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[4+2] Cycloaddition of vinylphosphine oxides to #-oxy-o-xylylene as a route to phosphorylated naphthyl and biaryl scaffolds Slawomir Frynas, El#bieta #astawiecka, Anna E. Koziol, Anna Flis, and K. Michal Pietrusiewicz J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02659 • Publication Date (Web): 11 Jan 2019 Downloaded from http://pubs.acs.org on January 11, 2019

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The Journal of Organic Chemistry

[4+2] Cycloaddition of vinylphosphine oxides to α-oxy-o-xylylene as a route to phosphorylated naphthyl and biaryl scaffolds Sławomir Frynas,† Elżbieta Łastawiecka,† Anna E. Kozioł,‡ Anna Flis,† K. Michał Pietrusiewicz*†

†Department

of Organic Chemistry, Faculty of Chemistry, Maria Curie-Skłodowska University, 33 Gliniana st., 20-614 Lublin, Poland e-mail: [email protected] ‡Department

of Crystallography, Faculty of Chemistry, Maria Curie-Skłodowska University, Pl. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland

OH

Ar

P(O)R1R2

OH

P(O)R1R2

P(O)R1R2

R1, R2 = alkyl, aryl R

R

α-Oxy-o-xylylene, a highly reactive diene readily accessible from benzocyclobutenol, undergoes Diels-Alder reaction with vinylphosphine oxides yielding the corresponding 2phosphorylated 1-hydroxy-1,2,3,4-tetrahydronaphthalenes in excellent yields. Use of unsubstituted and trans-2-aryl-substituted vinylphosphine oxides leads to cycloadducts with complete regioselectivity and with cis:trans selectivity up to 19:1 in the most favorable case. In case of P-stereogenic trans-2-aryl-substituted vinylphosphine oxides a virtually complete chirality transfer from P to C can be achieved. Dehydration and aromatization of the obtained cycloadducts bearing the resolved P-stereogenic phosphinoyl groups can be carried out to afford the valuable P-stereogenic and axially chiral phosphorylated 1,2’-binaphthyl ring system.

Cases

of

restricted

rotation

around

Csp3-Csp2

single

bond

in

some

tetrahydronaphthalene cycloadducts have also been revealed.

Introduction

ACS Paragon Plus Environment

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Chiral organophosphorus compounds have been widely used as ligands in asymmetric catalytic transformations driven by the transition metal complexes which allow the synthesis of chiral products from racemic or non-chiral substrates.1 A lot of structurally diversified chiral mono- and diphosphines possessing chirality centers both at carbon (DIOP,2 CHIRAPHOS3) and at phosphorus atoms (DIPAMP,4 CAMP5) or possessing axial chirality (BINAP,6 MOP7, SYNPHOS8) have been developed and used as effective ligands in asymmetric catalysis. In most cases, chiral phosphine ligands possessed only one type of chirality usually associated with the presence of chirality center either at the carbon backbone or at the phosphorus atom. Phosphine ligands possessing both the axial chirality element in the carbon backbone and the chirality center at the phosphorus atom were first synthesized by Cereghetti and co-workers in 1996.9 Later, several structurally different phosphines of this type, e.g., P-stereogenic MOP10 and MOP analogues11, MAP12, BI-BOP13 and modified BIBOP14, BI-DIME15, BoQPhos,16 were synthesized as well. A typical way to synthesize phosphorus ligands containing both the chirality at P and the axial chirality in the binaphthyl system is to use a readily available optically pure 1,1’binaphthol as the starting material, which can be transformed into an enantiomerically pure phosphine through a set of nowadays classical organic transformations.9 In the process, the existing binaphthyl chirality is used to resolve the P-centre. In this paper, we would like to propose a different approach to synthesis of Pstereogenic binaphthyl monophosphines which is based on the Diels-Alder reaction between trans-2-naphthylvinylphosphine oxides with α-oxy-o-xylylene (1) in the key step (Scheme 1). In such a sequence of events, use of a P-resolved dienophile 2 would promptly lead to the formation of the tetrahydrobinaphthyl intermediate 3 already incorporating the resolved P-unit as well as a hydroxyl group facilitating its further conversion to the target phosphorylated binaphthyl 4. One of advantages of this approach is the possible modulation of the phosphorus dienophile by easy changing the substitution pattern at both the phosphorus atom and at the vinylic fragment. In addition, it offers access to the less common 1,2'-type binaphthyls and may use chirality of the P-center to resolve the axially chiral 1,2’-binaphthyl unit.


2

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Scheme 1. Proposed approach to synthesis of axially chiral P-stereogenic 1,2’-binaphthyl monophosphines through the Diels-Alder pathway.

OH

1

n-BuLi -78 oC - rt

+

THF

O R P* 2R1

OH O * P R1 R2

O * P R2 R1

dehydration and aromatization

*

*

3

R

3

R 3

4

3

R 2

R1, R2 = alkyl, aryl R3 = H, Me, -OiPr, CH2P(O)Ph2

Chemical literature provides many examples of the use of vinylphosphine oxides as dienophiles in [4+2] cycloaddition reactions with a variety of different dienes.17 Usually, a catalyst-free thermally promoted Diels-Alder reaction of vinylphosphine oxides leads to the formation of a mixture of isomers in which an exo adduct is the major component.17c-e On the other hand, the same reaction performed in the presence of Lewis acid leads to the predominant formation of the endo isomer.17c-e Asymmetric non-catalyzed Diels-Alder reactions of either enantiopure or racemic P-stereogenic organophosphorus dienophiles with variety of dienes which were studied to date typically required elevated reaction temperatures to achieve high conversions and showed low stereoselectivity with no apparent distinction between the exo and the endo approach.17c,e We have expected that in the proposed strategy an anionic activation of α-oxy-o-xylylene18 would allow for carrying the cycloaddition reactions at low temperature possibly enabling high stereoselectivity to be achieved. Since reactions of α-oxy-o-xylylene with vinyl phosphorus compounds have not been studied before,18 we decided to include in our study a short series of model 2-unsubstituted vinylphosphine derivatives to get some basic data on the dependence of the reaction stereocourse on the character of the P-substitution as well as on its dissymmetry. Results and discussion


3


Page 4 of 39

Benzocyclobutenol (5), a precursor of α-oxy-o-xylylene (1), was prepared in threesteps according to a slightly modified procedure described by Bubb and Sternhell.19a Vinyl organophosphorus compounds used in the present study were synthesized by known methods except for diethyl vinylphosphonate (6) which was commercially available. Diphenylvinylphosphine oxide (7) and diphenylvinylphosphine sulfide (8) were synthesized from diphenylvinyl phosphine20 by oxidation with H2O2 and S8, respectively. Racemic methylphenylvinylphosphine oxide (9),21 its optically pure (SP)-9 enantiomer17a,22 as well as racemic and optically pure tert-butylphenylvinyl phosphine oxide (10)23 were obtained using described procedures. Racemic o-anisylphenylvinylphosphine oxide 11 was prepared from secondary o-anisylphenylphosphine oxide (13) and vinyl bromide in the presence of palladium catalyst (Scheme 2). Scheme 2. Synthesis of racemic o-anisylphenylvinylphosphine oxide (11)

O P oAn Ph H 13

Pd(PPh3)4 (8 mol%) vinyl bromide (14 equiv.) toluene, 60 oC, 48 h 53%

O P oAn Ph 11

1-Naphthylphenylvinyl phosphine oxide (12) was prepared according to a two-step protocol starting from secondary 1-naphthylphenylphosphine oxide (14) (Scheme 3).23 Scheme 3. Synthesis of racemic 1-naphthylphenylvinyl phosphine oxide (12)

O P H Ph 14

Ph

O S DBU

toluene, rt, 5 days 32%

O P Ph

S O

Ph

O P

toluene 120 oC, 24 h 56%

12

Aryl halides required for synthesis of 2-arylvinylphosphine oxides were commercially available except 1-(diphenylphosphinoylmethyl)-2-iodobenzene (17), which was obtained from 1-(chloromethyl)-2-iodobenzene (15) and ethyl diphenylphosphinite (16) (Scheme 4).


4

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Scheme 4. Synthesis of 1-(diphenylphosphinoylmethyl)-2-iodobenzene (16) via Arbuzov reaction. CH2Cl +

PPh2(OEt)

I 16

15

I

neat 105 oC, 1 h 85%

17

O P Ph Ph

The synthesis of 2-arylvinylphosphine oxides 18-24 was accomplished using the Heck reaction under the conditions described before24 (Table 1). Table 1. The Heck reaction of vinylphosphine oxides with aryl halides. ArXa (1 equiv.) Pd(OAc)2 (2% mol) PPh3 (10-20% mol), NEt3 (2 equiv.)

O P R' R 7-12

MeCN or DMF, 100-130 oC, 1-24 h 32%-95%b

O P Ph Ph

O P Ph Ph

a.

20 (86%) O P Me Ph

O P Ph t-Bu

22 (32%)

O P Ph Ph

O P Ph Ph P Ph O Ph

19 (90%)c

18 (95%)

Ar

O P R' R 18-24

23 (76%)

21 (86%) O P Me Ph

S-(-)-23 (74%)

O

O P Me Ph

24 (77%)

X = I or Br b. Isolated yields. c. Prolonged heating for 48 h was applied.

Generally, as shown in Table 1, the Heck coupling of aryl halides with vinylphosphine oxides proceeded efficiently affording the expected products in good yields except for compound 22 which was obtained in 32% yield. In one case, e.g., 19, heating of the reaction mixture for 48 h was necessary to obtain satisfactory conversion.


5


Page 6 of 39

With phosphorus dienophiles in hand, we subjected them to reactions with 5 according to procedure described by Choy and Yang.18a The results are presented in Tables 2 and 3. Table 2. The Diels-Alder reaction of benzocyclobutenol (5) with vinylphosphonate (6), vinyl phosphine oxide (7), and vinyl phosphine sulfide (8). OH OH + 5

X P R R

n-BuLi THF, -78 oC 1 h 0 oC 1 h

6 R = OEt, X = O 7 R = Ph, X = O 8 R = Ph, X = S

Entry

Substrate

OH

X P R R

cis

trans

25a R = OEt, X = O 26a R = Ph, X = O 27a R = Ph, X = S

Conv.a

Isolated yield

(%)

(%)

X P R R

25b R = OEt, X = O 26b R = Ph, X = O 27b R = Ph, X = S

Product ratioa 25a-27a

24b-27b

1

6

95

87

25a (42%)

25b (58%)

2

7

97

87

26a (59%)

26b (41%)

3

8

88

67

27a (10%)

27b (90%)

a Determined

by 31P NMR analysis of the crude reaction mixture.

