinc to Benzaldehyde. J. Chem. Soc. Perkin Trans. 1, 1993, 885-886.

38.

Heller, D. P.; Goldberg, D. R.; Wulff, W. D. Positive Cooperativity of Product Mimics in the Asymmetric Autoinduction of Diels-Alder Reactions Catalyzed by a VAPOLAluminum Catalyst. J. Am. Chem. Soc. 1997, 119, 10551-10552.

39.

Szlosek,

M.;

Figadère,

B.

Highly

Enantioselective

Aldol

Reaction

with

2 ‐ Trimethylsilyloxyfuran: The First Catalytic Asymmetric Autoinductive Aldol Reaction. Angew. Chem. Int. Ed. 2000, 39, 1799-1801. 46 ACS Paragon Plus Environment

Page 47 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

40.

De Rosa, M.; Acosella, M. R.; Soriente, A.; Scettri, A. Asymmetric Auto-inductive Aldol Reaction by Self-assembly of Chiral Ligands. Tetrahedron: Asymmetry 2001, 12, 1529-1531.

41.

Trost, B. M.;. Fettes, A.; Shireman, B. T. Direct Catalytic Asymmetric Aldol Additions of Methyl Ynones. Spontaneous Reversal in the Sense of Enantioinduction. J. Am. Chem. Soc. 2004, 126, 2660-2661.

42.

Mathew, S. P.; Iwamura, H.; Blackmond, D. G. Amplification of Enantiomeric Excess in a Proline-Mediated Reaction. Angew. Chem. Int. Ed. 2004, 43, 3317-3321.

43.

Iwamura, H.; Mathew, S. P.; Blackmond, D. G. In Situ Catalyst Improvement in the Proline-Mediated -Amination of Aldehydes. J. Am. Chem. Soc. 2004, 126, 1177011771.

44.

Iwamura, H.; Wells, Jr., D. H.; Mathew, S. P.; Klussmann, M.; Armstrong, A.; Blackmond, D. G. Probing the Active Catalyst in Product-Accelerated ProlineMediated Reactions. J. Am. Chem. Soc. 2004, 126, 16312-16313.

45.

Mathew, S. P.; Klussmann, M.; Iwamura, H.; Wells, Jr., D. H.; Armstrong, A.; Blackmond, D. G. A Mechanistic Rationalization of Unusual Kinetic Behavior in Proline-mediated C–O and C–N Bond-forming Reactions. Chem. Commun. 2006, 4291-4293.

46.

Davis, R. L.; Jensen, K. L.; Gschwend, B.; Jørgensen, K. A. On the Mechanism of the Organocatalytic Asymmetric Epoxidation of ,-Unsaturated Aldehydes. Chem. Eur. J. 2014, 20, 64-67.

47.

Wang, S.; Xiao, J.; Li, J.; Xiang, H.; Wang, C.; Chen, X.; Carter, R. G.; Yang, H. Discovery of Temperature-dependent, Autoinductive Reversal of Enantioselectivity: Palladium-mediated [3+3]-Annulation of 4-Hydroxycoumarins. Chem. Commun. 2017, 53, 4441-4444.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

48.

Page 48 of 58

Chinkov, N.; Warm, A.; Carreira, E. M. Asymmetric Autocatalysis Enables an Improved Synthesis of Efavirenz. Angew. Chem. Int. Ed. 2011, 50, 2957-2961.

49.

Calvillo-Barahona, M.; Casares, J. A.; Cordovilla, C.; Genov, M. N.; MartínezIlarduya, H. M.; Espinet, P. Diamine-Catalyzed Addition of ZnEt2 to PhC(O)CF3: Two Mechanisms and Autocatalytic Asymmetric Enhancement. Chem. Eur. J. 2014, 20, 14800-14806.

50.

Shibata, T.; Takahashi, T.; Konishi, T.; Soai, K. Asymmetric Self-Replication of Chiral 1,2-Amino Alcohols by Highly Enantioselective Autoinductive Reduction. Angew. Chem. Int. Ed. Engl. 1997, 36, 2458-2460.

51.

Muñiz, K. On the Stereochemical Course of Self-Replication in Secondary Cycle Sharpless Aminohydroxylation. Adv. Synth. Catal. 2005, 347, 275-281.

