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Copper-catalyzed radical acyl-cyanation of alkenes with mechanistic studies on the tert-butoxy radical Yihang Jiao, Mong-Feng Chiou, Yajun Li, and Hongli Bao ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.9b01060 • Publication Date (Web): 01 May 2019 Downloaded from http://pubs.acs.org on May 2, 2019
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ACS Catalysis
Copper-catalyzed radical acyl-cyanation of alkenes with mechanistic studies on the tert-butoxy radical Yihang Jiao,†,‡,§ Mong-Feng Chiou,†,§ Yajun Li† and Hongli Bao*,†,‡ †State
Key Laboratory of Structural Chemistry, Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Center for Excellence in Molecular Synthesis, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences, 155 Yangqiao Road West, Fuzhou, Fujian 350002, People’s Republic of China ‡University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China ABSTRACT: A copper-catalyzed radical acyl-cyanation of alkenes with aldehydes, employing TBHP as an initiator has been developed and is reported in this study. Mechanistic studies support the radical pathway of the reaction, which starts from a tert-butoxy radical. Theoretical studies with DFT calculations and our experimental results suggest that metal species is the dominant factor for the β-Me scission of Ot-Bu radical rather than temperature, and the β-Me scission of a free Ot-Bu radical is concentration-dependent kinetically unfavorable in the presence of aldehydes in this reaction.
KEYWORDS Copper-catalyzed, acyl-cyanation, TBHP, tert-butoxy radical, DFT calculation, β-Me scission
Difunctionalization of alkenes receives much attention from chemists because of its step economy which enables simultaneous installation of two functional groups onto a C=C bond in a single process.1 Hydroacylation of alkenes is an important method with which to synthesize unsymmetrical ketones, and has been applied widely in the transformation of alkenes.2 However, introduction of a carbonyl and another functional group such as a nitrile onto the C=C bond of alkenes in a one-pot reaction3 would be a valuable method of alkene difunctionalization but remains a challenge. Acylation of alkenes via a radical pathway is a rapid and convenient method to transform alkenes into functional ketone derivatives.3a,4 Aldehydes are often employed as a source of acyl radicals in acylation reactions. In the presence of a radical initiator or light irradiation, aldehydes can produce acyl radicals which initiate other reactions.3a,4at Recently, acyl-cyclization via the acyl radical pathway was developed by the groups of J.-H. Li,4j Z. Li,4l Wallentin,4v,4w Xu,4y,4z Hsu,4p and F. Li4q. Efforts on intermolecular radical acyl-functionalizations of alkenes have also been reported. For examples, Li et al. stated that β-peroxy ketones can be obtained from vinyl arenes and aldehydes with an ironcatalyzed acylation in the presence of tert-butyl hydroperoxide as an initiator.4f Copper-catalyzed oxidative coupling of alkenes with aldehydes leading to α,βunsaturated ketones was disclosed by Lei et al.4i Subsequently, a vanadyl species as a catalyst that can trigger the acylation of styrenes to form either βhydroxycarbonyl or β-peroxycarbonyl compounds was also reported by Chen et al.4o The cyano group, on the other hand, is an important functional group, frequently found in bioactive natural products and pharmaceuticals, and is a versatile building block which can be easily transformed
into various derivatives such as amides and amines.5 Due to the special behavior of the cyano group, employing such a group in the difunctionalization of alkenes6 and in heterocyclization reactions7 has also been examined. tert-Butoxy-containing peroxides such as di-tert-butyl peroxide (DTBP), tert-butylperoxybenzoate (TBPB), and tert-butyl hydroperoxide (TBHP) are commercially available and inexpensive reagents which play versatile roles and are frequently used in organic synthesis. They generally serve as precursors of the tert-butoxyl radical.4f,4hl,8 As an initiator, the tert-butoxyl radical generated from these peroxides can be used to promote various radical reactions. The usual role of tert-butoxyl radical in this context is to act as a hydrogen extractor in most of the reactions, forming tert-butanol.4f,4h-l,8a-p Occasionally, these peroxides also serve as a source of the methyl radical by further decomposition of the tert-butoxyl radical, named βMe scission,8q-x as has been reported by Yu,8q Hartwig,8u,8v Zu,8w and our group.4t,8r-t The crucial details of the selective conversion of the tert-butoxyl radical to a methyl radical are still however unclear. Although, based on experimental results, the catalysts and temperature might be involved in the formation of the methyl radical, no further investigation on the factor of splitting has been reported, to the best of our knowledge. Herein, we disclose a copper-catalyzed radical acylcyanation of alkenes, affording unsymmetrical β-cyano ketones. In this multicomponent reaction, styrenes are the substrates, trimethylsilyl cyanide (TMSCN) is the source of the cyano group, and aromatic or aliphatic aldehydes serve as the acyl radical source, propagated by the radical initiator, TBHP. In addition, theoretical and experimental studies that were conducted on the reaction mechanism reveal a radical pathway. Furthermore, catalyst and
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temperature - two major factors of tert-butoxyl radical splitting, have been investigated and are discussed in this study. They offer an option for an understanding of the selective splitting of the tert-butoxyl radical to a methyl radical. We initially used the reaction of styrene (1a) with benzaldehyde (2a) and TMSCN (3) as a model to evaluate the scope of the reaction, and examined the metal catalysts, solvents, and ligands (Table 1). Metal catalysts were screened first in dichloromethane (DCM) at 50 oC, and CuCl was found to be most effective, producing the desired product (4aa) in 22% yield (entries 1-9). Several other solvents were tested (entries 10-16), and cyclohexane and methyl tert-butyl ether (MTBE) led to much higher yields than CH3CN and 1,2-dichloroethane (DCE). Using cyclohexane as the solvent, screening of the ligands showed that L3 was the best ligand (entries 17-20). When the loading of the catalyst CuCl and ligand L3 were reduced to 2.5 and 3.5 mol %, respectively, the yield of 4aa increased slightly (entry 21) and was further improved (up to 78% yield), when the reaction was conducted in MTBE instead of cyclohexane (entry 22). Table 1. Optimization of the reaction conditionsa
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desired products (4ba-4la) were obtained in moderate to good yields. Electron-donating and electron-withdrawing groups, including the alkyl group (4ba-4ea), halide (4fa4ha), alkoxyl group (4ia), ester (4ja, 4ka), and phenyl group (4la) were tolerated. Under the same conditions, 2vinylnaphthalene reacted with benzaldehyde, giving the expected product (4ma) in 65% yield, but the α-substituted styrene gave a low yield of the corresponding product (4na). The reaction of a vinylthiazole derivative under the same conditions provided the product (4oa) in a satisfactory yield. Conjugated dienes and α,β-unsaturated carbonyl compounds were also found to be compatible under the reaction conditions, affording the desired products (4pa, 4qa). The method can also be used for the acyl-cyanation of a natural product derivative, producing the corresponding product 4ra in 71% yield.