All tested dienophiles exhibited high reactivity towards benzocyclobutenol (5) but stereoselectivity of the cycloaddition was strongly dependent on the structure of the dienophile. Treatment of 5 with phosphonate 6 afforded a mixture of two products isolated in 87% yield as a partially separated mixture of isomers with predominance of the trans isomer (cis:trans ratio 3:2). Under the same reaction condition diphenylvinylphosphine oxide (7) gave the two isomeric cycloadducts with the predominant formation of the cis isomer (cis:trans ratio 2:3) isolated in 87% yield. Even more decided bias for the formation of the trans isomer was observed in the case of phosphine sulfide 8, which yielded the cycloadducts in 67% isolated yield with a cis:trans ratio of 1:13. The configurations of the formed trans and cis cycloadducts have been assigned on the basis of 1H NMR signal of the carbinol proton in the two isomers. It could have been expected, that the vicinal coupling constants of the carbinol proton in the trans isomer would be larger than in its cis analog.25 The signal of the carbinol proton for the cis isomers was observed as a doublet of doublets with JH-H = 0 - 1.5 Hz and JP-H up to 7 Hz. The signal of the same proton for the trans isomers was observed as a triplet or as doublet of doublets with JH-H up to 4.3 Hz and JP-H up to 10.7 Hz. The correctness of these assignments was further


6

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corroborated by NOE experiments (Figure 1). The relative configurations of all cycloadducts obtained in the course of this study were assigned by the same token. Figure 1. NOE data for products 25-27. OH 1 X H P R R H2

OH 1 X H P R R H2

NOE

NOE

trans 25b R = OEt, X = O trans 26b R = Ph, X = O trans 27b R = Ph, X = S

cis 25a R = OEt, X = O 2.47 % cis 26a R = Ph, X = O 8.47 %

0.8 % 0% 0%

Next, in order to study influence of dissymmetry at phosphorus on stereochemistry of the cycloaddition, vinylphosphine oxides 9-12 possessing chirality center at phosphorus were submitted to reaction with 5 (Table 3). Table 3. The Diels-Alder reaction of benzocyclobutenol 5 with P-stereogenic vinylphosphine oxides. OH O P R Ph OH

O P R Ph

+

n-BuLi THF, -78 oC, 1 h

1 2 3

Substrate rac-9 (-)-9 rac-10

OH O P R Ph

OH O P R Ph

0 oC, 1 h

29b-31b cis 28 a cis 29 a,b cis 30 a,b cis 31 a,b

Entry

28c-31c

28a-31a

9 R = Me 10 R = t-Bu 11 R = o-An 12 R = 1-Naphthyl

5

OH O P R Ph

29d-31d

R = Me R = t-Bu R = o-An R = 1-Naphthyl

trans 28 c trans 28 c,d trans 30 c,d trans 31 c,d

R = Me R = t-Bu R = o-An R = 1-Naphthyl

Conv. a

Yieldb

(%)

(%)

cis 28a,b-31a,b

trans 28c,d-31c,d

99

72

28a:28b

28c:28d

(90%:0%)

(10%:0%)

28a:28b

28c:28d

(90%:0%)

(10%:0%)

29a:29b

29c:29d

(17%:1%)

(75%:7%)

99 98

82 66

Product ratiosa


7


4

(-)-10

5

rac-11

6

rac-12

a Determined

98 66 95

75 52 72

Page 8 of 39

29a:29b

29c:29d

(20%:1%)

(72%:7%)

30a:30b

30c:30d

(19%:8%)

(52%:21%)

31a:31b

31c:31d

(50%:12%)

(29%:9%)

by 31P NMR analysis of the crude reaction mixture. b Yields obtained after purification.

Again, the selectivity of the reaction was strongly influenced by the structure of the starting dienophile. Thus, phosphine oxide 9 possessing methyl group at phosphorus formed only one pair of cis and trans isomers (cis:trans ratio 9:1). On the other hand, phosphine oxide 10 possessing bulky tert-butyl group yielded all four possible isomers with predominant formation of the trans isomers (cis:trans ratio 1:4). Similar selectivity was observed for phosphine oxide 11, except for the somewhat lowered cis:trans ratio (1:2.7). The cycloaddition of phosphine oxide 12 appeared to be the least selective yielding predominantly the cis isomers (cis:trans ratio 3:2). It can thus be concluded that vinylphosphine oxides possessing an alkyl group at phosphorus yield the corresponding cycloadducts with significantly higher stereoselectivity as compared to diarylvinylphosphine oxides. It should also be noticed that in the studied reactions the induction by the P-stereogenic center has reached an unprecedentedly high level in either P-endo or P-exo cycloaddition stereocourse leading to cis and trans products, respectively. The relative configuration of the main trans isomer 29c was additionally determined by an X-ray single-crystal analysis (cf. Supplementary Information) and unequivocally confirmed the original NMR assignments.

Finally, -substituted vinylphosphine oxides 18-24 were subjected to cycloaddition reactions with benzocyclobutenol (5) (Table 4).


8

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Table 4. The Diels-Alder reaction of -substituted vinylphosphine oxides with 5. OH O P R 2 R1

Ar

5

Entry

Substrate

Ar

Ar

n-BuLi, -78 oC, 1 h

18-24

32a-37a-cis,trans

0 oC, 1 h.

Conversion Cis,trans 32a-37a

18

32b-37b-trans, trans

Product ratioa

(%)a,b

1

OH O P R 2 R1

OH O P R 2 R1 +

OH O P Ph Ph

75 (54)

Trans, trans 32b-37b OH O P Ph Ph

7:93

32a

32b

OH OH O P Ph Ph

2

19

99(75)

10:90 33b

33a

OH O P Ph Ph

OH O P Ph Ph

3

20

55 (35)

40:60 34b

34a

OH O P Ph Ph

OH O P Ph Ph

4

21

99 (78)

5:95 O P Ph Ph

O P Ph Ph

35b

35a

5

22

O P Ph Ph

No reaction


9


Page 10 of 39

OH O P Ph Me

OH O P Ph Me

6

(S)-23

100 (70)

94:6 36b

36a

7

24

97 (79)

OH O P Me Ph O

OH O P Me Ph O

85:15

37a a Determined

37b

by 31P NMR analysis of the crude reaction mixture. b Isolated yields are placed in parentheses.

Results presented above allow to draw some correlations between the structure of the substrate and the stereochemistry of the studied Diels-Alder reactions. In most of the cases, substituted vinylphosphine oxides 18-24 readily underwent cycloaddition reaction with 5, except phosphine oxide 22 which was recovered unchanged from the reaction mixture. Furthermore, phosphine oxides possessing two phenyl groups at the phosphorus atom yielded trans isomers preferentially with a trans:cis ratio ranging from 19:1 to 3:2 and diminishing with the size of the 2-aryl group increased (entries 1-4, Table 4). On the other hand, phosphine oxides 23 and 24 possessing less bulky and more electron reach Ph,Me substitution at the phosphorus atom, afforded the cis isomer in very high predominance. The best selectivity was observed for optically pure (SP)-(-)-23 (trans:cis ratio 1:16, entry 6, Table 4). Importantly, like in the case of methylphenylvinylphosphine oxide (9), phosphine oxides 23 and 24 gave only single isomers of cis and trans cycloadducts confirming again the possibility of reaching practically 100% induction level by the stereogenic phosphorus center. It was also interesting to find that some of the obtained cycloadducts exhibited partially hindered rotation around Csp3-Csp2 single bond at room temperature. This has been demonstrated for cycloadducts 33b and 35b which were isolated as single diastereoisomers and were analyzed by variable temperature 1H NMR. As shown in Figures 2, signals of H-2’ and H-3’ protons in 33b appeared as broad signals at 298 K but at 348 K and 248 K they were sharp and well resolved, what suggests signal coalescence close to room temperature.


10

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Figure 2. Selected region of 1H NMR spectra of 33b analyzed at: a) 328 K; b) 298 K; c) 248 K.

A similar situation was also observed for cycloadduct 35b (Figure 3). Signals of H-2, H-4a and one proton from the benzyl group were broad at room temperature but were well resolved at 348 K and at 248 K. Moreover, signals of C-2 and C-3 in 13C NMR spectrum of 35b were also observed as broad peaks of very low intensity (cf. Supplementary Information). These observations confirm again the presence of partially hindered rotation around Csp3Csp2 single bond in 35b at room temperature. Figure 3. Selected region of 1H NMR spectra of 35b analyzed at: a) 328 K; b) 298 K; c) 248 K.


11


Page 12 of 39

This type of Csp3-Csp2 single bond atropoisomerism has not been very common although it was previously observed in several structurally diversified compounds26 including carbinols26d and naphthylcarbinols.26e In the studied cycloadducts, it can be assumed that the observed partially restricted rotation is a consequence of steric interactions between a large diphenylphosphinoyl substituent and an aryl substituent placed in the neighboring position. Assuming that the signal of H-2’ proton in the cycloadduct 33b undergoes coalescence at 25 oC,

the exchange rate at this temperature could be approximated by the equation kc = πΔν/21/2

where Δν is the separation of the coalescing peaks in hertz.26a,b The rotational barrier (ΔG*) for 33b calculated from the Eyring equation26a,b was found to be ca. 16.9 kcal/mol. Another interesting spectral feature has also been observed in the 1H NMR spectrum of cycloadduct 36a. For this compound, a signal of the P-methyl group appeared at 0.45 ppm and signal of benzylic H-3’ was found at 5.12 ppm. Typical chemical shift for P(O)-Me groups is about 1.6-2.2 ppm17a,27 and the chemical shift of benzylic protons is about 2.4-4.3 ppm.28 Such a strong shift observed for the P-methyl signal in 36a suggested that the Pmethyl group is strongly shielded by the 2-methylnaphthyl group. In turn, downfield shift of benzylic H-2’ proton suggested that it was situated in a syn-axial position to the hydroxy group which enabled strong deshielding of this proton by hydroxyl oxygen. These


12

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assumptions allowed for the configurational and conformational assignment of 36a as presented in Figure 4. Figure 4. Configurational and conformational assignment for 36a 5.12 ppm

H Me

OH O P Me 0.45 ppm

36a

From the results of the studied cycloaddition reactions of 5 with vinylphosphine oxides some conclusions regarding their stereoselectivities can be drawn. In such reactions, unsubstituted vinylphosphine oxides usually form a mixture of cis and trans cycloadducts with a bias at either side depending primarily on the substitution at P. Diaryl substitution at phosphorus favors formation of the trans product while mixed aryl,alkyl substitutions at P leads, in most cases, to the formation of the cis product. The same stereoselectivity pattern is observed also in cycloadditions of vinylphosphine oxides bearing terminal aryl substituents although now the analogous preference for the formation of either trans or cis products is by far more pronounced. It reaches up to 19:1 trans to cis selectivity on one hand (Table 4, entry 1) and up to 16:1 cis to trans selectivity on the other (Table 4, entry 6). In the latter case, the best results were obtained in reactions of 5 with 2-arylvinylphosphine oxides possessing the Ph,Me substituted phosphorus center preferring decidedly the P-endo approach (Scheme 5). Scheme 5. Stereochemistry of the formation of the cis,trans-cycloadducts


13


Page 14 of 39

R3 H OLi O

OH O P R1 R2 R3

1

P

R

R2

H

H

H

H

OH

P(O)R1R2

H

3

R

OH

H

23 R1 = Me, R2 = Ph, R3 = 2-methylnapthyl 24 R1 = Me, R2 = Ph, R3 = 2-isopropoxynaphthyl

H P(O)R1R2

3

HR

endo approach

cis, trans 36a cis, trans 37a

H

Considering that the conjugated olefins e.g., acrylates28 as well as vinyl sulfoxides29 and unsubstituted vinylphosphine oxides30 are inclined to react in an s-cis conformation, and that the favored conformation of methylphenylvinylphosphine oxide in the crystalline state is also s-cis,22 it can be assumed that terminally substituted dienophiles 23 and 24 adopt similar s-cis conformation in the transition state. Facial selectivity in these reactions could be then effectively controlled by the different size of substituents at the phosphorus stereocenter. It seems also possible that the observed P-endo approach of the two reactants might be additionally aided by possible favorable interactions between lithium cation and the phosphoryl oxygen (cf. Table 1, entries 2 and 3). In turn, increased bulkiness of the phosphinoyl group in 2-arylvinylphosphine oxides bearing two phenyl groups at P forces them to follow the P-exo approach in their reactions with 5 (Scheme 6). In this approach a possible attractive - interactions between the diene and the now endo 2-aryl group may also come into play. Scheme 6. Stereochemistry of the formation of the trans,trans-cycloadducts OLi

R3

OH R2 P R1 O

19 R1 = R2 = Ph, R3 = Aryl 21 R1 = R2 = Ph, R3 = Aryl

O P R1 R2 R3

H H H

OH P(O)R1R2

R3 H H tr ans, tr ans tr ans, tr ans

33b 35b

exo approach


14

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To verify the possibility of converting the obtained cycloadducts into axially chiral 3,phosphinoyl-1,2'-binaphthyls a direct aromatization of their tetrahydronaphthalene core was attempted. Unexpectedly, treatment of a mixture of (SP)-36a:36b (cis:trans 16:1) with DDQ31 at 100-130 oC or with Pd/C32 at 170-200 oC afforded only complex mixtures of 6-8 products. Hence, the direct approach was changed to a two-step aromatization process entailing dehydration of the cycloadducts (SP)-36a,b in the first step followed by the oxidation of the resulting dihydronaphthalene intermediate in the second. It was found that dehydration of 36a,b could be efficiently conducted under three different reaction conditions using either PBr3,33 or mesyl chloride/NEt3,34 or NaI/CeCl3*7H2O/95 oC 35 (Table 5). Table 5. Dehydration of the cycloadducts (SP)-36a,b OH O *P Ph Me

O * P Ph Me condition a,b,c

36a:36b (cis:trans 16:1)

No

38a:38b (3.3:1)

Conditions

Yield (%)a

1

PBr3 (10 equiv.), CHCl3, rt, 72 h

82 (65)b

2

Mesyl chloride (3.5 equiv.), Et3N (10 equiv.),THF/0 C 1.5 h

78 (67)b

3

NaI (2.4 equiv.)/CeCl3*7H2O (1.5 equiv.), acetonitrile, 95 C,

100 (91)b

48 h a Determined

by 31P NMR analysis of the crude reaction mixture. b Isolated yield in parenthesis.