52.

Bissette, A. J.; Fletcher, S. P. Mechanisms of Autocatalysis. Angew. Chem. Int. Ed. 2013, 52, 12800-12826.

53.

Soai, K.; Hayase, T.; Shimada, C.; Isobe, K. Catalytic Asymmetric Synthesis of Chiral Diol, Bis[2-(l-hydroxyalkyl)-phenyl]ether, an Asymmetric Autocatalytic Reaction. Tetrahedron: Asymmetry 1994, 5, 789-792.

54.

Soai, K.; Hayase, T.; Takai, K. Catalytic Chirally Self-replicating Molecule. Asymmetric Autocatalytic Reaction of a Zinc Alkoxide of Chiral 1-Ferrocenyl-2methylpropan-1-ol. Tetrahedron: Asymmetry 1995, 6, 637-638.

55.

Shibata, T.; Morioka, H.; Tanji, S.; Hayase, T.; Kodaka, Y.; Soai, K. Enantioselective Synthesis of Chiral 5-Carbamoyl-3-pyridyl Alcohols by Asymmetric Autocatalytic Reaction. Tetrahedron Lett. 1996, 37, 8783-8786.

56.

Shibata, T.; Choji, K.; Morioka, H.; Hayase, T.; Soai, K. Highly Enantioselective Synthesis of a Chiral 3-Quinolylalkanol by an Asymmetric Autocatalytic Reaction. Chem. Commun. 1996, 751-


Page 49 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

57.

Shibata, T.; Morioka, H.; Hayase, T.; Choji, K.; Soai, K. Highly Enantioselective Catalytic Asymmetric Automultiplication of Chiral Pyrimidyl Alcohol. J. Am. Chem. Soc. 1996, 118, 471-472.

58.

Soai, K.; Shibata, Y.; Morioka, H.; Choji, K. Asymmetric Autocatalysis and Amplification of Enantiomeric Excess of a Chiral Molecule. Nature 1995, 378, 767768.

59.

Bolm, C.; Bienewald, F.; Seger, A. Asymmetric Autocatalysis with Amplification of Chirality. Angew. Chem. Int. Ed. 1996, 35, 1657-1659.

60.

Shibata, T.; Choji, K.; Hayase, T.; Aizu, Y.; Soai, K. Asymmetric Autocatalytic Reaction of 3-Quinolylalkanol with Amplification of Enantiomeric Excess. Chem. Commun. 1996, 1235-1236.

61.

Shibata, T.; Hayase, T.; Yamamoto, J.; Soai, K. One-pot Asymmetric Autocatalytic Reaction with Remarkable Amplification of Enantiomeric Excess. Tetrahedron: Asymmetry 1997, 8, 1717-1719.

62.

Shibata, T.; Yonekubo, S.; Soai, K. Practically Perfect Asymmetric Autocatalysis with (2-Alkynyl-5-pyrimidyl)alkanols. Angew. Chem. Int. Ed. 1999, 38, 659-661.

63.

Sato, I.; Urabe, H.; Ishiguro, S.; Shibata, T.; Soai, K. Amplification of Chirality from Extremely Low to Greater than 99.5% ee by Asymmetric Autocatalysisls. Angew. Chem. Int. Ed. 2003, 42, 315-317.

64.

Lutz, F.; Kawasaki, T.; Soai, K. Asymmetric Autocatalysis of a Ferrocene-containing Chiral Compound with Amplification of Chirality. Tetrahedron: Asymmetry 2006, 17, 486-490.

65.

Blackmond, D. G.; McMillan, C. R.; Ramdeehul, S.; Schorm, A.; Brown, J. M. Origins of Asymmetric Amplification in Autocatalytic Alkylzinc Additions. J. Am. Chem. Soc. 2001, 123, 10103-10104.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

66.

Page 50 of 58

Blackmond, D. G. Kinetic Aspects of Non-linear Effects in Asymmetric Synthesis, Catalysis, and Autocatalysis. Tetrahedron: Asymmetry 2010, 21, 1630-1634.

67.

Blackmond, D. G. Mechanistic Study of the Soai Autocatalytic Reaction Informed by Kinetic Analysis. Tetrahedron: Asymmetry 2006, 17, 584-589.