+
Ph
1a
+
O 2a
Ph
3 O Br
N
N
N
L1
N
O
CN
4aa
L2
N
N
L3
L4
O
O
solvent
ligand
yield (%)b
1
CuCl
DCM
L1
22
2
CuBr
DCM
L1
10
3
CuI
DCM
L1
< 10
4
CuTc
DCM
L1
< 10
5
Cu(MeCN)4PF6
DCM
L1
18
6
CuOAc
DCM
L1
14
7
CuCl2
DCM
L1
10
8
Cu(OAc)2
DCM
L1
16
9
CuC2O4
DCM
L1
16
10
CuCl
none
L1
20
11
CuCl
DCE
L1
14
12
CuCl
CH3CN
L1
10
13
CuCl
Cyclohexane
L1
50
14
CuCl
Dioxane
L1
28
15
CuCl
MTBE
L1
50
16
CuCl
Toluene
L1
40
17
CuCl
Cyclohexane
L2
44
18
CuCl
Cyclohexane
L3
64
19
CuCl
Cyclohexane
L4
44
20
CuCl
Cyclohexane
L5
24
21c
CuCl
Cyclohexane
L3
66
22c
CuCl
MTBE
L3
78 (72)d
1a (0.5 mmol), 2a (2.5 mmol), 3 (1.0 mmol), TBHP (1.25 mmol), cat (5 mol %), ligand (7 mol %), solvent (1 mL), 50 oC, 12 h. b 1H NMR yield. c Cat. (2.5 mol %), ligand (3.5 mol %). d Isolated yield in parentheses.
CN
O
CN
Ph
O
CN
O
CN H
O
O
Ph 4ma, 65%
4la, 71%
Ph
O
H H
O 4pa, 38% Z:E = 2/1
O
4ia, 68%
MeO
Ph
S 4oa, 86%
4na, 38%
NC
catalyst
CN
4ha, 69%
Br
O
CN
Ph 4ea, 53%
Ph
4ka, 64%
AcO
O
O
Ph
N
L5
entry
CN
CN
4ja, 71%
N
N
O
Ph MeOOC
CN
Ph 4da, 70%
4ga, 65%
Cl
Ph
4
O
Ph
4fa, 60%
CN
N
CN Ph
Br N
CN
4ca, 76%
O
Ph
O
O Ph
t-Bu
CN
R
TBHP (2.5 equiv), MTBE 50 oC, 12 h CN
4ba, 65%
O
CN
Reaction Conditions
TMSCN
CN
O
CN
CuCl (2.5 mol %), L3 (3.5 mol %)
Ph
F
Ph
1
+ Ph O + TMSCN 2a 3
R
4ra, 71%c
O
O 4qa, 25%
1 (0.5 mmol), 2a (2.5 mmol), 3 (1.0 mmol), TBHP (1.25 mmol), MTBE (1 mL), 50 oC, 12 h. b Isolated product. c 1r (0.3 mmol), 2a (1.5 mmol), 3 (0.6 mmol), TBHP (0.75 mmol), MTBE (0.6 mL), 50 oC, 12 h. a
Scheme 1. Substrate scope of alkenes for acylcyanation.a,b CN + 1a CN
Aryl
O + TMSCN 2 3 CN
O
CuCl (2.5 mol %), L3 (3.5 mol %)
4ab, 75% CN
O
CN
CN
Ph
t-Bu
CN
OMe
4aj, 50%c CN O
CN
CN
Cl
CN
CN
CN
OH
CN
4al, 38%
S
O
4ao, 40%
CF3 4ai, 45%
F
O
CN Ph
TMS
O
Ph
O
Ph
Ph 4an, 52%
CN F
Ph
4ak, 42%
O
4ae, 72%
O
4ah, 61%
O
Ph
Ph
CN Ph
Ph
4ag, 65%
O
Ph
O
4ad, 60%
O
Ph
4af, 56%
4
Ph
4ac, 70%
O
Aryl
TBHP (2.5 equiv), MTBE 50 oC, 12 h
Ph
Ph
O
Ph
4ap, 54%
4am, 70% NC
O O
O
Ph
S
4aq, 47%
1a (0.5 mmol), 2 (2.5 mmol), 3 (1.0 mmol), TBHP (1.25 mmol), MTBE (1 mL), 50 oC, 12 h. b Isolated product. c DCM was used in stead of MTBE. a
Scheme 2. Substrate scope of aromatic aldehydes for acyl-cyanation.a,b
a
The scope of alkenes was then investigated under the optimized reaction conditions (Scheme 1). Monosubstituted styrenes were first examined, and the
Inspired by these promising results, we next focused on the scope of aromatic aldehydes. Various functional-group substituted benzaldehydes were compatible (Scheme 2) and benzaldehydes with substituents such as alkyl, alkoxyl,
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ACS Catalysis halide, cyano, hydroxyl, methylthio, and trofluoromethyl, all produced the desired products (4ab-4al) in moderate to good yields. The reaction of 2-naphthaldehyde with styrene produced the corresponding product (4am) in 70% yield and 4-((trimethylsilyl)-ethynyl)benzaldehyde and phenylpropiolaldehyde were also compatible under the reaction conditions resulting in products 4an and 4ao, respectively. In addition, aldehydes with a heterocyclic ring provided products (4ap, 4aq) in moderate yields. Encouraged by the success of reactions employing aromatic aldehydes, we then investigated aliphatic aldehydes and obtained the results summarized in Scheme 3. The reactions of various aliphatic aldehydes with styrene (1a) proceeded smoothly under the standard conditions to give the corresponding products in moderate to good yields. Aliphatic aldehydes with functional groups, including the βarylalkyl aldehyde (4ar), naphthenic aldehydes (4as, 4at), saturated alkyl aldehydes (4au, 4av) and unsaturated alkyl aldehydes (4aw, 4ax), performed well under the reaction conditions.
CN
CuCl (2.5 mol %), L3 (3.5 mol %) +
Alkyl
1a
CN
2
O + TMSCN 3
O
CN
CN
Alkyl
Ph
TBHP (2.5 equiv), MTBE 50 oC, 12 h
O
O 4
O
CN
O
Ph 4ar, 68%
4as, 76% CN
4at, 59%
O
CN
O
4au, 46% CN
O
8 4av, 88%
4aw, 76%
4ax, 70%
a 1a (0.5 mmol), 2 (2.5 mmol), 3 (1.0 mmol), TBHP (1.25 mmol), MTBE (1 mL), 50 oC, 12 h. b Isolated product.