In each case, formation of the corresponding dehydration products proceeded well although the NaI/CeCl3 system showed markedly better performance. Interestingly, the formation of a 3.3:1 mixture of the diastereoisomeric products 38a and 38b has been observed in each case. Assuming that there was no epimerization at the C-2’carbon atom, the same product ratio observed under three different reaction conditions must have apparently been a consequence of the effectively slowed down rotation around Csp3-Csp2 single bond resulting in the formation of 38a and 38b as the two axial epimers. All our attempts to separate 38a and


15


Page 16 of 39

38b failed. In this situation, we decided to check the aromatization of the 38a,b using the racemic mixture obtained from rac-36a,b in a separate run (Scheme 7). Scheme 7. Aromatization of 38a,b O P Me Ph

O P Me Ph

DDQ 3 equiv.

O P Me Ph

+

dioxane, 120 oC, 48 h 92%

1.2 : 1 38a:38b (3.3:1)

39a (SaSP,RaRP)

39b (RaSP,SaRP)

As shown in Scheme 7, heating racemic 38a,b with 3 equiv. of DDQ at 120 ºC for 2 days led to the formation of a mixture of atropoisomeric phosphine oxides 39a and 39b in a 1.2:1 ratio in 92% yield. The mixture was separated by crystallization from acetone and the molecular structure of the minor atropoisomer 39b has been determined by an X-ray singlecrystal structure analysis (cf. Supplementary Information), allowing the assignment of relative configurations to the two isomers. In summary, it has been demonstrated that the selectivity of cycloaddition reaction between vinylphosphine oxides and 5 strongly depends on the substitution pattern at the phosphorus atom and at the vinyl terminus. The structural assignment of the cycloadducts was based on detailed NMR analysis and X-ray structural analysis. All studied cycloadditions proceeded with high conversion and provided the expected products in good to excellent yields. The best results in terms of conversion (100%) and selectivity (94:6 cis,trans:trans,trans)

were

obtained

with

vinylphosphine

oxides

derived

from

methylphenylvinylphosphine oxide and possessing a bulky 2-aryl substituent at the vinyl group.

The

cycloaddition

reactions

utilizing

non-racemic

P-stereogenic

methylphenylvinylphosphine oxides led to cycloadducts with virtually 100% asymmetric induction in both the endo and the exo approach. The studied cycloadditions open up a new route to the biaryl and, particularly, 1,2’-binaphthyl systems bearing phosphorus functionality which may serve as useful precursors of new phosphorus ligands containing axial and Pcentered chirality elements. This part of our research is currently underway in our laboratory.


16

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Experimental Section

All reagents were obtained from commercial suppliers. Tetrahydrofuran, ether, benzene, and toluene were dried by refluxing with sodium and used after distillation under argon, hexane and acetone were distilled from molecular sieves (5 A) under argon. Methylene chloride and chloroform were distilled from P2O5 under argon. Compounds purification was performed using column chromatography. All reactions were carried out under argon atmosphere. NMR spectra were recorded with 300 and 500 MHz spectrometers in CDCl3 as a solvent at room temperature unless otherwise noted. Chemical shifts (δ) are given in ppm relative to tetramethylsilane (1H), external 85% H3PO4 (31P), or residual CHCl3 (13C) as a reference. All

31P

NMR and

13C

NMR spectra were recorded with the use of broadband

proton decoupling. The following abbreviations are used in reporting NMR data: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad). Coupling constants (J) are in Hz. High‐resolution mass spectrometry analyses were obtained using LCMS IT-TOF spectrometer. Melting points were determined in a capillary tube apparatus. X-ray crystallography: The diffraction data for 29c and 39b were collected at 120 K with the Oxford Diffraction SuperNova diffractometer using graphite monochromated CuK radiation. Crystal structure was solved by direct methods using the SHELXS-97 program and refined by full-matrix least squares method on F2 using the SHELXL-97 program.36 All nonhydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms were positioned geometrically and allowed to ride on their parent atoms. The experimental details and final atomic parameters for 29c and 39b have been deposited with the Cambridge Crystallographic Data Centre as supplementary material (CCDC ID: 1851533 and 1851534). Copies of the data can be obtained free of charge on request by e-mailing [email protected] or via www.ccdc.cam.ac.uk/data_request/cif. o-Anisylphenylvinylphosphine oxide (11). A

mixture

of

o-anisylphenylphosphine

oxide

(0.1

g,

0.431

mmol),

tetrakis-

(triphenylphosphine)palladium(0) (0.04 g, 0.0345 mmol, 8% mol.), vinyl bromide (0.42 mL, 6 mmol, 14 equiv.), and triethylamine (0.06 mL, 4.3 mmol) in 2 mL of toluene was heated for 48 h at 60 oC. Then, solvent was evaporated under reduced pressure and the residue was


17


Page 18 of 39

dissolved in 15 mL of dichloromethane. Organic phase was washed with 1M HCl (10 mL), water (2*10 mL) and dried over MgSO4. The solid was filtered off and the filtrate was evaporated to dryness. The obtained residue was purified by column chromatography using chloroform:acetone (15:1) as eluent affording compound 11 (55 mg, 53 % yield) as a white solid,

mp 107‒108 C. 31P

NMR (CDCl3, 202.5 MHz): δ 20.95 ppm. 1H NMR (CDCl3, 500 MHz): δ 8.04 (ddd, J =

13.1 Hz, and 7.6 Hz and 1.7 Hz, 1H), 7.67 (ddd, J = 12.8 Hz, and 8.2 Hz and 0.8 Hz, 2H), 7.56‒7.53 (m, 1H), 7.50-7.46 (m, 1H), 7.43‒7.40 (m, 2H), 7.15 (td, J = 7.4 Hz and 7.4 Hz and 0.9 Hz, 1H), 6.95‒6.84 (m, 2H), 6.57‒6.48 (m, 1H), 6.36‒6.25 (m, 1H), 3.69 (s, 3H)

13C

NMR (CDCl3, 125.8 MHz): δ 161.1 (d, J = 5.0 Hz), 134.2, 134.1, 134.1, 134.1, 134.0 (d, J = 106.3 Hz), 131.3 (J = 2.5 Hz), 130.9 (d, J = 99.0 Hz), 130.7, 130.6, 128.3, 128.2, 121.2 (d, J = 11.8 Hz), 120.0 (d, J = 101.3 Hz), 111.0 (d, J = 7.3 Hz), 55.3. MS (EI HR) for C15H15O2PNa [M + Na]+: calc. 281.0702, found 281.0703.

(rac)-1-Naphthylphenylvinylphosphine oxide (12) was prepared according to procedure described in the literature for synthesis of tert-butylphenylvinylphosphine oxide.23 A mixture of 2-(diphenylphosphinoyl)naphthalene (1.1 g, 4.4 mmol), phenylvinylsulfoxide (0.68 g, 4.4 mmol), and DBU (0.68 g, 4.4 mmol) was stirred under argon for 3 d. The mixture was washed with 5% HCl (2*20 mL), then once with water (15 mL), and dried over MgSO4. The solid was filtered off and the filtrate was evaporated to dryness. The obtained residue was purified using column chromatography using chloroform:acetone (10:1) as eluent affording crude adduct (1.2 g). The crude adduct (0.6 g, 1.48 mmol) was heated in toluene (3 mL) under argon at reflux for 24 h. Then, toluene was evaporated in vacuo and the residue was purified using flash chromatography with chloroform:methanol as eluent (20:1). Crystallization of the product from hexane-toluene mixture (1:1) yielded phosphine oxide 12 (0.23 g, 0.83 mmol, 56%) as white crystals, mp 176‒177 oC. 31P

NMR (CDCl3, 121.5 MHz): δ 25.84 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.35 (d, J = 8

Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.83-7.36 (m, 10H), 6.85-6.65 (m, 1H), 6.36-6.18 (m, 2H). 13C

NMR (CDCl3, 75.5 MHz): δ 135.0, 134.0, 133.9, 133.7, 133.4, 133.4, 133.4, 133.2, 133.1,

133.0, 132.3, 132.3, 132.0 (d, J = 2.8 Hz), 131.3 (d, J = 10.1 Hz, 2C), 129.6, 129.0, 129.0,


18

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128.8 (d, J = 12.2 Hz, 2C), 127.8, 127.6, 127.0, 126.9, 126.5, 124.6, 124.4. Anal. Calcd. for C18H15OP: C, 77.69; H 5.43. Found: C, 77.92; H 5.48. 1-(Diphenylphosphinoylmethyl)-2-iodobenzene (17). 1-Chloromethyl-2-iodobenzene (4.01 g, 0.016 mol) was placed in a 250 mL flask equipped with dropping funnel, reflux condenser, thermometer, argon inlet, and magnetic stirrer. A small amount of ethyl diphenylphosphinite was added at 105 C. The rest of ethyl diphenylphosphinite (3.60 g, 0.016 mol) was then added at a rate sufficient to maintain the reaction temperature at 105-110 oC. After addition of the whole the reaction was stirred at 105 C for 1 h. The crude product was crystallized from acetone:diethyl ether 1:1 to afford 5.57 g (0.0137 mol, 85%) of 17 as white crystals, mp 97‒98 oC. 31P

NMR (CDCl3, 121.5 MHz): δ 29.87. 1H NMR (CDCl3, 300 MHz): δ 7.85‒7.4 (m, 12 H),

7.26 (dt, J = 0.7 and 7.6 Hz, 1H), 6.87 (tt, J = 1.7 Hz and 7.6 Hz, 1H), 3.9 (d, J = 13.9 Hz, 2H). 13C NMR (CDCl3, 75.5 MHz): δ 139.3 (d, J = 2.1 Hz), 134.9 (d, J = 7.2 Hz), 131.8 (d, J = 2.7 Hz, 2C), 131.8 (d, J = 99 Hz, 2C), 131.1 (d, J = 9.3 Hz, 4C), 130.8 (d, J = 4.4 Hz), 128.4 (d, J = 2.7 Hz), 128.3 (d, J = 11.8 Hz, 4C), 128.1 (d, J = 2.5 Hz), 102.3 (d, J = 7.8 Hz), 42.2 (d, J = 65.7 Hz). Anal. Calcd. for C19H16IOP: C, 54.57; H, 3.86. Found: C, 54.55; H, 3.71. 1-[(E)-2-(Diphenylphosphinoyl)vinyl]-2-methylnaphthalene (20). Diphenylvinylphosphine oxide (0.668 g, 2.93 mmol), (0.71 g, 3.2 mmol) 1-bromo-2-methylnaphthalene, palladium acetate (0.016 g, 2% mol), triphenylphosphine (0.126 g, 0.48 mmol), and triethylamine (1 g, 0.01 mol) in 10 mL DMF were heated under argon at 120 oC for 24 hour. Then, the reaction mixture was cooled to rt, methylene chloride (100 mL) was added and the organic phase was washed tree times with 5% HCl (3*10 mL), then once with water and dried over anhydrous MgSO4. The crude product was isolated by column chromatography on silicagel using chloroform:acetone 3:1 as eluent, and was crystallized from hexane:toluene (1:1) to afford 0.925 g (86%) of 20 as white crystals. 20: white crystals, mp 154‒155 oC. 31P NMR (CDCl3, 121.5 MHz): δ 23.89. 1H NMR (CDCl3, 300 MHz): δ 7.92‒7.85 (m, 2H), 7.79-7.67 (m, 5H), 7.61 (d, J = 8.4 Hz, 1H), 7.45-7.28 (m, 8H), 7.21 (d, J = 7.4 Hz, 1H), 6.60 (dd, J = 17.2 Hz and 24.5 Hz, 1H), 2.38 (s, 3H, CH3). 13C NMR (CDCl3, 75.5 MHz): δ 146.0 (d, J = 3.2 Hz), 133.7, 133.5 (bs), 132.3, 132.1 (d, J = 11.3 Hz), 132.0 (d, J = 2.8 Hz, 2C), 131.8 (d, J = 76.5 Hz, 2C), 131.4 (d, J = 10 Hz, 4C), 128.9, 128.8 (d, J = 12.1 Hz, 4C), 128.6, 128.5, 128.4, 127.3, 125.9 (d, J = 105 Hz), 124.5, 21.0. Anal. calcd. for C25H21OP: C, 81.50; H, 5.75. Found: C, 81.34; H, 5.74. ACS Paragon Plus Environment

19


Page 20 of 39

1-(Diphenylphosphinoylmethyl)-2-[(E)-2-(diphenylphosphinoyl)vinyl]benzene

(21).