68.

Buono, F. G.; Blackmond, D. G. Kinetic Evidence for a Tetrameric Transition State in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes. J. Am. Chem. Soc. 2003, 125, 8978-8979.

69.

Gridnev, I. D.; Brown, J. M. Asymmetric autocatalysis: Novel structures, novel mechanism? Proc. Natl. Acad. Sci. 2004, 101, 5727-5731.

70.

Klankermayer, J.; Gridnev, I. D.; Brown, J. M. Role of the Isopropyl Group in Asymmetric Autocatalytic Zinc Alkylations. Chem. Commun. 2007, 3151-3153.

71.

Schiaffino, L.; Ercolani, G. Unraveling the Mechanism of the Soai Asymmetric Autocatalytic Reaction by First ‐Principles Calculations: Induction and Amplification of Chirality by Self ‐Assembly of Hexamolecular Complexes. Angew. Chem. Int. Ed. 2008, 47, 6832-6835.

72.

Ercolani, G.; Schiaffino, L. Putting the Mechanism of the Soai Reaction to the Test: DFT Study of the Role of Aldehyde and Dialkylzinc Structure. J. Org. Chem. 2011, 76, 2619-2626.

73.

Gehring, T.; Quaranta, M.; Odell, B.; Blackmond, D. G.; Brown, K. M. Observation of a Transient Intermediate in Soai’s Asymmetric Autocatalysis: Insights from 1H NMR Turnover in Real Time. Angew. Chem. Int. Ed. 2012, 51, 9539-9542.

74.

Soai, K.; Sato, I.; Shibata, T.; Komiya, S.; Hayashi, M.; Matsueda, Y.; Imamura, H.; Hayase, T.; Morioka, H.; Tabira, H.; Yamamoto, J.; Kowata, Y. Asymmetric Synthesis of Pyrimidyl Alkanol without Adding Chiral Substances by the Addition of Diisopropylzinc to Pyrimidine-5-carbaldehyde in Conjunction with Asymmetric Autocatalysis. Tetrahedron: Asymmetry 2003, 14, 185-188. 50 ACS Paragon Plus Environment

Page 51 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

75.

Kawasaki, T.; Suzuki, K.; Shimizu, M.; Ishikawa, K.; Soai, K. Spontaneous Absolute Asymmetric Synthesis in the Presence of Achiral Silica Gel in Conjunction with Asymmetric Autocatalysis. Chirality 2006, 18, 479-482.

76.

Suzuki, K.; Hatase, K.; Nishiyama, D.; Kawasaki, T.; Soai, K. Spontaneous Absolute Asymmetric Synthesis Promoted by Achiral Amines in Conjunction with Asymmetric Autocatalysis. J. Syst. Chem. 2010, 1, 5. DOI: 10.1186/1759-2208-1-5

77.

Singleton, D. A.; Vo, L. K. A Few Molecules Can Control the Enantiomeric Outcome. Evidence Supporting Absolute Asymmetric Synthesis Using the Soai Asymmetric Autocatalysis. Org. Lett. 2003, 5, 4337-4339.

78.

Lente, G. Stochastic Interpretation of the Asymmetry of Enantiomeric Distribution Observed in the Absolute Asymmetric Soai Reaction. Tetrahedron: Asymmetry 2010, 22, 1595-1599.

79.

Soai, K.; Kawasaki, T.; Matsumoto, A. Asymmetric Autocatalysis of Pyrimidyl Alkanol and Related Compounds. Self-replication, Amplification of Chirality and Implication for the Origin of Biological Enantioenriched Chirality. Tetrahedron 2018, 74, 1973-1990.

80.

Soai, K.; Matsumoto, A. Asymmetric Autocatalysis and the Origin of Homochirality. In Stereochemistry and Global Connectivity: The Legacy of Ernest L. Eliel, vol. 2. H. N. Cheng, C. A. Maryanoff, B. D. Miller, D. Grob Schmidt, Eds., American Chemical Society: Washington, DC, 2017.

81.

Mauksch, M.; Tsogoeva, S. B.; Martynova, I. M.; Wei, S. Evidence of Asymmetric Autocatalysis in Organocatalytic Reactions. Angew. Chem. Int. Ed. 2007, 46, 393-396.