Scheme 3. Substrate scope of aliphatic aldehydes for acyl-cyanation.a,b
a) Hydrolysis of the cyano group CN
H 2N
O
O
conc. H2SO4
O
rt 5, 71%
4aa b) Synthesis of oxime CN
O
NH2OH•HCl (1.0 equiv) NaOH (62.5 mol %) H2O (3 equiv)
CN
N
OH
EtOH (0.6 mL), 60 oC 6, 62%
4aa c) Reduction of the ketone CN O
NaBH4 (1.2 equiv)
CN
OH
MeOH (0.5 mL), 0 oC 4aa
7, 63%, dr = 3.9/1
Scheme 4. Further transformations of acyl-cyanation products. Further transformations of the acyl-cyanation products were then explored to showcase the value of this method (Scheme 4). The acyl-cyanation product (4aa) can be converted into the corresponding amide (5) in 71% yield under conditions including concentrated sulfuric acid. On the other hand, product 4aa can participate in a condensation reaction with hydroxylamine hydrochloride to produce an oxime (6) which is a structural motif present
in many materials. In addition, with a reducing agent, the carbonyl group in 4aa can be reduced to an alcohol (7).
a) Radical Trapping Experiment with TEMPO H + TMSCN R O 1a 3 2a or 2s R = Ph or Cy b) Radical Trapping Experiment with BHT +
Ph
O + TMSCN
1a
2s
Ph R 4aa or 4as No product
TEMPO (1.5 equiv )
H +
Ph
Standard Conditions BHT (1.5 equiv ) Ph
3
CN
O
CN
Standard Conditions
Cy 4as, trace
O
t-Bu
O
Cy HO t-Bu
8, 28%
c) Isotope-labeling study D
+
Ph
Ph
1a
O 2a-D
+ TMSCN
CuCl (2.5 mol %) L3 (3.5 mol %) TBHP (1.25 equiv) MTBE, 50 oC, 30 min
3
O
d) Radical Clock Experiment Ph
Ph
Ph
O + TMSCN
+ Ph
Standard Conditions
O Ph
10
2a
D
9 detected by GC-MS
3
Ph 11, 58% CN
Scheme 5. Mechanistic Studies Some preliminary experiments were performed to explore the mechanism of the reaction (Scheme 5). A radical trapping experiment was first conducted to support the proposed radical pathway. Radical scavengers, such as 2,2,6,6-tetramethyl-1-piperidinyloxy) (TEMPO) and butylated hydroxytoluene (BHT) were introduced into the standard reactions employing 2a and 2s, respectively, and no desired products 4aa and 4as were produced in either reaction (Schemes 5a and 5b). Instead, compound 8 was detected by GC-MS analysis and isolated in 28% yield (Scheme 5b). The results indicated that the acyl-cyanation reaction proceeds in a radical pathway and the reaction can be effectively interrupted by radical scavengers. Because of the lack of desired products (i.e. 4aa and 4as) and the lack of corresponding acyl radical trapped by TEMPO, it is worth to note that reactions in the presence of TEMPO may be also associated with a direct reaction of TEMPO with the copper catalyst.9 To identify the radical species which abstracts the H-atom from the aldehyde, deuterated benzaldehyde (2aD) was synthesized and subjected to the reaction with styrene (1a) under the standard conditions. It was found that deuterated tert-butanol (9) was the major deuterated compound that could be detected in GC-MS analysis in the first 30 minutes (Scheme 5c). A radical clock compound (10), bearing a cyclopropylmethyl moiety, was also employed in the reaction to further support the hypothesis of the radical path. As expected, the ring-opened product (11) was obtained in a yield of 58% (Scheme 5d). Although the reaction can be suppressed by TEMPO and BHT, the methyl radical may not be separated easily from the tert-butoxyl radical under the reaction conditions. This contrasts with our previous studies on iron-catalyzed acylation in which a certain amount of 1-methoxy-2,2,6,6tetramethyl-piperidine was detected by GC-MS analysis.4t Since the reaction pathway initiated by the tert-butoxyl radical was established by the experimental studies above, DFT calculations were performed on the copper-catalyzed inner sphere single-electron transfer (SET) processes of TBHP and a subsequent series of radical relay pathways were carried out in an effort to understand the mechanism
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ACS Catalysis
After investigations on radical relay, the cyanation of benzyl radical are then explored. Since the hydroxyl copper(II) complex Int1 is the favorable intermediate rather than Int1’; in addition, the trimethylsilanol (TMSOH) can be observed in GC-MS analysis, the trimethylsilyl exchange of TMSCN with Int1 is therefore computed. A transition state of TMS exchange, TS9, is located with a barrier of 17.8 kcal/mol, and then, interestingly, leads to a exergonic cyanocopper(II) complex (Int5) rather than a isocyanocopper(II) complex. Further discussion of the cyanocopper(II) complex formation is reported in Supporting Information with some geometrical parameters of TS9 and the intrinsic reaction coordinate (IRC) path (Figure S1) for comparison to the isocynocopper(II) complex formation in our previous study.6h Since the
isocyanocopper complex is not propagated directly from a hydroxyl copper(II) complex, an (a)
N Cu
G / kcal mol-1
N TS1
N
Cl
Cu O
O H
Cl
N
O
H2N
N
TS1'
Cl
Cu OH
TS4 40.0
CH3
O TS4
Br N
N =
TS1' 19.8
N
N Br
TS1 10.6
Int2 = Ot-Bu, Int2' = OH
Int1' 9.3
N
Int2'
Cu N
LCuCl 0.0
O
N
Int1 -8.0
Int2
Cu N Int1
O
O
Ph
H
O
TS2
H CH2
TS7 -Me scission TS6 11.8 TS5 9.3
Ph
H
Ph
O
OH
O O
Ph
Ph
TS6 TS5 hydrogen extraction from styrene
TS8
Ph Ph TS8 4.3
TS7 1.9 TS2 0.5
Int2 -8.0
Cl
Cu-catalyzed -Me scission
TBHP O-O bond cleavage induced by SET from Cu(I)
(b)
Cl
Int1' TBHP
G / kcal mol-1