Diphenylvinylphosphine oxide (0.22 g, 0.96 mmol), iodide 17 (0.4 g, 0.96 mmol), palladium acetate (0.0043 g, 2% mol), triethylamine (0.16 g, 1.6 mol) in 10 mL of acetonitryl was heated under argon at 100 oC for 24 hour. Then, the reaction mixture was cooled to rt, methylene chloride (50 mL) was added and the organic phase was washed three times with 5% HCl (3*10 mL), then washed once with water (10 mL) and dried over anhydrous MgSO4. The crude product was separated by SiO2 column chromatography (chloroform:acetone 5:1) and crystallized from toluene to afford 0.43 g (0.83 mmol, 86%) of 21 as white crystals, 21: white crystals, mp 175‒176 oC.

31P

NMR (CDCl3, 121.5 MHz): δ 29.14 ppm and 24.43

ppm. 1H NMR (CDCl3, 300 MHz): δ 7.76‒7.1 (m, 4H), 7.62‒7.56 (m, 4H), 7.52‒7.27 (m, 15 H), 7.21‒7.18 (m, 2H), 6.69 (dd, J = 18.2 Hz and 21.8 Hz, 1H), 3.69 (d, J = 14.6 Hz).

13C

NMR (CDCl3, 75.5 MHz): δ 144.6 (d, J = 3.5 Hz), 134.9 (dd, J = 5.5 Hz and 18 Hz), 132.6 (d, J = 105.5 Hz, 2C), 131.8 (d, J = 3.1 Hz, 2C), 131.8 (d, J = 88 Hz, 2C), 131.7 (d, J = 3.1 Hz, 2C), 131.6 (d, J = 4 Hz), 131.4 (d, J = 9.9 Hz, 4C), 131.1 (d, J = 9.9 Hz, 4C), 130.4 (d, J = 8.1 Hz), 129.5 (d, J = 2.6 Hz), 128.5 (d, J = 11.8 Hz, 4C), 128.4 (d, J = 11.8 Hz, 4C), 127.3 (d, J = 2.8 Hz), 126.7, 121.6 (d, J = 103.2 Hz), 34.5 (d, J = 65,4 Hz). Anal. Calcd. for C33H28O2P2: C, 76.44; H, 5.44. Found C, 76.61; H, 5.46.

1-[(E)-2-(t-Butylphenylphosphinoyl)vinyl]naphthalene

(22).

A

mixture

of

t-

butylphenylvinylphosphine oxide (0.667 g, 3.2 mmol), 1-bromonaphthalene (0.667 g, 3.2 mmol), palladium acetate (0.016 g, 2% mol), triphenylphosphine (0.126 g, 0.48 mmol), and triethylamine (1 g, 0.01 mol) in 10 mL of DMF was heated under argon at 120 oC for 24 hour. Then, the reaction mixture was cooled to rt, methylene chloride (100 mL) was added and the organic phase was washed tree times with 5% HCl (3*10 mL), then with water (10 mL) and dried over anhydrous MgSO4. The crude product was separated by SiO2 column chromatography (chloroform:acetone 5:1), and crystallized from toluene to afford 0.36 g (0.95 mmol, 32%) of 22 as white crystals. 22: white crystals, mp 188‒189 oC.

31P

NMR (CDCl3, 121.5 MHz): δ 39.24 ppm. 1H NMR

(CDCl3, 300 MHz): δ 8.48 (t, J = 17.2 Hz, 1H), 8.23‒8.2 (m, 1H), 7.9‒7.83 (m, 4H), 7.75 (d, J = 7.2 Hz, 1H), 7.57‒7.47 (m, 6H), 7.01 (dd, J = 17 Hz and 26.2 Hz, 1H), 1.23 (d, J = 15.1 Hz, 9H). 13C NMR (CDCl3, 75.5 MHz): δ 146.7, 134.0 (d, J =10.6 Hz), 139.9, 133.1 (d, J = 111 Hz), 132.3 (d, J = 7.9 Hz), 131.5, 131.1, 130.5, 129.0, 128.7 (d, J = 10.7 Hz), 127.2, 126.6,


20

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125.8, 125.0, 124.2, 119.1 (d, J = 91.8 Hz), 33.5 (d, J = 76.3 Hz), 24.8 (3C). Anal. Calcd. for C22H23OP: C, 79.02; H, 6.93. Found: C, 78.79; H, 6.89. (Sp)-(-)-1-[(E)-2-(methylphenylphosphinoyl)vinyl]-2-methylnaphthalene [(SP)-(-)-23)]. A mixture of (Sp)-(-)-methylphenylvinylphosphine oxide (0.89 g, 5.36 mmol), 1-bromo-2methylnaphthalene (1.54 g, 6.9 mmol), palladium acetate (0.025 g, 2% mol), triethylamine (1.6 g, 18 mmol), triphenylphosphine (0.23 g, 0.88 mmol) in 10 mL of DMF was heated under argon at 120 oC for 24 hour. Then, the reaction mixture was cooled to rt, methylene chloride (100 mL) was added and the organic phase was washed tree times with 5% HCl (3*10 mL), then with water (10 mL), and dried over anhydrous MgSO4.The crude product was separated by SiO2 column chromatography (chloroform:acetone 5:1), and crystallized from toluene to afford 1.23 g (4 mmol, 74%) (Sp)-(-)-23 as white crystals. (Sp)-(-)-23: white crystals, mp 144-145 oC, []D20 ‒12 (c 1.6, CHCl3).

31P

NMR (CDCl3,

121,5 MHz): δ 26.46 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.99‒7.96 (m, 1 H), 7.91-7.78 (m, 4H), 7.72 (d, J = 8.4 Hz, 1H), 7.58‒7.51(m, 3 H), 7.47‒7.4 (m, 2H), 7.32 (d, J = 8.4 Hz, 1H), 6.44 (dd, J = 17.7 Hz and 25.5 Hz, 1H), 2.47 (s, 3H, CH3), 1.95 (d, J = 13.2 Hz, 3H).

13C

NMR (CDCl3, 75.5 MHz): δ 144.4 (d, J = 2.7 Hz), 133.9 (d, J = 102.4 Hz), 133.4 (bs), 132.2, 132.1 (d, J = 17 Hz), 131.9 (d, J = 2.8 Hz), 131.3 (bs), 130.2 (d, J = 9.7 Hz, 2C), 130.1, 129.0, 128.9 (d, J =11.9 Hz, 2C), 128.8, 128.4, 128.4, 125.9 (d, J = 100.8 Hz), 124.5, 20.9 (CH3), 17.2 (d, J = 74.5 Hz). Anal. Calcd. for C20H19OP: C, 78.41; H, 6.25. Found: C, 78.10; H 6.34. The same reaction with rac-methylphenylvinylphosphine oxide as a substrate yielded 1.26 g (4.1 mmol, 76%) of rac-23 as white crystals; mp 140-143 oC. 1-[(E)-2-(methylphenylphosphinoyl)vinyl]-2-i-propoxynaphthalene (24). A mixture of rac-methylphenylvinylphosphine

oxide

(0.30

g,

1.78

mmol),

1-bromo-2-

isopropoxynaphthalene (0.44 g 1.95 mmol), palladium acetate (0.01 g, 2.4% mol), triethylamine (0.60 mL, 4.9 mmol), and triphenylphosphine (0.047 g, 0.179 mmol) in 4 mL of DMF was heated under argon at 120 oC for 24 hour. Then, the reaction mixture was cooled to rt, methylene chloride (50 mL) was added and the organic phase was washed tree times with 5% HCl (3*10 mL) and water (10 mL), and dried over anhydrous MgSO4. The crude product was separated by SiO2 column chromatography (chloroform:acetone 3:1), and crystallized from toluene to afford 0.5 g (1.4 mmol, 77%) of 24 as white crystals. 24: white crystals, mp 119‒120 oC.

31P


(CDCl3, 300 MHz): δ 8.12 (d, J = 8.6 Hz, 1H), 7.95 (dd, J = 17.7 Hz and 21.7 Hz, 1H), 7.9-


21


Page 22 of 39

7.83 (m, 2H), 7.79‒7.51 (m, 2H), 7.54‒7.44 (m, 4H), 7.39‒7.33 (m, 1H), 7.24 (d, J = 9.4 Hz, 1H), 6.95 (dd, J = 17.7 Hz and 26.2 Hz, 1H), 4.69 (septet, J = 6.1 Hz, 1H), 1.91 (d, J = 13.1 Hz, 3H), 1.39 (d, J = 6 Hz, 3H), 1.30 (d, J = 6 Hz, 3H).

13C

NMR (CDCl3, 75.5 MHz): δ

154.3 (d, J = 1.5 Hz), 139.5 (d, J = 3.9 Hz), 134.3 (d, J = 101.7 Hz), 133.7, 131.5 (d, J = 2.7 Hz), 130.8, 130.2 (d, J = 9.8 Hz, 2C), 129.0, 128.6, 128.4 (d, J = 12 Hz, 2C), 127.1, 127.0 (d, J = 98.5 Hz), 124.0, 123.4, 119.4 (d, J = 17.1 Hz), 116.0, 72.0, 22.5, 22.4, 17.1 (d, J = 74.5 Hz). Anal. Calcd. for C22H23O2P: C, 75.41; H, 6.62. Found C, 75.43; H, 6.69.

General Procedure for Diels-Alder reaction of α-oxy-o-xylylene and phosphorus dienophiles To a cooled (-78 oC) solution of benzocyclobutenol (1-5 equiv.) in THF was added dropwise 1.6 M n-BuLi (1.1 equiv.). After stirring at -78oC for 30 min., phosphorus dienophile (1 equiv.) in THF was added dropwise and the resulting mixture was stirred at -78 oC for 1 h, then warmed and stirred at 0 oC for 1 h. The resulting mixture was concentrated in vacuo. To the residue methylene chloride and saturated NH4Cl solution were added. The mixture was washed with water and the organic fraction was dried over MgSO4. The solution was filtered and concentrated under reduced pressure. The residue was purified using column chromatography. The cis and trans stereochemistry of the cycloadducts was assigned by analysis of the coupling constants of carbinol protons and NOE spectra. (1-Hydroxy-1,2,3,4-tetrahydronaphth-2-yl)phosphonic

acid

diethyl

ester

(25a,b).