82.

Mauksch, M.; Tsogoeva, S. B.; Wei, S.; Martynova, I. M. Demonstration of Spontaneous Chiral Symmetry Breaking in Asymmetric Mannich and Aldol Reactions. Chirality 2007, 19, 816-825.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

83.

Page 52 of 58

Held, F. E.; Fingerhut, A.; Tsogoeva, S. B. Insights into the Spontaneous Emergence of Enantioselectivity in an Asymmetric Mannich Reaction Carried out without External Catalyst. Tetrahedron: Asymmetry 2012, 23, 1663-1669.

84.

Amedjkouh, M.; Brandberg, M. Asymmetric Autocatalytic Mannich Reaction in the Presence of Water and its Implication in Prebiotic Chemistry. Chem. Commun. 2008, 3043-3045.

85.

Wang, X.; Zhang, Y.; Tan, H.; Wang, Y.; Han, P.; Wang, D. Z. Enantioselective Organocatalytic Mannich Reactions with Autocatalysts and Their Mimics. J. Org. Chem. 2010, 75, 2403-2406.

86.

Mauksch, M.; Tsogoeva, S. B. Spontaneous Emergence of Homochirality via Coherently Coupled Antagonistic and Reversible Reaction Cycles. ChemPhysChem 2008, 9, 2359-2371.

87.

Mauksch, M.; Wei, S.; Freund, M.; Zamfir, A.; Tsogoeva, S. B. Spontaneous Mirror Symmetry Breaking in the Aldol Reaction and its Potential Relevance in Prebiotic Chemistry. Origins Life Evol. Biosphere 2010, 40, 79-91.

88.

Blackmond, D. G. "If Pigs Could Fly" Chemistry: a Tutorial on the Principle of Microscopic Reversibility. Angew. Chem. Int. Ed. 2009, 48, 2648-2654.

89.

Blackmond, D. G. Challenging the Concept of "Recycling" as a Mechanism for the Evolution of Homochirality in Chemical Reactions. Chirality 2009, 21, 359-362.

90.

Valero, G.; Ribó, J. M.; Moyano, A. Absolute Asymmetric Synthesis in Enantioselective Autocatalytic Reaction Networks: Theoretical Games, Speculations on Chemical Evolution and Perhaps a Synthetic Option. Chem. Eur. J. 2014, 20, 1739517408.

91.

Romero-Fernández, M. P.; Babiano, R.; Cintas, P. On the Asymmetric Autocatalysis of Aldol Reactions: The Case of 4-Nitrobenzaldehyde and Acetone. A Critical Appraisal with a Focus on Theory. Chirality 2018, 30, 445-456. 52 ACS Paragon Plus Environment

Page 53 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

92.

Soai, K.; Shibata, T.; Sato, I. Enantioselective Automultiplication of Chiral Molecules by Asymmetric Autocatalysis. Acc. Chem. Res. 2000, 33, 382-390.

93.

Soai, K.; Shibata, T.; Sato, I. Discovery and Development of Asymmetric Autocatalysis. Bull. Chem. Soc. Jpn. 2004, 77, 1063-1073.

94.

Soai, K.; Kawasaki, T.; Sato, I. Asymmetric Autocatalysis with Amplification of Chirality and Origin of Chiral Homogeneity of Biomolecules. In New Frontiers in Asymmetric Catalysis. John Wiley & Sons, Inc.: Hoboken, NJ, 2007.

95.

Soai, K.; Kawasaki, T. Asymmetric Autocatalysis with Amplification of Chirality. Top. Curr. Chem. 2008, 284, 1-33.

96.

Soai, K.; Kawasaki, T. Asymmetric Autocatalysis with Amplification of Chirality. In Amplification of Chirality. Springer: Berlin, DE, 2008.

97.

Soai, K.; Kawasaki, T.; Matsumoto, A. The Origins of Homochirality Examined by Using Asymmetric Autocatalysis. Chem. Rec. 2014, 14, 70-83.

98.

Soai, K.; Kawasaki, T.; Matsumoto, A. Asymmetric Autocatalysis of Pyrimidyl Alkanol and Its Application to the Study on the Origin of Homochirality. Acc. Chem. Res. 2014, 47, 3643-3654.