at the atomic level (Figure 1). Initially, the copper catalyst, LCuCl (L = 4,4'-dibromo-2,2'-bipyridine, L3), is considered to be the active species which is oxidized by TBHP to result in a Cu(II) complex appended with a hydroxyl (Int1) and a tert-butoxyl radical (Int2). The free energy barrier of this inner sphere SET process is only 10.6 kcal/mol (TS1). The other inner sphere SET pathway leading to a Cu(II)Ot-Bu complex (Int1’) with a hydroxyl radical (Int2’) has also been considered (Figure 1a), but it is a kinetically disfavored and thermodynamically unfavorable pathway in which the energy barrier of TS1’ is 9.2 kcal/mol higher than that of TS1. Furthermore, copper-catalyzed β-Me scission from the Cu(II)Ot-Bu complex (Int1’), faces a quite high barrier of 30.7 kcal/mol (TS4), indicating that Cu(II) species cannot assist the methyl radical splitting. In contrast, some previous reports of iron-catalyzed reactions involving tert-butoxy-containing peroxides stated that the methyl radical can be propagated at the same, or even a lower temperature implying that the dominant factor of β-Me scission may be the catalyst rather than the temperature.4t,8r,8t However, it may be worth noting that fragmentation of O-radicals by using other catalysts8r-t or photo catalysis10 under moderate condition is also a useful mechanistic tool for further radical cascades.11 Next, we focused on the series of free tert-butoxyl radical relay pathways. Figure 1b depicts the hydrogen extraction, β-Me scission and β-addition pathways of Int2. Upon comparison, hydrogen extraction from benzaldehyde (2a) is seen to be the most kinetically favorable pathway. The energy barrier of TS2 is only 8.5 kcal/mol, much less than that of TS5 and TS6 (17.3 and 19.8 kcal/mol, respectively). Subsequently, an acyl radical (Int3) is then generated in situ with a exergonicity of 11.6 kcal/mol. An acyl radical undergoes a β-addition process with 1a to form a benzyl radical, (Int4) in a step that is exergonic by 10.8 kcal/mol and has a barrier of 12.9 kcal/mol (TS3). On the other hand, the energy barrier of β-Me scission (TS7) in a free Ot-Bu radical is 9.9 kcal/mol, somewhat higher than that of TS2. Owing to the twofold equivalent of aldehyde to TBHP and low catalyst loading (2.5 mol%), this result indicates that methyl radical generation may be concentration-dependent kinetically unfavorable in the presence of the large quantity of aldehyde than Ot-Bu radical. The β-Me scission pathway however, may be a competitive process at a higher temperature.8q,8u-w Moreover, radical Int2 addition onto 1a was also considered, but turns out to be a kinetically unfavorable process (TS8) with much higher barrier of 12.3 kcal/mol.
Ph
O
TS3 -addition onto styrene
TS3 -6.7
O
O
Ph 2a
Ph
H
Int3 -19.6
t-BuOH
Int2
O Ph Int3
Ph Ph
O
Int4 -30.4
Int4
(c)
N Cl Cu N OH N C Si
N Ph Cl Cu N C O Ph N 3 TS10
TS9
G / kcal mol-1
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
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Ph Cl N Ph Cu N C O N 3,1 MECP
TS9 9.8
Int1 -8.0
TMSCN
TS10 -3.1
3,1
MECP -17.5
TMSOH Int5 -29.2
3
3 Int6 -31.2
Int4' N Cu N
Cl OH
N Cu N
Int1
CN Int5
TMS Exchange
Cl
LCuCl Ph Cl N Cu Ph N O CN 3
Int6
Ph Ph
NC
LCuCl
P -63.3
O P Cyanation of Benzyl Radical
Figure 1. Gibbs free energy profiles for (a) the copper-catalyzed inner sphere SET processes of TBHP, (b) series of radical relay pathways and (c) the cyanation of benzyl radical via cyanocopper(II) complex.
inner-sphere Cu(III) mechanism6c,6g,7a,7c for cyanation is therefore considered. However, no transition state corresponding to Cu(III) species formation can be located (See “Discussions on the TMS exchange and the cyano group transfer for product formation” and Figure S2, S3 in SI for more details). Instead of the inner-sphere Cu(III) mechanism, an outer-sphere cyanide transfer via a minimum energy crossing point (MECP), 3,1MECP, is found. The electronic energy of 3,1MECP is estimated to be 13.7 kcal/mol higher than that of 3Int6, a benzyl radical approaching to a cyanocopper(II) complex. After spin crossing, a dramatically exergonic product formation (-63.6 kcal/mol) along a steeply downhill potential energy surface (PES) can be found (See Figure S4). A triplet
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ACS Catalysis cyanation TS (3TS10) corresponding to C-C bond coupling is also located, however, with a much higher barrier (28.1 kcal/mol).
AUTHOR INFORMATION
Based on these experimental and theoretical mechanistic studies, a catalytic mechanism is proposed for this acylcyanation reaction and is shown in Scheme 6. Initially, a ligated copper(I) catalyst (A) and TBHP undergoes a inner sphere SET process to afford a Cu(II) species (B) and a OtBu radical. Then, the Ot-Bu radical extracts a hydrogen atom from the aldehyde to propagate an acyl radical (C) and a molecule of tert-butanol. Subsequently, the acyl radical captures a vinylarene to form a more stable benzyl radical (E). Upon ligand exchange with TMSCN, the Cu(II) species B converts to a cyanocopper complex (D). The cyanocopper(II) species, D, then undergo cyano group transfer with the benzyl radical E to access the acylcyanation product (4) via an outer-sphere cyano group transfer pathway through an outer-sphere electron transfer crossing point (F), meanwhile regenerating the copper(I) catalyst A. The methyl radical is absent in this proposed mechanism due to the low temperature and the copper catalyst which cannot assist the β-Me scission of tertbutoxyl radical.
*
[email protected] CN
O
Ar
O LCu(I)
R
O
H
A
4
SET
LCu(II)
O O
C N LCu(II)OH B
O
Ar F
R
D
R TMSCN LCu(II)CN
O Ar
D R
E
OD
TMSOH GC-MS
radical scavengers & radical clock
isotope labeling
O R
C Ar
Scheme 6. Proposed catalytic cycle for the acylcyanation reaction. In summary, the copper-catalyzed radical acyl-cyanation of alkenes has been established to access various unsymmetrical β-cyano ketones with versatile functional groups. Aromatic aldehydes and aliphatic aldehydes can be successfully used as the acyl source in this radical reaction. In addition, substituents on the styrenes have been demonstrated to be tolerant in these reaction conditions. Mechanistic studies suggest the involvement of a propagated acyl radical which is initiated by a tert-butoxyl radical. In addition, the results of DFT calculations are consistent with our experimental observation that the free Ot-Bu radical can be generated from TBHP by a coppercatalyzed reaction; however, methyl radical propagation via β-Me scission of the Ot-Bu radical may not be assisted by copper catalysis, and is even an unfavorable pathway in the presence of the large quantity of aldehyde. Theoretical studies incorporating the mechanistic studies in this paper are expected to shed some light on the metal-catalyzed reactions involved tert-butoxyl-containing peroxides.