Prepared according to the general procedure from 0.75 g (6.25 mmol) of benzocyclobutenol, 4.5 mL of 1.6 M n‒BuLi (1.1 equiv), 0.252 g (1.537 mmol) of vinylphosphonic acid diethyl ester 9 in 100 mL of THF. The 1H NMR and 31P NMR of the crude reaction mixture indicated 95% conversion to the desired product formed as a 3:2 (trans:cis) mixture of diastereoisomers. Silica gel chromatography (10:1, chloroform:acetone) of the mixture led to isolation of 120 mg (0.43 mmol, 35%) of pure trans isomer as a white solid, 56 mg (0.2 mmol, 17%) of pure cis isomer as a white solid; and 120 mg (0.423 mmol, 35%) of a mixture of the two isomers. Cis-25a: white solid, mp 85‒86 oC. 31P NMR (CDCl3, 121.5 MHz): δ 31.37 ppm 1H NMR (CDCl3, 300 MHz): δ 7.37‒7.11 (m, 4H), 5.05 (bdd, JHH = 1.5 Hz, JPH = 7 Hz, 1H), 4.24‒4.12 (m, 4H), 3.02‒2.95 (m, 1H), 2.85‒2.74 (m, 1H), 2.35‒2.17 (m, 2H), 2.11‒2.01 (m, 1H), 1.36 (dt, J = 7.2 Hz and 7.2 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 137.3 (d, J = 14.4 Hz), 136.1


22

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(d, J = 0.7 Hz), 130.3 (d, J = 1.5 Hz), 129.4, 128.6, 126.7, 66.6 (d, J = 5.5 Hz), 62.7 (d, J = 6.7 Hz), 62.3 (d, J = 6.8 Hz), 39.4 (d, J = 143.5 Hz), 29.1 (d, J = 15,5 Hz), 17.9 (d, J = 3 Hz), 16.9 (d, J = 5.6 Hz, 2C). Anal. Calcd. for C14H21O4P: C, 59.15; H, 7.45. Found: C, 58.88; H, 7.56. Trans-25b: white solid, mp 68-69 oC. 31P NMR (CDCl3, 121.5 MHz): δ 31.75 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.56 (d, 1H, J = 7.7 Hz), 7.17–7.08 (m, 2H), 6.99 (d, 1H, J = 7.5 Hz), 4.96 (t, J = 10.7 Hz, 1H), 4.23‒4.05 (m, 4H), 2.86–2.70 (m, 2H), 2.18‒2.04 (m, 2H), 1.84‒1.70 (m, 1H), 1.31 (dt, J = 1.8 Hz and 7.1 Hz, 6H).

13C


137.7 (d, J = 16 Hz), 135.91 (d, J = 1.5 Hz), 128.7, 127.7 (d, J = 1.5 Hz), 127.6, 126.9, 68.0 (d, J = 4 Hz), 62.7 (d, J = 6.9 Hz), 62.51 (d, J = 6.5 Hz), 41.6 (d, J = 141.4 Hz), 29.1 (d, J = 14.6 Hz), 22.3 (d, J = 5.4 Hz), 16.9 (d, J = 5.4 Hz), 17.0 (d, J = 4.6 Hz). Anal. Calcd. for C14H21O4P: C, 59.15; H, 7.45. Found: C, 59.14; H, 7.41. 2-(Diphenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol (26a,b). Prepared according to the general procedure from 0.65 g (5.4 mmol) of benzocyclobutenol, 3 mL of 1.6 M n-BuLi (1.1 equiv), and 0.5 g (2.2 mmol) of diphenylvinylphosphine oxide (10) in 83 mL THF. The 1H NMR and

31P

NMR of the crude reaction mixture indicated complete conversion to the

desired product formed as a 4:6 (trans:cis) mixture of diastereoisomers. Silica gel chromatography of the mixture (5:1, chloroform:acetone) led to the isolation of 150 mg (0.431 mmol, 20%) of pure trans isomer as a white solid; 120 mg (0.348 mmol, 16 %) of pure cis isomer as a white solid, and 410 mg (1.18 mmol) (53%) of a mixture of the isomers. Cis-26a: white solid, mp 196‒197 oC.

31P

NMR (CDCl3, 121.5 MHz): δ 38.08 ppm. 1H

NMR (CDCl3, 300 MHz): δ 7.85‒7.61 (m, 4H), 7.51‒7.40 (m, 6H), 7.17‒7.02 (m, 4H), 4.92 (d, J = 5.4 Hz, 1H), 4.78 (s, 1H), 2.95‒2.88 (m, 1H), 2.78‒2.67 (m, 1H), 2.53-2.36 (m, 2H) 1.77‒1.61 (m, 1H). 13C NMR (CDCl3, 75.5 MHz): δ 137.1 (d, J = 11.5 Hz), 135.7 (bs), 132.2 (d, J = 2.7 Hz), 132.2 (d, J = 2.7 Hz), 131.5 (d, J = 97.6 Hz), 131.0 (d, J = 9.1 Hz, 2C), 130.8 (d, J = 97.6 Hz), 130.9 (d, J = 9.3 Hz, 2C), 129.9, 129.2, 129.0 (d, J = 11.7 Hz, 2C), 128.9 (d, J = 11.5 Hz, 2C), 128.4, 126.2, 67.1 (d, J = 4.1Hz), 39.2 (d, J = 72.1 Hz), 28.8 (d, J = 13.2 Hz), 16.8 Anal. Calcd. for C22H21O2P: C, 75.84; H, 6.08. Found: C, 75.54; H, 6.15. Trans-26b: white solid, mp 251‒252 oC.

31P


NMR (CDCl3, 300 MHz): δ 7.85‒7.75 (m, 4H), 7.62‒7.47 (m, 7H), 7.24‒7.12 (m, 2H), 6.99 (d, J = 7.4 Hz, 1H), 5.14 (t, J = 10.3 Hz, 1H), 5.12 (s, 1H, -OH), 3.03‒2.85 (m, 2H), 2.74‒2.64 (m, 1H), 2.02‒1.91 (m, 1H), 1.58‒1.42 (m, 1H). 13C NMR (CDCl3, 75.5 MHz): δ 138.0 (d, J = 11.7 Hz), 135.3 (bs), 132.7 (d, J = 2.6 Hz), 132.6 (d, J = 8.8 Hz, 2C), 132.4 (d, J


23


Page 24 of 39

= 2.6 Hz), 131.6 (d, J = 97.7 Hz), 131.3 (d, J = 9.1 Hz, 2C), 129.3 (d, J = 97.7 Hz), 129.1 (d, J = 11.6 Hz, 2C), 128.7 (d, J = 11.4 Hz, 2C), 128.3, 127.4, 127.3, 126.8, 68.1 (d, J = 3.4 Hz), 41.8 (d, J = 82.1 Hz), 29.0 (d, J = 12.9 Hz), 23.6. Anal. Calcd. for C22H21O2P: C, 75.84; H, 6.08. Found: C, 75.74; H, 5.92.

2-(Diphenylphosphinothioyl)-1,2,3,4-tetrahydronaphth-1-ol (27a,b). Prepared according to the general procedure from 0.15 g (1.25 mmol) benzocyclobutenol, 1.20 mL of 1.6 M nBuLi (1.1 equiv), and 0.2 g (0.82 mmol) of diphenylvinylphosphine sulfide (11) in 28 mL of THF. The 1H NMR and 31P NMR of the crude reaction mixture indicated 88% conversion to the desired product formed as a 13:1 (trans:cis) mixture of diastereoisomers. Silica gel chromatography (50:1, methylene chloride:methanol) of the mixture led to the isolation of 0.25 g (0.55 mmol, 67%) of a mixture of isomers (trans:cis, 30:1) as a white solid,

Trans-27b: white solid, mp 147‒148 oC.

31P

NMR (CDCl3, 1215 MHz): δ 48.09 ppm. 1H

NMR (CDCl3, 300 MHz): δ 8.00‒7.86 (m, 4H), 7.54‒7.44 (m, 7H), 7.23‒7.12 (m, 2H), 7.03 (d, J = 7.1 Hz, 1H), 5.34 (ddd, J = 4.3, 9.2 and 13.2 Hz, 1H), 3.30 (d, J = 4.4 Hz, 1H, -OH), 3.21‒3.11 (m, 1H), 2.93‒2.84 (m, 1H), 2.77-2.67 (m, 1H), 1.85-1.67 (m, 2H).

13C

NMR

(CDCl3, 75.5 MHz): δ 138.3 (d, J = 11.4 Hz), 135.8 (d, J = 1.5 Hz), 133.1 (d, J = 79.5 Hz), 132.2 (d, J = 9.7 Hz, 2C), 131.8 (d, J = 3 Hz), 131.7 (d, J = 3 Hz), 131.4 (d, J = 9.7 Hz, 2C), 130.5 (d, J = 78.6 Hz), 128.8 (d, J = 12 Hz, 2C), 128.7 (d, J = 11.9 Hz, 2C), 128.1, 127.3 (2C), 126.6, 68.9, 43.5 (d, J = 56.1 Hz), 28.9 (d, J = 13 Hz), 23.7. Anal. Calcd. for (mixture of isomers): C22H21OPS. C, 72.50; H, 5.81. Found: C, 72.67; H, 5.71. Cis-27a. 31P NMR (CDCl3, 121.5 MHz): δ 44.75 ppm. 1H NMR (CDCl3, 300 MHz): δ 4.95 (bd, J = 6.6 Hz, 1H), 4.63 (d, J = 1.3 Hz, 1H, -OH) (the only assigned signals in the mixture of isomers).

(Sp)-(-)-2-(Methylphenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol

(28a,b).

Prepared

according to the general procedure from 0.18 g (1.5 mmol) benzocyclobutenol, 1.2 mL 1.6 M n-BuLi (1.1 equiv), and 0.15 g (0.9 mmol) (Sp)-(-)-methylphenylvinylphosphine oxide 9 in 28 mL of THF. The 1H NMR and 31P NMR of this crude mixture indicated 99% conversion to the desired product formed as a 1:9 (trans:cis) mixture of diastereoisomers.

Silicagel

chromatography (40:1, methylene chloride:methanol) of the mixture led to the isolation of


24

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148 mg (0.52 mmol, 58%) of pure cis-28a as a white solid; and 64 mg (0.22 mmol, 24%) of a mixture of the isomers as a semi-solid. (Sp)-(-)-Cis-28a: white solid, mp 192-193 oC, []D20 ‒77.4 (c 2.15, CHCl3). 31P NMR (CDCl3, 121.5 MHz): δ 43.86 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.83‒7.77 (m, 2H), 7.60‒7.51 (m, 3H), 7.26‒7.03 (m, 4H), 4.98 (d, J = 3.6 Hz, 1H), 3.09‒3.01 (m, 1H), 2.86‒2.74 (m, 1H), 2.56‒2.41 (m, 1H), 2.19‒2.04 (m, 2H), 1.88 (d, J = 13.1 Hz, 3H). Anal. Calcd. for C17H19O2P: C, 71.32; H, 6.69. Found: C, 71.38; H, 6.66. (Sp)-trans-28c: 31P NMR (CDCl3, 121.5 MHz): δ 45.23 ppm. 1H NMR (CDCl3, 300 MHz): δ 5.08 (t, J = 10.8 Hz, 1H), 1.87 (d, J = 12.8 Hz, 3H) (the only assigned signals in the mixture of isomers). Reaction with 0.6 g (3.6 mmol) racemic methylphenylvinylphosphine oxide 9 as a dienophile gave a mixture of isomers trans:cis (1:9) at 99% conversion. Silicagel chromatography (40:1, methylene chloride:methanol) of the mixture led to the isolation 0.64 g (2.1 mmol, 58%) of pure cis-28a as a white solid, and 0.16 g (0.5 mmol, 14%) of a mixture of the isomers as a white solid. rac-cis-28a: white solid, mp 197‒198oC.

31P


NMR (CDCl3, 300 MHz): δ 7.80‒7.73 (m, 2H), 7.55‒7.44 (m, 3H), 7.26‒7.03 (m, 4H), 5.09 (d, J = 3.5 Hz, 1H), 5.04 (s, 1H,-OH), 2.96‒2.9 (m, 1H), 2.76‒2.64 (m, 1H), 2.37‒2.23 (m, 1H), 2.16‒2.08 (m, 1H), 1.92‒1.86 (m, 1H), 1.84 (d, J = 13.1 Hz, 3H).