99.

Islas, J. R.; Lavabre, D.; Grevy, J. M.; Lamoneda, R. H.; Cabrera, H. R.; Micheau, J. C.; Buhse, T. Mirror-symmetry Breaking in the Soai Reaction: A Kinetic Understanding. Proc. Natl. Acad. Sci. 2005, 102, 13743-13748.

100. Sato, I.; Omiya, D.; Tsukiyama, K.; Ogi, Y.; Soai, K. Tetrahedron: Asymmetry 2001, 12, 1965-1969. 101. Sato, I.; Omiya, D.; Igarashi, H.; Kato, K.; Ogi, Y.; Tsukiyama, K.; Soai, K. Relationship Between the Time, Yield, and Enantiomeric Excess of Asymmetric Autocatalysis of Chiral 2-Alkynyl-5-pyrimidyl Alkanol with Amplification of Enantiomeric Excess. Tetrahedron: Asymmetry 2003, 14, 975-979.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 54 of 58

102. Buhse, T. A Tentative Kinetic Model for Chiral Amplification in Autocatalytic Alkylzinc Additions. Tetrahedron: Asymmetry 2003, 14, 1055-1061. 103. Schiaffino, L.; Ercolani, G. Amplification of Chirality and Enantioselectivity in the Asymmetric Autocatalytic Soai Reaction. ChemPhysChem 2009, 10, 2508-2515. 104. Brown, J. M.; Gridnev, I.; Klankermayer, J. Asymmetric Autocatalysis with Organozinc Complexes; Elucidation of the Reaction Pathway. Top. Curr. Chem. 2008, 284, 35-65. 105. Lavabre, D.; Micheau, J. C.; Islas, J. R.; Buhse, T. Kinetic Insight into Specific Features of the Autocatalytic Soai Reaction. Top. Curr. Chem. 2008, 284, 67-96. 106. Micheau, J. C.; Coudret, C.; Cruz, L. M.; Buhse, T. Amplification of Enantiomeric Excess, Mirror-image Symmetry Breaking and Kinetic Proofreading in Soai Reaction Models with Different Oligomeric Orders. Phys. Chem. Chem. Phys. 2012, 14, 1323913248. 107. Gridnev, I. D.; Vorobiev, A. Kh. Quantification of Sophisticated Equilibria in the Reaction Pool and Amplifying Catalytic Cycle of the Soai Reaction. ACS Catal. 2012, 2, 2137-2149. 108. Stich, M.; Ribó, J. M.; Blackmond, D. G.; Hochberg, D. Necessary Conditions for the Emergence of Homochirality via Autocatalytic Self-replication. J. Chem. Phys. 2016, 145, 074111109. Noble-Terán, M.; Cruz, J. M.; Micheau, J. C.; Buhse, T. A Quantification of the Soai Reaction. ChemCatChem 2018, 10, 642-648. 110. Quaranta, M.; Gehring, T.; Odell, B.; Brown, K. M.; Blackmond, D. G. Unusual Inverse Temperature Dependence on Reaction Rate in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes. J. Am. Chem. Soc. 2010, 132, 15104-15107.