ASSOCIATED CONTENT
Corresponding Author Author Contribution §Y.
Jiao and M.-F. Chiou contributed equally.
ORCID Mong-Feng Chiou: 0000-0001-7074-9285 Yajun Li: 0000-0001-6690-2662 Hongli Bao: 0000-0003-1030-5089
Notes
The authors declare no competing financial interest. Supporting Information Experimental procedures, characterization of new compounds, synthetic applications, mechanistic studies, NMR spectra, theoretical studies (PDF). Correspondence and requests for materials should be addressed to H. B. This material is available free of charge via the Internet at http://pubs.acs.org.
ACKNOWLEDGMENT We thank the National Key R&D Program of China (2017YFA0700103), the NSFC (Grant Nos 21672213, 21871258), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB20000000), and the Haixi Institute of CAS (Grant No. CXZX-2017-P01) for financial support.
REFERENCES (1) (a) Beccalli, E. M.; Broggini, G.; Martinelli, M.; Sottocornola, S. CC, C-O, C-N Bond Formation on Sp2 Carbon by Pd(II)-Catalyzed Reactions Involving Oxidant Agents. Chem. Rev. 2007, 107, 53185365; (b) Jensen, K. H.; Sigman, M. S. Mechanistic Approaches to Palladium-Catalyzed Alkene Difunctionalization Reactions. Org. Biomol. Chem. 2008, 6, 4083-4088; (c) Bataille, C. J.; Donohoe, T. J. Osmium-Free Direct Syn-Dihydroxylation of Alkenes. Chem. Soc. Rev. 2011, 40, 114-128; (d) McDonald, R. I.; Liu, G.; Stahl, S. S. Palladium(II)-Catalyzed Alkene Functionalization Via Nucleopalladation: Stereochemical Pathways and Enantioselective Catalytic Applications. Chem. Rev. 2011, 111, 2981-3019; (e) Romero, R. M.; Woste, T. H.; Muniz, K. Vicinal Difunctionalization of Alkenes with Iodine(III) Reagents and Catalysts. Chem. Asian. J. 2014, 9, 972-983; (f) Besset, T.; Poisson, T.; Pannecoucke, X. Direct Vicinal Difunctionalization of Alkynes: An Efficient Approach Towards the Synthesis of Highly Functionalized Fluorinated Alkenes. Eur. J. Org. Chem. 2015, 2015, 2765-2789; (g) Yin, G.; Mu, X.; Liu, G. Palladium(II)-Catalyzed Oxidative Difunctionalization of Alkenes: Bond Forming at a High-Valent Palladium Center. Acc. Chem. Res. 2016, 49, 2413-2423. (2) (a) Jun, C.-H.; Jo, E.-A.; Park, J.-W. Intermolecular Hydroacylation by Transition-Metal Complexes. Eur. J. Org. Chem. 2007, 2007, 1869-1881; (b) Willis, M. C. Transition Metal Catalyzed Alkene and Alkyne Hydroacylation. Chem. Rev. 2010, 110, 725-748; (c) Biju, A. T.; Kuhl, N.; Glorius, F. Extending Nhc-Catalysis: Coupling Aldehydes with Unconventional Reaction Partners. Acc. Chem. Res. 2011, 44, 1182-1195; (d) Leung, J. C.; Krische, M. J. Catalytic Intermolecular Hydroacylation of C–C Π-Bonds in the Absence of Chelation Assistance. Chem. Sci. 2012, 3, 2202; (e) Murphy, S. K.; Park, J. W.; Cruz, F. A.; Dong, V. M. Organic Chemistry. Rh-Catalyzed C-C Bond Cleavage by Transfer Hydroformylation. Science 2015, 347, 56-60. (3) (a) Punniyamurthy, T.; Bhatia, B.; Iqbal, J. Cobalt(II)-Catalyzed Reaction of Enolizable Aldehydes with Alkenes in the Presence of Dioxygen: The Role of Acyl Radical. J. Org. Chem. 1994, 59, 850-853;
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(b) Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Catalytic Markovnikov and Anti-Markovnikov Functionalization of Alkenes and Alkynes: Recent Developments and Trends. Angew. Chem. Int. Ed. 2004, 43, 3368-3398; (c) Schiesser, C. H.; Wille, U.; Matsubara, H.; Ryu, I. Radicals Masquerading as Electrophiles: Dual Orbital Effects in Nitrogen-Philic Acyl Radical Cyclization and Related Addition Reactions. Acc. Chem. Res. 2007, 40, 303-313; (d) Cernak, T. A.; Lambert, T. H. Multicatalytic Synthesis of Α-Pyrrolidinyl Ketones Via a Tandem Palladium(II)/Indium(III)-Catalyzed Aminochlorocarbonylation/Friedel−Crafts Acylation Reaction. J. Am. Chem. Soc. 2009, 131, 3124-3125; (e) Taniguchi, T.; Sugiura, Y.; Zaimoku, H.; Ishibashi, H. Iron-Catalyzed Oxidative Addition of Alkoxycarbonyl Radicals to Alkenes with Carbazates and Air. Angew. Chem. Int. Ed. 2010, 49, 10154-10157. (4) (a) Macias, F. A.; Molinillo, J. M. G.; Collado, I. G.; Massanet, G. M.; Rodriguez-Luis, F. “An Efficient and Mild Entry to 1,4-Dicarbonyl Compounds Via Photochemical Addition of Acyl Radical to Electron-Deficient Olefins”. Tetrahedron Lett. 1990, 31, 30633066; (b) Macías, F. A.; Molinillo, J. M. G.; Massanet, G. M.; Rodríguez-Luis, F. Study of Photochemical Addition of Acyl Radical to Electron-Deficient Olefins. Tetrahedron 1992, 48, 3345-3352; (c) Yoshikai, K.; Hayama, T.; Nishimura, K.; Yamada, K.; Tomioka, K. Thiol-Catalyzed Acyl Radical Cyclization of Alkenals. J. Org. Chem. 2005, 70, 