13C

NMR (CDCl3,

75.5 MHz): δ 137.5 (d, J = 10.4 Hz), 135.3, 133.1 (d, J = 94.7 Hz), 131.7 (d, J = 2.6 Hz), 130.3 (d, J = 9 Hz, 2C), 129.8, 128.8, 128.5 (d, J = 11.3 Hz, 2C), 127.8, 126.1, 65.9 (d, J = 4.8 Hz), 42.0 (d, J = 72.1 Hz), 28.8 (d, J = 13.7 Hz), 17.2, 13.6 (d, J = 68.5 Hz, CH3). Anal. Calcd. for C17H19O2P (mixture of isomers): C, 71.32; H, 6.69. Found: C, 71.41; H, 6.69. rac-trans-28c

31P

NMR (CDCl3, 121,5 MHz): δ 44.9 ppm. 1H NMR (CDCl3, 300 MHz): δ

5.05 (t, J = 10.8 Hz, 1H), 1.88 (d, J = 12.8 Hz, 3H) (the only assigned signals in the mixture of isomers). 2-(tert-Butylphenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol (29). Prepared according to the general procedure from 0.52 g (4.3 mmol) of benzocyclobutenol, 1.2 mL of 1.6 M nBuLi (1.1 equiv), and 0.15 g (0.9 mmol) of rac-tert-butylphenylvinylphosphine oxide (13) in 83 mL of THF. The 1H NMR and

31P

NMR spectra of this crude mixture indicated 98%

conversion to the desired product formed as a mixture of four diastereoisomers (a pair of trans isomers and a pair of cis isomers 4:1). Silica gel chromatography (5:1, methylene


25


Page 26 of 39

chloride:acetone) of the mixture led to the isolation of 0.46 g (1.4 mmol, 48%) of pure major trans-isomer 29c as a white solid, and 180 mg (0.55 mmol, 18.7%) of a mixture of the three other isomers (minor trans and two cis isomers). The mixture was subjected to crystallization from methanol which afforded crystals of the minor trans isomer of 90% isomeric purity. Mother liquor contained mixture of major cis isomer, minor cis isomer and minor trans isomer (13.4:1:0.8) and this mixture was analyzed as such. trans-29c (major isomer): white solid, mp 211‒212 oC.

31P


52.62 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.94‒7.91 (m, 2H), 7.60‒7.51 (m, 4H), 7.20‒6.91 (m, 3H), 4.93 (t, J = 10.2 Hz, 1H), 4.41 (s, 1H, -OH), 2.96‒2.85 (m, 1H), 2.75‒2.61 (m, 2H), 2.75‒2.61 (m, 2H), 2.30‒2.13 (m, 1H), 1.62‒1.46 (m, 1H), 1.34 (d, J = 14.6 Hz, 9H).

13C

NMR (CDCl3, 75.5 MHz): δ 138.2 (d, J = 10.8 Hz), 135.0 (d, J = 0.8 Hz), 132.6 (d, J = 7.6 Hz, 2C), 132.1 (d, J = 3.8 Hz), 128.4 (d, J = 10.3 Hz, 2C), 128.3 (d, J = 81.8 Hz), 128.0, 127.5, 127.1, 126.6, 68.5 (d, J = 4.4 Hz), 40.0 (d, J = 61.4 Hz), 34.2 (d, J = 65.4 Hz), 29.2 (d, J =12.4 Hz), 25.2 (s, 3C), 24.8. Anal. Calcd. for (mixture of isomers) C20H25O2P: C, 73.15; H, 7.67. Found: C, 73.29; H, 7.57. Mixture of 29a,b,d: Anal. Calcd. for (mixture of isomers) C20H25O2P: C, 73.15; H, 7.67. Found: C, 73.31; H, 7.52. Trans-29d (minor trans isomer):

31P


(CDCl3, 300 MHz): δ 7.82 (bt, J = 8.2, 2H), 7.57‒7.47 (m, 4H), 7.17‒7.02 (m, 3H), 5.25 (t, J = 9.1 Hz, 1H), 4.64 (s, 1H, -OH), 2.97-2.87 (m, 2H), 2.83-2.68 (m, 1H), 2.58‒2.48 (m, 1H), 2.32‒2.12 (m, 1H), 1.26 (d, J = 14.3 Hz, 9H). 13C NMR (CDCl3, 75.5 MHz): δ 138.3 (d, J = 8.9 Hz), 135.7 (bs), 132.2 (d, J = 84 Hz), 131.7 (d, J = 2.6 Hz), 131.4 (d, J = 7.8 Hz, 2C), 128.4 (d, J = 10.7 Hz, 2C), 128.2, 128.0, 127.3, 126.6, 69.2 (d, J = 2.5 Hz), 44.5 (d, J = 60.7 Hz), 35.1 (d, J = 64 Hz), 29.4 (d, J = 10.7 Hz), 25.8 (s, 3C), 23.7 (d, J = 2.3 Hz). Cis-29a (major cis isomer): 31P NMR (CDCl3, 121.5 MHz): δ 56.26 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.74‒7.68 (m, 2H), 7.58‒7.50 (m, 3H), 7.38‒7.35 (m, 1H), 7.24‒7.06 (m, 3H), 5.44 (bs, 1H), 2.95‒2.8 (m, 1H), 2.78‒2.7 (m, 1H), 2.5 (dt, J = 2.5 Hz, 13.1 Hz, 1H), 2.38‒2.16 (m, 1H), 1.66‒1.57 (m, 1H,), 1.28 (d, J = 14.4 Hz, 9H, CH3).

13C

NMR (CDCl3,

75.5 MHz): δ 137.0 (d, J = 10.2 Hz), 135.5 (d, J = 0.8 Hz), 131.7 (d, J = 3.6 Hz), 131,3 (d, J = 7.8 Hz, 2C), 129.8, 129.3 (d, J = 86 Hz), 128.9, 128.4 (d, J = 10.8 Hz, 2C), 128.1, 126.1, 68.5 (d, J = 4.4 Hz), 40.0 (d, J = 61.4 Hz), 34.2 (d, J = 65.4 Hz), 29.2 (d, J = 12.4 Hz), 25.2 (s, 3C), 24.8.


26

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(rac)-cis-29b (minor cis isomer).

31P


(CDCl3, 300 MHz): δ 4.64 (bd, J = 5.7 Hz, 1H), 1.05 (d, J = 15.2 Hz, 9H) (the only assigned signals in the mixture of isomers). The

same

cycloaddition

reaction

carried

out

with

the

resolved

(RP)-(-)-tert-

butylphenylvinylphosphine oxide [0.11 g, 0.335 mmol, []D = -70.5 (1.15, CHCl3)] as the dienophile gave a mixture of trans:cis isomers (4:1) at 98% conversion. Silica gel chromatography (15:1, chloroform:methanol) of the mixture led to the isolation 0.033 g (0.1 mmol, 30%) of pure major trans-isomer as a white solid, and 0.05g (0.15 mmol, 45%) of a mixture of the other isomers. trans-(RP)-(+)-29c (major isomer): white solid, mp 187‒188 oC. []D20 +19.1 (c 1.1, CHCl3). 31P

NMR (CDCl3, 121.5 MHz): δ 52.91 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.96‒7.90 (m,

2H), 7.62‒7.51 (m, 4H), 7.19‒6.97 (m, 3H), 4.94 (t, J = 10.2 Hz, 1H), 2.96‒2.85 (m, 1H), 2.74‒2.61 (m, 1H), 2.21‒2.13 (m, 1H), 1.62‒1.48 (m, 1H), 1.34 (d, J = 14.6 Hz, 9H). Crystal data for rac-29c: crystal system monoclinic, space group P21/c, unit cell dimensions a = 13.232(2) Å, b = 9.075(1) Å, c = 15.852(3) Å, β = 113.34(2)°, volume = 1747.7(5) Å3, Z = 4, density (calcd) = 1.248 g/cm3, absorption coeff. 1.44 mm-1, F(000) = 704, theta range for data collection 3.64 to 76.40°, index ranges -16  h  16, -11  k  8, -19  l  17; reflections collected/ independent 11732 / 3616. Goodness-of-fit on F2 = 1.118; final R indices [I>2(I)] R1 = 0.0381, wR2 = 0.1009;  max./min. 0.36 / -0.48 e.Å-3.

2-[(2-Methoxyphenyl)phenylphosphinoyl]-1,2,3,4-tetrahydronaphth-1-ol (30). Prepared according to the general procedure from 0.20 g (1.67 mmol) of benzocyclobutenol, 0.50 mL 1.6 M n-BuLi (1.1 equiv.), and 0.20 g (0.775 mmol) o-anisylphenylvinylphosphine oxide (11) in 23 mL of THF. The 1H NMR and

31P

NMR of the crude reaction mixture indicated 66%

conversion affording the desired product as a mixture of four diastereoisomers (a pair of trans isomers and a pair of cis isomers 7:3). Silica gel chromatography (6:1, methylene chloride:acetone) of the mixture led to the isolation of 20 mg (0.053 mmol, 7%) of pure major trans-isomer 30c as a semi-solid, and three mixed fractions of various composition of the remaining isomers and the substrate. trans-30c (major isomer): semi-solid;

31P


NMR (CDCl3, 300 MHz): δ 8.05‒6.84 (m, 13H), 5.33 (t, J = 9.8 Hz, 1H), 3.74 (s, 3H, CH3) 3.19‒3.09 (m, 1H), 2.95‒2.76 (m, 2H), 2.03‒1.74 (m, 2H). 13C NMR (CDCl3, 75.5 MHz): δ 159.2 (d, J = 5 Hz), 137.5 (d, J = 12.7 Hz), 136.0, 134.4 (d, J = 2 Hz), 134.3 (d, J = 7.1 Hz),


27


Page 28 of 39

132.4 (d, J = 98 Hz), 132.0 (d, J = 2.7 Hz), 131.1 (d, J = 9.5 Hz, 2C), 130.0, 129.3, 128.6 (d, J = 11.7 Hz, 2C), 128.3, 126.2, 121.9 (d, J = 10.7 Hz), 119.0 (d, J = 96.4 Hz), 110.8 (d, J = 7 Hz), 67.1 (d, J = 4.1 Hz), 55.4 (s, 3C), 38.6 (d, J = 73.3 Hz), 29.2 (d, J = 14 Hz), 16.7. MS (EI HR) for C23H23O3PNa [M + Na]+: calcd. 401.1277, found 401.1269. The remaining isomers were analyzed only in mixtures to possibly identify the assignable signals of the individual isomers. trans-30d (minor isomer).

31P

NMR (CDCl3, 121.5 MHz): δ 39.26 ppm. 1H NMR (CDCl3,

300 MHz): δ 8.00‒6.93 (m, 13H), 5.15 (t, J = 10.3 Hz, 1H), 3.82 (s, 3H) 3.18‒2.75 (m, 3H), 2.03‒1.95 (m, 2H) (signals assigned in the mixture of isomers). cis-30a (major isomer). 31P NMR (CDCl3, 121.5 MHz): δ 39.94 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.10‒6.82 (m, 13H), 5.35 (s, 1H –OH), 5.05 (bd, J = 5.4 Hz, 1H), 3.86 (s, 3H, CH3), 3.04 (dt, J = 3.0 Hz and 9.0 Hz, 1H), 2.93‒2.77 (m, 2H), 2.59‒2.44 (m, 1H), 1.85-1.81 (m, 1H) (signals assigned in the mixture of isomers). cis-30b (minor isomer). 31P NMR (CDCl3, 121.5 MHz): δ 38.92 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.21‒6.90 (m, 13H), 4.92 (bd, J = 3.8 Hz, 1H), 3.82 (s, 3H) (signals assigned in the mixture of isomers).

2-((Naphth-1-yl)phenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol

(31).

Prepared

according to the general procedure from 0.13 g (1.08 mmol) of benzocyclobutenol, 0.6 mL of 1.6 M n-BuLi, and 0.14 g (0.5 mmol) of 1-naphthylphenylvinylphosphine oxide (15) in 22.5 mL of THF. The 1H NMR and

31P

NMR of the crude reaction mixture indicated 95%

conversion to the desired product formed as a mixture of four diastereoisomers (a pair of trans isomers and a pair of cis isomers, 4:6). Silicagel chromatography (6:1, methylene chloride:acetone) of the mixture led to the isolation 10 mg (0.025 mmol) (5%) pure major trans-isomer 31c as a white solid, and three mixtures of isomers with various composition.

trans-31c (major isomer): white solid, mp 195‒196 oC.