Page 55 of 58 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

111. Mizoguchi, H.; Uchida, T.; Katsuki, T. Ruthenium-catalyzed oxidative kinetic resolution of unactivated and activated secondary alcohols with air as the hydrogen acceptor at room temperature. Angew. Chem. Int. Ed. 2014, 53, 3178-3182. 112. We must notice, however, that in Katsuki’s ruthenium based system, the actual (observed) selectivity factor, krel, determining the ratio of the oxidation rates of the more and the less reactive enantiomers, was constant during the reaction (Figure S2 of the Supporting Information for ref. 111). 113. krel was calculated as ln[(1-c)(1-ee)]/ln[(1-c)(1+ee)], where c is conversion, ee is enantiomeric esxess: Kagan, H. B.; Fiaud, J. C. Kinetic Resolution, In Topics in Stereochemistry, vol. 18. E. L. Eliel, J. C. Fiaud, Eds., John Wiley & Sons, Inc.: New York, NY, 1988. 114. Talsi, E. P.; Samsonenko, D. G.; Bryliakov, K. P. Asymmetric Autoamplification in the Oxidative Kinetic Resolution of Secondary Benzylic Alcohols Catalyzed by Manganese Complexes. ChemCatChem 2017, 9, 2599-2607. 115. Talsi, E. P.; Bryliakova A. A.; Ottenbacher, R. V.; Rybalova, T. V.; Bryliakov, K. P. Kinetic Resolution Meets Dynamic Chirality Control to Exemplify Non-Autocatalytic Chemical Model of Prebiotic Chirality Amplification. Submitted. 116. Blackmond, D. G. Kinetic Resolution Using Enantioimpure Catalysts: Mechanistic Considerations of Complex Rate Laws. J. Am. Chem. Soc. 2001, 123, 545-553. 117. Feringa, B. L.; Van Delden, R. A. Absolute Asymmetric Synthesis: The Origin, Control, and Amplification of Chirality. Angew. Chem. Int. Ed. 1999, 38, 3418-3438. 118. Mikami, K.; Yamanaka, M. Symmetry Breaking in Asymmetric Catalysis: Racemic Catalysis to Autocatalysis. Chem. Rev. 2003, 103, 3369-3400. 119. Klabunovskii, E. I. Homochirality and Its Significance for Biosphere and the Origin of Life Theory. Russ. J. Org. Chem. 2012, 48, 881-901.


ACS Catalysis 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 56 of 58

120. Ruiz-Mirazo, K.; Briones, C.; de la Escosura, A. Prebiotic Systems Chemistry: New Perspectives for the Origins of Life. Chem. Rev. 2014, 114, 285-366. 121. Weissbuch, I.; Lahav, M. Crystalline Architectures as Templates of Relevance to the Origins of Homochirality. Chem. Rev. 2011, 111, 3236-3237. 122. Blackmond, D. G. Asymmetric Autocatalysis and its Implications for the Origin of Homochirality. Proc. Natl. Acad. Sci. 2004, 101, 5732-5736. 123. Blackmond, D. G. The Origin of Biological Homochirality. Cold Spring Harbor Perspect. Biol. 2010, 2, a002147. 124. Soai, K.; Sato, I.; Shibata. T. Asymmetric Autocatalysis and the Origin of Homochirality of Biomolecules. In Methodologies in Asymmetric Catalysis, S. Malhotra, ACS Symposium Series; American Chemical Society: Washington, DC, 2004. 125. Soai, K.; Matsumoto, A.; Kawasaki. T. Asymmetric Autocatalysis and the Origins of Homochirality of Organic Compounds. An Overview. In Advances in Asymmetric Autocatalysis and Related Topics. Academic Press, 2017. 126. Cronin, J. R.; Pizzarello, S. Enantiomeric Excesses in Meteoritic Amino Acids. Science 1997, 275, 951-955. 127. Cronin, J. R.; Pizzarello, S. Amino Acid Enantiomer Excesses in Meteorites: Origin and Significance. Adv. Space Res. 1999, 23, 293-299. 128. Pizzarello, S. The Chemistry of Life's Origin: A Carbonaceous Meteorite Perspective. Acc. Chem. Res. 2006, 39, 231-237. 129. Hawbaker, N. A.; Blackmond, D. G. Rationalization of Asymmetric Amplification via Autocatalysis Triggered by Isotopically Chiral Molecules. ACS Cent. Sci. 2018, 4, 776780.


Page 57 of 58

130. We have strong feeling that possible contribution of dynamic nonlinear effects may have been overlooked or ignored as unimportant in many cases, mostly focusing on improving chemical and optical yields of their stereoselective reactions. 131. The conjecture on the extraterrestrial primary chirality protosource simply pushes the overall question one step back rather than gives a kind of understanding.

Graphical Abstract

80 60

Product ee (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Catalysis

40 20 0 –20 –40 –60

0

20

40

60

80

substrate conversion (%)


100

ACS Catalysis

80 60

Product ee (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

40 20 0 –20 –40 –60

0

20

40

60

80

100

substrate conversion (%)

ACS Paragon Plus Environment

Page 58 of 58

Dynamic Nonlinear Effects in Asymmetric Catalysis - American

Recommend Documents