681-683; (d) Esposti, S.; Dondi, D.; Fagnoni, M.; Albini, A. Acylation of Electrophilic Olefins through DecatungstatePhotocatalyzed Activation of Aldehydes. Angew. Chem. Int. Ed. 2007, 46, 2531-2534; (e) Chudasama, V.; Fitzmaurice, R. J.; Caddick, S. Hydroacylation of Alpha,Beta-Unsaturated Esters Via Aerobic C-H Activation. Nat. Chem. 2010, 2, 592-596; (f) Liu, W.; Li, Y.; Liu, K.; Li, Z. Iron-Catalyzed Carbonylation-Peroxidation of Alkenes with Aldehydes and Hydroperoxides. J. Am. Chem. Soc. 2011, 133, 10756-10759; (g) Matcha, K.; Antonchick, A. P. MetalFree Cross-Dehydrogenative Coupling of Heterocycles with Aldehydes. Angew. Chem. Int. Ed. 2013, 52, 2082-2086; (h) Leifert, D.; Daniliuc, C. G.; Studer, A. 6-Aroylated Phenanthridines Via Base Promoted Homolytic Aromatic Substitution (Bhas). Org. Lett. 2013, 15, 6286-6289; (i) Wang, J.; Liu, C.; Yuan, J.; Lei, A. CopperCatalyzed Oxidative Coupling of Alkenes with Aldehydes: Direct Access to Α,Β-Unsaturated Ketones. Angew. Chem. Int. Ed. 2013, 52, 2256-2259; (j) Zhou, M.-B.; Song, R.-J.; Ouyang, X.-H.; Liu, Y.; Wei, W.-T.; Deng, G.-B.; Li, J.-H. Metal-Free Oxidative Tandem Coupling of Activated Alkenes with Carbonyl C(Sp2)–H Bonds and Aryl C(Sp2)–H Bonds Using Tbhp. Chem. Sci. 2013, 4, 2690-2694; (k) Zhao, J.; Li, P.; Xia, C.; Li, F. Direct N-Acylation of Azoles Via a MetalFree Catalyzed Oxidative Cross-Coupling Strategy. Chem. Commun. 2014, 50, 4751-4754; (l) Lv, L.; Lu, S.; Guo, Q.; Shen, B.; Li, Z. IronCatalyzed Acylation-Oxygenation of Terminal Alkenes for the Synthesis of Dihydrofurans Bearing a Quaternary Carbon. J. Org. Chem. 2015, 80, 698-704; (m) Li, J.; Wang, D. Z. Visible-LightPromoted Photoredox Syntheses of Alpha,Beta-Epoxy Ketones from Styrenes and Benzaldehydes under Alkaline Conditions. Org. Lett. 2015, 17, 5260-5263; (n) Wei, W.-T.; Yang, X.-H.; Li, H.-B.; Li, J.-H. Oxidative Coupling of Alkenes with Aldehydes and Hydroperoxides: One-Pot Synthesis of 2,3-Epoxy Ketones. Adv. Synth. Catal. 2015, 357, 59-63; (o) Yang, W. C.; Weng, S. S.; Ramasamy, A.; Rajeshwaren, G.; Liao, Y. Y.; Chen, C. T. Vanadyl Species-Catalyzed Complementary Beta-Oxidative Carbonylation of Styrene Derivatives with Aldehydes. Org. Biomol. Chem. 2015, 13, 2385-2392; (p) Hsu, D.-S.; Chen, C.-H.; Hsu, C.-W. Synthesis of Spiranes by Thiol-Mediated Acyl Radical Cyclization. Eur. J. Org. Chem. 2016, 2016, 589-598; (q) Zhao, J.; Li, P.; Li, X.; Xia, C.; Li, F. Straightforward Synthesis of Functionalized Chroman-4-Ones through Cascade Radical Cyclization-Coupling of 2(Allyloxy)Arylaldehydes. Chem. Commun. 2016, 52, 3661-3664; (r) Mukherjee, S.; Garza-Sanchez, R. A.; Tlahuext-Aca, A.; Glorius, F. Alkynylation of Csp2 (O)-H Bonds Enabled by PhotoredoxMediated Hydrogen-Atom Transfer. Angew. Chem. Int. Ed. 2017, 56, 14723-14726; (s) Vu, M. D.; Das, M.; Liu, X. W. Direct Aldehyde Csp(2) -H Functionalization through Visible-Light-Mediated
Photoredox Catalysis. Chem. Eur. J. 2017, 23, 15899-15902; (t) Ge, L.; Li, Y.; Bao, H. Iron-Catalyzed Radical Acyl-Azidation of Alkenes with Aldehydes: Synthesis of Unsymmetrical Β-Azido Ketones. Org. Lett. 2019, 21, 256-260; (u) Boger, D. L.; Mathvink, R. J. Intramolecular Acyl Radical-Alkene Addition Reactions: Macrocyclization Reactions. J. Am. Chem. Soc. 1990, 112, 40084011; (v) Bergonzini, G.; Cassani, C.; Wallentin, C. J. Acyl Radicals from Aromatic Carboxylic Acids by Means of Visible-Light Photoredox Catalysis. Angew. Chem. Int. Ed. 2015, 54, 1406614069; (w) Bergonzini, G.; Cassani, C.; Lorimer-Olsson, H.; Horberg, J.; Wallentin, C. J. Visible-Light-Mediated Photocatalytic Difunctionalization of Olefins by Radical Acylarylation and Tandem Acylation/Semipinacol Rearrangement. Chem. Eur. J. 2016, 22, 3292-3295; (x) Dong, S.; Wu, G.; Yuan, X.; Zou, C.; Ye, J. Visible-Light Photoredox Catalyzed Hydroacylation of Electron-Deficient Alkenes: Carboxylic Anhydride as an Acyl Radical Source. Org. Chem. Front. 2017, 4, 2230-2234; (y) Li, C. G.; Xu, G. Q.; Xu, P. F. Synthesis of Fused Pyran Derivatives Via Visible-Light-Induced Cascade Cyclization of 1,7-Enynes with Acyl Chlorides. Org. Lett. 2017, 19, 512-515; (z) Xu, S.-M.; Chen, J.-Q.; Liu, D.; Bao, Y.; Liang, Y.-M.; Xu, P.-F. Aroyl Chlorides as Novel Acyl Radical Precursors Via Visible-Light Photoredox Catalysis. Org. Chem. Front. 2017, 4, 1331-1335; (aa) Lan, X.-W.; Wang, N.