31P


41.79 ppm, 1H NMR (CDCl3, 300 MHz): δ 8.35 (d, J = 8.7 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.99 (ddd, J = 0.9 Hz, 7.1 Hz and 14.1 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.74‒7.67 (m, 3H), 7.59 (ddd, J = 2.8 Hz, 4.4 Hz and 8.2 Hz, 1H), 7.52‒7.39 (m, 5H), 7.27‒7.23 (m, 1H), 7.15 (dt, J = 1.0 Hz and 7.4 Hz, 1H), 7.01 (d, 1H, J = 7.3 Hz), 5.83 (s, 1H, -OH), 5.30 (t, J =11.4 Hz, 1H), 3.30‒3.18 (m, 1H), 3.02-2.91 (m, 1H), 2.7‒2.6 (m, 1H), 2.08‒1.98 (m, 1H),


28

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1.44‒1.30 (m, 1H). 13C NMR (CDCl3, 75.5 MHz): δ 138.1 (d, J = 12 Hz), 135.1 (d, J = 1.2 Hz), 134.2 (d, J = 8.6 Hz), 133.9 (d, J = 2.8 Hz), 133.3 (d, J = 7.1 Hz,), 132.2 (d, J = 2.8 Hz), 131.9 (d, J = 9.8 Hz, 2C), 130.9 (d, J = 10 Hz), 130.4 (d, J = 103 Hz), 129.1 (d, J = 1.1 Hz), 128.7 (d, J = 11.7 Hz, 2C), 128.1, 127.6, 127.3, 127.1, 126.9 (d, J = 6.1 Hz), 126.7, 126.6, 126.4 (d, J = 96.5 Hz), 124.2 (d, J = 13.5 Hz), 67.8 (d, J = 3.5 Hz), 41.2 (d, J = 72.3 Hz), 28.8 (d, J = 12.8 Hz), 24.3. Anal. Calcd. for C26H23O2P: C, 78.38; H, 5.82. Found: C, 78.57; H, 6.03. The remaining isomers were analyzed only as mixtures to possibly identify the assignable signals of the individual isomers. trans-31d (minor isomer): 31P NMR (CDCl3, 121.5 MHz): δ 42.85 ppm. 1H NMR (CDCl3, 300 MHz): δ 5.44 (t, J =10 Hz, 1H) (signals assigned in a mixture of isomers). cis-31a (major isomer):

31P

NMR (CDCl3, 121.5 MHz): δ 42.25 ppm. 1H NMR (CDCl3, 300

MHz): δ 5.4 (dd, J =3 Hz and 14.5 Hz, 1H) (signal assigned in a mixture of isomers). cis-31b (minor isomer): 31P NMR (CDCl3, 121.5 MHz): δ 42.62 ppm. 1H NMR (CDCl3, 300 MHz): δ 5.06 (dd, J = 3Hz and 11 Hz, 1H) (signal assigned in a mixture of isomers).

2-(Diphenylphosphinoyl)-3-phenyl-1,2,3,4-tetrahydronaphth-1-ol (32). To a cooled (-78 oC)

solution of 0.08 g (0.66 mmol) benzocyclobutenol in 15 mL THF, 0.45 mL 1.6 M n-BuLi

(1.1 equiv), and 0.1 g (0.33 mmol) ((E)-2-phenylvinyl)diphenylphosphine oxide 32 in 2 mL THF. The 1H NMR and

31P

NMR of this crude mixture indicated 75% conversion to the

desired product formed as a mixture of two diastereoisomers: trans and cis (16:1). Silica gel chromatography (15:1, methylene chloride:methanol) of the mixture led to the isolation mixture of isomers. Crystallization of the mixture of isomers from methanol gave pure trans isomer 38 mg (0.09 mmol) (27%) as white crystals. From the mother liquor a 10:1 mixture of trans and cis isomers was obtained and was analyzed further. trans-32b: white crystals, mp 237‒238 oC. 31P NMR (CDCl3, 121.5 MHz): δ 39.25 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.74‒7.68 (m, 2H), 7.62‒7.55 (m, 3H), 7.5‒7.28 (m, 7H), 7.18‒7.12 (m, 1H), 7.06‒6.98 (m, 3H), 6.87 (d, J = 7.3 Hz, 1H), 6.60‒6.56 (m, 2H), 5.21 (dd, J = 7.3 Hz and 12.3 Hz, 1H), 3.4 (dq, J = 5.6 Hz and 20.4 Hz, 1H), 3.20 (ddd, J = 5.8 Hz, 7.3 Hz and 10.9 Hz, 1H), 2.65 (dq, J = 5.8 Hz, 14.6 Hz, 2H). 13C NMR (CDCl3)  145.8 (d, J = 5.2 Hz), 139.3 (d, J = 9 Hz), 135.6, 132.5 (d, J = 8.7 Hz, 2C), 132.4 (d, J = 2.5 Hz, 2C), 131.4 (d, J = 2.5 Hz, 2C), 132.3 (d, J = 98.8 Hz), 130.7 (d, J = 98.8 Hz), 131.7, 131.4, 129.1 (d, J =


29


Page 30 of 39

11.8 Hz, 2C), 129.0 (d, J = 11.8 Hz, 2C), 128.7 (s, 2C), 128.1 (d, J = 17.8 Hz, 2C), 127.9 (d, J = 17.8 Hz, 2C), 127.3, 126.8, 125.3, 68.0, 48.5 (d, J = 68 Hz), 40.2, 36.7 (d, J = 5.2 Hz). MS (HR ESI) for C28H25O2PNa [M + Na]+ calcd 447.1484. Found: 447.1490. 3'-(Diphenylphosphinoyl)-1',2',3',4'-tetrahydro-1,2'-binaphth-4'-ol

(33).

Prepared

according to the general procedure from 0.13 g (1.1 mmol) of benzocyclobutenol in 15 mL THF, 0.8 mL 1.6 M n-BuLi (1.1 equiv), 0.19 g (0.54 mmol) 1-[(E)-2-(diphenylphosphinoyl) vinyl]naphthalene 19 in 3 mL of THF. The 1H NMR and

31P

NMR of this crude mixture

indicated 98% conversion to the desired product formed as a mixture of two diastereoisomers: trans and cis (9:1). Silicagel chromatography (15:1, methylene chloride:methanol) of the mixture led to the isolation of a mixture of isomers. Crystallization of this mixture from methanol gave 100 mg (0.21mmol, 26%) of pure trans-33b as white crystals. The mother liquor contained a mixture of trans and cis isomer which was analyzed by 31P and 1H NMR to possibly extract the signals of the cis isomer. trans-33b: white crystals, mp 180‒181 oC. 31P NMR (CDCl3, 121.5 MHz): δ 39.52 ppm. 1H NMR (CDCl3, 300 MHz):  7.73 (d, J = 8 Hz, 1H), 7.76‒7.57 (m, 7H), 7.47‒7.1 (m, 11H), 6.85 (d, J = 7.1 Hz, 1H), 6.77 (d, J = 7.3 Hz, 1H), 5.34 (dd, J = 7 Hz and 12.7 Hz, 1H), 4.33 (bd, J = 15.1 Hz, 1H), 3.49 (bs, 1H), 2.77 (d, J = 4.1 Hz, 2H). 13C NMR (CDCl3, 75.5 MHz): δ 141.2, 139.0 (d, J = 9.6 Hz), 135.6, 134.1, 133.0-125.1, 133.0, 132.3, 132.2, 132.2, 131.7, 131.5, 131.4, 131.4, 131.0, 130.0, 129.3, 129.1, 128.9, 128.7, 128.6, 128.3, 127.8, 127.5, 127.4, 126.5, 125.7, 125.6, 125.1, 122.6, 68.0, 48.5 (d, J = 70.7 Hz), 35.7 (d, J = 4.8 Hz), 33.7. MS (EI HR) for C32H27O2P [M+·]: calcd 474.17487. Found: 474.17377. cis-33a:

31P

NMR (CDCl3, 121.5 MHz): δ 39.35 ppm. 1H NMR (CDCl3, 300 MHz):  5.21

(bd, J = 7 Hz, 1H) (the only assigned signals in the mixture of isomers).

3'-(Diphenylphosphinoyl)-2-methyl-1',2',3',4'-tetrahydro-1,2'-binaphth-4'-ol

(34).

Prepared according to the general procedure from 0.10 g (0.83 mmol) of benzocyclobutenol, 0.6 mL of 1.6 M n-BuLi (1.1 equiv.), and 0.15 g (0.41 mmol) of 1-[(E)-2(diphenylphosphinoyl)vinyl]-2-methyl-naphthalene (20) in 18 mL of THF. The 1H NMR and 31P

NMR of the crude reaction mixture indicated 55% conversion to the desired product

formed as a mixture of trans and cis (3:2) isomers. Silica gel chromatography (5:1, methylene chloride:acetone) of the mixture led to the isolation of two mixtures: a mixture of isomer trans:cis 2:1 (40 mg, 0.082 mmol, 20%) in the first fraction, and a mixture of the two isomers


30

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with the substrate in the second fraction. The first fraction (semisolid) was subjected to NMR and MS analysis. MS (EI HR) for C33H29O2P [M+·](mixture of isomers): calcd: 488.19052. Found: 488.19036. trans-34b: semi-solid;

31P

NMR (CDCl3, 121.5 MHz): δ 33.40 ppm. 1H NMR (CDCl3, 300

MHz): δ 8.9 (d, J = 8.6 Hz, 1H), 7.86‒6.61 (m, 19 H), 5.27 (dd, J = 2 Hz and 12.1 Hz, 1H), 4.34 (bt, J = 8.0 Hz, 1H), 4.23‒4.18 (m, 1H), 3.97 (t, J = 14.7 Hz, 1H), 2.8 (dd, J = 3.9 Hz and 14.7 Hz, 1H), 2.15 (s, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 138.8-123.7 (28 C signals for the two isomers: 138.8, 137.9 (d, J = 2.6 Hz), 137.2, 137.0, 136.5, 136.1, 135.7, 135.6, 136.5 (d, J = 2 Hz), 135.1, 134.4, 133.7, 133.65, 133.6, 133.4, 133.1, 133.2, 133.1, 132.8, 131.5, 131.4, 131.2, 130.82, 130.78, 130.7, 130.5, 130.4, 130.3, 130.2, 130.1, 129.7, 129.5, 129.41, 129.36, 129.2, 129.1, 128.8, 128.7, 128.7, 128.6, 128.6, 128.5, 128.4, 128.2, 128.0, 127.9, 127.9, 127.8, 127.4, 127.4, 127.3, 127.1, 127.08, 127.05, 126.9, 126.8, 126.2, 125.8, 125.4, 125.2, 124.7, 124.4, 124.2, 123.9, 123.7), 70.6 (d, J = 3.6 Hz), 44.0 (d, J = 71.1 Hz), 35.8, 34.5 (d, J = 9.6 Hz), 21.9 (CH3). cis-34a:

31P

NMR (CDCl3, 121.5 MHz): δ 36.72 ppm. 1H NMR (CDCl3, 300 MHz): δ

7.86‒6.61 (m, 20 H), 5.14‒5.10 (m, 1H), 5.04 (dd, J = 1.3 Hz and 7.1 Hz, 1H), 3.66‒3.61 (m, 1H), 3.57 (dd, J = 9.5 Hz and 17.9 Hz, 1H), 3.45 (dd, J = 8.1 Hz and 17.9 Hz, 1H), 2.10 (s, 3H).