-X.; Xing, Y. Recent Advances in Radical Difunctionalization of Simple Alkenes. Eur. J. Org. Chem. 2017, 2017, 5821-5851. (5) (a) F. Fleming, F. Nitrile-Containing Natural Products. Nat. Prod. Rep. 1999, 16, 597-606; (b) Enders, D.; Shilvock, J. P. Some Recent Applications of Α-Amino Nitrile Chemistry. Chem. Soc. Rev. 2000, 29, 359-373; (c) Fleming, F. F.; Yao, L.; Ravikumar, P. C.; Funk, L.; Shook, B. C. Nitrile-Containing Pharmaceuticals: Efficacious Roles of the Nitrile Pharmacophore. J. Med. Chem. 2010, 53, 7902-7917; (d) Wang, T.; Jiao, N. Direct Approaches to Nitriles Via Highly Efficient Nitrogenation Strategy through C–H or C–C Bond Cleavage. Acc. Chem. Res. 2014, 47, 1137-1145. (6) (a) Liang, Z.; Wang, F.; Chen, P.; Liu, G. Copper-Catalyzed Intermolecular Cyanotrifluoromethylation of Alkenes: Convenient Synthesis of Cf3-Containing Alkyl Nitriles. J. Fluorine Chem. 2014, 167, 55-60; (b) Wang, F.; Wang, D.; Wan, X.; Wu, L.; Chen, P.; Liu, G. Enantioselective Copper-Catalyzed Intermolecular Cyanotrifluoromethylation of Alkenes Via Radical Process. J. Am. Chem. Soc. 2016, 138, 15547-15550; (c) Zhang, W.; Wang, F.; McCann, S. D.; Wang, D.; Chen, P.; Stahl, S. S.; Liu, G. Enantioselective Cyanation of Benzylic C-H Bonds Via Copper-Catalyzed Radical Relay. Science 2016, 353, 1014-1018; (d) Hassan, H.; Pirenne, V.; Wissing, M.; Khiar, C.; Hussain, A.; Robert, F.; Landais, Y. FreeRadical Carbocyanation of Olefins. Chem. Eur. J. 2017, 23, 46514658; (e) Wang, D.; Wang, F.; Chen, P.; Lin, Z.; Liu, G. Enantioselective Copper-Catalyzed Intermolecular Amino- and Azidocyanation of Alkenes in a Radical Process. Angew. Chem. Int. Ed. 2017, 56, 2054-2058; (f) Liu, J. L.; Zhu, Z. F.; Liu, F. Oxycyanation of Vinyl Ethers with 2,2,6,6-Tetramethyl-N-Oxopiperidinium Enabled by Electron Donor-Acceptor Complex. Org. Lett. 2018, 20, 720-723; (g) Wang, F.; Wang, D.; Zhou, Y.; Liang, L.; Lu, R.; Chen, P.; Lin, Z.; Liu, G. Divergent Synthesis of Cf3 -Substituted Allenyl Nitriles by Ligand-Controlled Radical 1,2- and 1,4-Addition to 1,3Enynes. Angew. Chem. Int. Ed. 2018, 57, 7140-7145; (h) Zhu, X.; Deng, W.; Chiou, M.-F.; Ye, C.; Jian, W.; Zeng, Y.; Jiao, Y.; Ge, L.; Li, Y.; Zhang, X.; Bao, H. Copper-Catalyzed Radical 1,4-Difunctionalization of 1,3-Enynes with Alkyl Diacyl Peroxides and NFluorobenzenesulfonimide. J. Am. Chem. Soc. 2019, 141, 548-559. (7) (a) He, Y. T.; Li, L. H.; Zhou, Z. Z.; Hua, H. L.; Qiu, Y. F.; Liu, X. Y.; Liang, Y. M. Copper-Catalyzed Three-Component Cyanotrifluoromethylation/Azidotrifluoromethylation and Carbocyclization of 1,6-Enynes. Org. Lett. 2014, 16, 3896-3899; (b) Chen, F.; Zhu, F. F.; Zhang, M.; Liu, R. H.; Yu, W.; Han, B. Iminoxyl Radical-Promoted Oxycyanation and Aminocyanation of Unactivated Alkenes: Synthesis of Cyano-Featured Isoxazolines and Cyclic Nitrones. Org. Lett. 2017, 19, 3255-3258; (c) Meng, F.; Zhang, H.; Guo, K.; Dong, J.; Lu, A. M.; Zhu, Y. Access to Cyano-
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ACS Catalysis Containing Isoxazolines Via Copper-Catalyzed Domino Cyclization/Cyanation of Alkenyl Oximes. J. Org. Chem. 2017, 82, 10742-10747. (8) (a) Kochi, J. K.; Mains, H. E. Studies on the Mechanism of the Reaction of Peroxides and Alkenes with Copper Salts*,1. J. Org. Chem. 1965, 30, 1862-1872; (b) Kharasch, M. S.; Sosnovsky, G. The Reactions of T-Butyl Perbenzoate and Olefins—a Stereospecific Reaction1. J. Am. Chem. Soc. 1958, 80, 756-756; (c) Pryor, W. A.; Hendrickson, W. H. Reaction of Nucleophiles with Electron Acceptors by Sn2 or Electron Transfer (Et) Mechanisms: Tert-Butyl Peroxybenzoate/Dimethyl Sulfide and Benzoyl Peroxide/N,NDimethylaniline Systems. J. Am. Chem. Soc. 1983, 105, 7114-7122; (d) Boess, E.; Schmitz, C.; Klussmann, M. A Comparative Mechanistic Study of Cu-Catalyzed Oxidative Coupling Reactions with N-Phenyltetrahydroisoquinoline. J. Am. Chem. Soc. 2012, 134, 5317-5325; (e) Wei, W.-T.; Zhou, M.-B.; Fan, J.-H.; Liu, W.; Song, R.J.; Liu, Y.; Hu, M.; Xie, P.; Li, J.-H. Synthesis of Oxindoles by IronCatalyzed Oxidative 1,2-Alkylarylation of Activated Alkenes with an Aryl C(Sp2)H Bond and a C(Sp3)H Bond Adjacent to a Heteroatom. Angew. Chem. Int. Ed. 2013, 52, 3638-3641; (f) Zhou, S.-L.; Guo, L.-N.; Wang, H.; Duan, X.-H. Copper-Catalyzed Oxidative Benzylarylation of Acrylamides by Benzylic CH Bond Functionalization for the Synthesis of Oxindoles. Chem. Eur. J. 2013, 19, 12970-12973; (g) Cai, Z.-J.; Lu, X.-M.; Zi, Y.; Yang, C.; Shen, L.-J.; Li, J.; Wang, S.-Y.; Ji, S.-J. I2/Tbpb Mediated Oxidative Reaction of N-Tosylhydrazones with Anilines: Practical Construction of 1,4Disubstituted 1,2,3-Triazoles under Metal-Free and Azide-Free Conditions. Org. Lett. 2014, 16, 5108-5111; (h) Chen, C.; Xu, X.-H.; Yang, B.; Qing, F.-L. Copper-Catalyzed Direct Trifluoromethylthiolation of Benzylic C–H Bonds Via Nondirected Oxidative C(Sp3)–H Activation. Org. Lett. 2014, 16, 3372-3375; (i) Wei, W.-T.; Song, R.-J.; Li, J.-H. Copper-Catalyzed Oxidative ΑAlkylation of Α-Amino Carbonyl Compounds with Ethers Via Dual C(Sp3)-H Oxidative Cross- Coupling. Adv. Synth. Catal. 2014, 356, 1703-1707; (j) Tang, S.; Liu, K.; Long, Y.; Gao, X.; Gao, M.; Lei, A. Iodine-Catalyzed Radical Oxidative Annulation for the Construction of Dihydrofurans and Indolizines. Org. Lett. 2015, 17, 2404-2407; (k) Chen, W.; Zhang, Y.; Li, P.; Wang, L. Tert-Butyl Peroxybenzoate Mediated Formation of 3-Alkylated Quinolines from N-Propargylamines Via a Cascade Radical Addition/Cyclization Reaction. Org. Chem. Front. 2018, 5, 855-859; (l) Shen, S.-J.; Zhu, C.-L.; Lu, D.-F.; Xu, H. Iron-Catalyzed Direct Olefin Diazidation Via Peroxyester Activation Promoted by NitrogenBased Ligands. ACS Catal. 2018, 8, 4473-4482; (m) Yu, H.; Li, Z.; Bolm, C. Nondirected Copper-Catalyzed Sulfoxidations of Benzylic C–H Bonds. Org. Lett. 2018, 20, 2076-2079; (n) Sekar, G.; DattaGupta, A.; Singh, V. K. Asymmetric Kharasch Reaction: Catalytic Enantioselective Allylic Oxidation of Olefins Using Chiral Pyridine Bis(Diphenyloxazoline)−Copper Complexes and TertButyl Perbenzoate. J. Org. Chem. 1998, 63, 2961-2967; (o) Li, Z.; Cao, L.; Li, C.-J. Fecl2-Catalyzed Selective CC Bond Formation by
Oxidative Activation of a Benzylic CH Bond. Angew. Chem. Int. Ed. 2007, 46, 6505-6507; (p) Pan, S.; Liu, J.; Li, H.; Wang, Z.; Guo, X.; Li, Z. Iron-Catalyzed N-Alkylation of Azoles Via Oxidation of C−H Bond Adjacent to an Oxygen Atom. Org. Lett. 2010, 12, 1932-1935; (q) Guo, S.; Wang, Q.; Jiang, Y.; Yu, J.-T. Tert-Butyl PeroxybenzoatePromoted Α-Methylation of 1,3-Dicarbonyl Compounds. J. Org. Chem. 2014, 79, 11285-11289; (r) Jian, W.; Ge, L.; Jiao, Y.; Qian, B.; Bao, H. Iron-Catalyzed Decarboxylative Alkyl Etherification of Vinylarenes with Aliphatic Acids as the Alkyl Source. Angew. Chem. Int. Ed. 2017, 56, 3650-3654; (s) Zhu, N.; Zhao, J.; Bao, H. Iron Catalyzed Methylation and Ethylation of Vinyl Arenes. Chem. Sci. 2017, 8, 2081-2085; (t) Xiong, H.; Ramkumar, N.; Chiou, M.-F.; Jian, W.; Li, Y.; Su, J.-H.; Zhang, X.; Bao, H. Iron-Catalyzed Carboazidation of Alkenes and Alkynes. Nat. Commun. 2019, 10, 122; (u) Tran, B. L.; Driess, M.; Hartwig, J. F. Copper-Catalyzed Oxidative Dehydrogenative Carboxylation of Unactivated Alkanes to Allylic Esters Via Alkenes. J. Am. Chem. Soc. 2014, 136, 17292-17301; (v) Tran, B. L.; Li, B.; Driess, M.; Hartwig, J. F. Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes. J. Am. Chem. Soc. 2014, 136, 2555-2563; (w) Bunescu, A.; Wang, Q.; Zhu, J. Synthesis of Functionalized Epoxides by Copper-Catalyzed Alkylative Epoxidation of Allylic Alcohols with Alkyl Nitriles. Org. Lett. 2015, 17, 1890-1893; (x) Tang, S.; Wang, P.; Li, H.; Lei, A. Multimetallic Catalysed Radical Oxidative C(Sp3)–H/C(Sp)–H Cross-Coupling between Unactivated Alkanes and Terminal Alkynes. Nat. Commun. 2016, 7, 11676. (9) (a) Gamez, P.; Arends, I. W. C. E.; Sheldon, R. A.; Reedijk, J. Room Temperature Aerobic Copper–Catalysed Selective Oxidation of Primary Alcohols to Aldehydes. Adv. Synth. Catal. 2004, 346, 805811; (b) Figiel, P. J.; Leskelä, M.; Repo, T. Tempo-Copper(II) Diimine-Catalysed Oxidation of Benzylic Alcohols in Aqueous Media. Adv. Synth. Catal. 2007, 349, 1173-1179; (c) Ryland, B. L.; Stahl, S. S. Practical Aerobic Oxidations of Alcohols and Amines with Homogeneous Copper/Tempo and Related Catalyst Systems. Angew. Chem. Int. Ed. 2014, 53, 8824-8838. (10) (a) Wiebe, H. A.; Heicklen, J. Photolysis of Methyl Nitrite. J. Am. Chem. Soc. 1973, 95, 1-7; (b) Banks, J. T.; Scaiano, J. C. The NeophylLike Rearrangement of Alkoxyl Radicals Revisited: Laser Flash and Laser Drop Photolysis Studies of 1,1-Diphenylethoxyl Radicals. J. Phys. Chem. 1995, 99, 3527-3531. (11) (a) Baroudi, A.; Mauldin, J.; Alabugin, I. V. Conformationally Gated Fragmentations and Rearrangements Promoted by Interception of the Bergman Cyclization through Intramolecular HAbstraction: A Possible Mechanism of Auto-Resistance to Natural Enediyne Antibiotics? J. Am. Chem. Soc. 2010, 132, 967-979; (b) Harris, T.; Gomes, G. d. P.; Clark, R. J.; Alabugin, I. V. Domino Fragmentations in Traceless Directing Groups of Radical Cascades: Evidence for the Formation of Alkoxy Radicals Via C–O Scission. J. Org. Chem. 2016, 81, 6007-6017.
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First acyl-cyanation of alkenes Copper catalysis Aromatic and aliphatic aldehydes Theoretical studies
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