13C

NMR (CDCl3, 75.5 MHz): δ 138.8-123.7 (28 C signals for the isomers 138.8, 137.9

(d, J = 2.6 Hz), 137.2, 137.0, 136.5, 136.1, 135.7, 135.6, 136.5 (d, J = 2 Hz), 135.1, 134.4, 133.7, 133.65, 133.6, 133.4, 133.1, 133.2, 133.1, 132.8, 131.5, 131.4, 131.2, 130.82, 130.78, 130.7, 130.5, 130.4, 130.3, 130.2, 130.1, 129.7, 129.5, 129.4, 129.3, 129.2, 129.1, 128.8, 128.71, 128.67, 128.63, 128.58, 128.5, 128.4, 128.2, 128.0, 127.9, 127.86, 127.8, 127.43, 127.41, 127.3, 127.1, 127.1, 127.0, 126.9, 126.8, 126.2, 125.8, 125.4, 125.2, 124.7, 124.4, 124.2, 123.9, 123.7), 70.0 (d, J = 3.7 Hz), 40.9 (d, J = 70 Hz), 34.1 (d, J = 10.2 Hz), 28.8, 21.7. 2-(Diphenylphosphinoyl)-3-[2-(diphenylphosphinoylmethyl)phenyl]-1,2,3,4-tetrahydronaphth-1-ol (35). Prepared according to the general procedure from 0.10 g (0.83 mmol) of benzocyclobutenol, 0.6 mL of 1.6 M n-BuLi (1.1 equiv), and 0.10 g (0.193 mmol) of 1-(diphenylphosphinoylmethyl)-2-[(E)-2-(diphenylphosphinoyl)vinyl]benzene (21) in 23 mL of THF. The 1H NMR and

31P

NMR of the crude reaction mixture indicated 99% conversion to the

desired product formed as a mixture of two trans and cis (18:1) isomers. Silicagel


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chromatography (5:1, methylene chloride:acetone) of the mixture led to the isolation 98 mg (0.15 mmol, 78%) of pure trans-35b. trans-35b: white solid, mp 159‒160 oC.

31P

NMR (CDCl3, 121.5 MHz): δ 36.23 ppm and

29.19 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.70‒7.11 (m, 23 H), 6.92‒6.78 (m, 5H), 5.07 (dd, J = 5.3 Hz and 11.8 Hz, 1H), 3.7 (s, 1H, -OH), 3.68‒3.54 (m, 1H), 3.45‒3.28 (m, 2H), 3.45‒3.28 (m, 2H) 2.77 (t, J = 15 Hz, 1H), 2.6‒2.54 (m, 1H), 2.26 (dd, J = 5.6 Hz and 14.8 Hz, 1H).

13C

NMR (CDCl3, 75.5 MHz): δ 144.7 (m), 138.3 (d, J = 6.3 Hz), 136.7,

133.7‒131.1 (21 signals: 133.7, 133.3, 133.2, 132.7, 132.5, 132.4, 131.9, 131.9, 131.8, 131.8, 131.7, 131.6, 131.5, 131.4, 131.4, 131.4, 131.2, 131.2, 131.1, 131.1, 130.8), 129.1 (d, J = 7.7 Hz), 128.7-128.2 (7 signals: 128.7, 128.7, 128.6, 128.6, 128.5, 128.3, 128.2), 127.4, 127.4 (d, J = 2.6 Hz), 126.7, 126.1, 126.1, 68.3, 49.3 (d, J = 67.6 Hz), 35.4 (d, J = 5.8 Hz, C4), 34.4, 33.5 (d, J = 66.9 Hz). Anal. Calcd. for C41H36O3P2: C, 77.10; H, 5.68. Found: C, 76.81; H, 5.45.

2-Methyl-3'-(methylphenylphosphinoyl)-1',2',3',4'-tetrahydro-1,2'-binaphth-4'-ol (36). Prepared according to the general procedure from 0.81 g (6.75 mmol) of benzocyclobutenol 8.5 mL of 1.6 M n-BuLi (1.1 equiv), and 0.84 g (2.74 mmol) of (Sp)-(-)-(2-methyl-1-[(E)-2(methylphenyl-phosphinoyl)vinyl]naphthalene (Sp)-(-)-23 in 156 mL of THF. The 1H NMR and

31P

NMR of the crude reaction mixture indicated complete conversion to the desired

product formed as a mixture of trans and cis (1:16) isomers. Silicagel chromatography (5:1, methylene chloride:acetone) led to the isolation of a 1:12 trans:cis mixture of isomeric products (0.81 g, 1.9 mmol, 70%); a solid which was analyzed as a mixture. A solid, mp 247‒248 oC. []D20 +110.4 (c 1.45, CHCl3). Anal. Calcd. for C28H27O2P (mixture of isomers): C, 78.85; H, 6.38. Found: C, 78.69; H, 6.34. cis-36a: solid;

31P


7.96 (dd, J = 2 Hz and 8.2 Hz, 1H), 7.88‒7.85 (m, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.57‒7.11 (m, 13H), 5.19‒5.09 (m, 1H), 4.80 (dd, J = 1.4 Hz and 7 Hz, 1H), 3.66 (dd, J = 10.0 Hz and 18.0 Hz, 1H), 3.46 (dd, J = 8.5 Hz and 17.8 Hz, 1H), 3.18 (ddd, J = 1.7 Hz, and 5.4 Hz, and 12.8 Hz, 1H), 2.84 (s, 3H), 0.45 (d, J = 13.3 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 136.7 (d, J = 10.2 Hz), 135.9, 135.8 (d, J = 2.3 Hz), 135.7 (d, J = 1 Hz), 133.7, 133.0 (d, J = 93.6 Hz), 132.1, 131.8 (d, J = 2.7 Hz), 130.0 (d, J = 10.7 Hz, 2C), 129.9 (d, J = 8.9 Hz, 2C), 129.3, 129.0, 128.8, 128.7, 128.6, 128.0, 126.1, 125.7, 124.5, 124.2, 69.2 (d, J = 4.3 Hz), 44.4 (d, J = 68.8 Hz), 33.7 (d, J = 10.5 Hz), 29.5 (C2’), 21.8, 16.0 (d, J = 66.7 Hz).


32

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trans-36b: 31P NMR (CDCl3, 121.5 MHz): δ 45.98 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.5 (d, J = 8.6 Hz, 1H), 2.3 (s, CH3), 0.97 (d, J = 13.3 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 137.2 (d, J = 10.3 Hz), 136.0, 134.6, 134.2, 132.8, 132.6, 131.4, 130.7, 128.5, 128.5, 128.3, 126.9, 126.2, 125.1, 123.5, 66.1, 35.1, 27.8, 21.9, 15.2. (the only assigned signals in the mixture of isomers). The same reaction carried out with racemic 23 gave 0.83 g (1.95 mmol, 71%) of an analogous 1:16 mixture of racemic trans and cis cycloadducts.

2-Isopropoxy-3'-(methylphenylphosphinoyl)-1',2',3',4'-tetrahydro-1,2'-binaphth-4'-ol (37). Prepared according to the general procedure from 0.07 g (0.58 mmol) benzocyclobutenol in 15 mL THF, 0.5 mL of 1.6 M n-BuLi (1.1 equiv), and 0.10 g (0.285 mmol) of 2-isopropoxy-1-[(E)-2-(methylphenyl-phosphinoyl)vinyl]naphthalene (29) in 17 mL of THF. The 1H NMR and 31P NMR of the crude reaction mixture indicated 97% conversion to the desired product formed as a mixture of two diastereoisomers: trans and cis (1:8.3). Silicagel chromatography (5:1, methylene chloride:acetone) of the mixture led to the isolation of 0.106 g (0.226 mmol, 79%) of the cycloadducts 37 as a 1:8 mixture of trans and cis isomer as a semi-solid which was analyzed as such. Anal. Calcd. for C30H31O3P (mixture of isomers): C, 76.57; H, 6.64. Found: C, 76.47; H, 6.64. cis-37a: 31P NMR (CDCl3, 121.5 MHz): δ 47.06 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.31 (d, J = 8.7 Hz, 1H), 7.8‒7.32 (m, 2H), 7.56‒7.50 (m, 1H), 7.44‒7.05 (m, 11H), 5.18 (bd, J = 8 Hz, 1H), 5.09 (d, J = 2.2 Hz, 1H, -OH), 4.93‒4.81 (m, 1H), 4.58 (septet, J = 6 Hz, 1H), 3.55‒3.40 (m, 2H), 3.17‒3.08 (m, 1H), 1.26 (d, J = 6.0 Hz, 3H, CH3), 1.21 (d, J = 6 Hz, 3H), 1.08 (d, J = 13.4 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 154.0, 137.5 (d, J = 10 Hz), 137.0, 134.4 (d, J = 94.1 Hz), 133.3, 131.4 (d, J = 2.4 Hz), 130.0 (d, J = 9 Hz, 2C), 129.2, 129.1, 128.8 (d, J = 5.5 Hz, 2C), 128.5, 128.4, 128.3, 128.1, 127.4, 126.1, 123.6, 123.5 (d, J = 2.6 Hz), 122.9, 114.1, 69.4, 69.2 (d, J = 4.8 Hz), 43.0 (d, J = 69.4 Hz), 34.2 (d, J = 10.6 Hz), 28.0, 22.9, 21.8, 15.2 (d, J = 66.3 Hz). trans-37b:

31P


7.71‒7.67 (m, 3H), 7.44‒7.05 (m, 12H), 5.43‒5.46 (m, 1H), 5.23‒5.20 (m, 1H), 5.05 (d, J = 1.8 Hz, 1H, -OH), 4.72 (septet, J = 6 Hz, 1H), 3.47‒3.38 (m, 2H), 3.22‒3.16 (m, 1H), 1.53 (d, J = 6 Hz, 3H), 1.39 (d, J = 6 Hz, 3H), 1.10 (d, J = 13.5 Hz, 3H) (the only signals assigned in the mixture of isomers).

13C

NMR (CDCl3, 75.5 MHz): δ 153.5, 130.2, 129.7, 129.6, 129.4,


33


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128.6, 125.7, 124.0, 123.3, 116.7, 72.3, 43.6, 25.3, 22.6, 14.7 (d, J = 66.5 Hz) (the only signals assigned in the mixture of isomers).

2-Methyl-3'-(methylphenylphosphinoyl)-1',2'-dihydro-1,2'-binaphthyl (38a,b) Synthesis with PBr3. In 25 mL round bottom flask equipped with a septum, an argon inlet, and a magnetic stirrer 140 mg (0.33 mmol) of phosphine oxide 36a,b (16:1) in 5 mL of chloroform was placed. Next, 0.35 mL (3.5 mmol) of PBr3 was added via septum and the mixture was stirred at room temperature for 72 h. Then, water (5 mL) was added to the reaction mixture, organic layer was washed 5% potassium carbonate (5 mL) and water (5 mL). Organic layer was dried over MgSO4, evaporated under reduced pressure, and the residue was purified using column chromatography with methylene chloride:methanol (50:1) as eluent affording 38a,b (3.3:1) as a white solid (90 mg, 65%). Synthesis with mesyl chloride. In 50 mL round bottom flask equipped with a septum, an argon inlet, and a magnetic stirrer 36a,b (16:1) (97 mg, 0.23 mmol) in 2 mL of THF was placed. Mixture was cooled to – 15 oC and triethylamine (0.4 mL, 2.87 mmol) was added dropwise followed by mesyl chloride (0.06 mL, 0.776 mmol). After 1.5 h the reaction mixture was allowed to warm up to room temperature and then chloroform (30 mL) was added. Organic layer was washed with 5% HCl (5 mL), 5% sodium carbonate (5 mL), water (5 mL) and dried over MgSO4. Solvents were evaporated and the residue was purified using column chromatography with methylene chloride:methanol (50:1) as eluent affording 38a,b (3.3:1) as a white solid (0.063g, 67%). Synthesis with CeCl3*7H2O/NaI. A mixture of 0.08 g (0.19 mmol) 36a,b (16:1), 0.069 g (0.45 mmol) NaI, 0,1 g (0,281 mmol) CeCl3*7H2O in 10 mL of acetonitrile was heated to refluxed for 24 h. After cooling to the room temperature, solvent was evaporated and the residue was dissolved in 30 mL of chloroform, washed with 5% HCl (5 mL), 5 % solution Na2SO3 (5 mL), water (5 mL) and dried over MgSO4. Solvent was evaporated and the residue was purified by silicagel chromatography (50:1, methylene chloride:methanol) giving 0.06g (0.146 mmol, 91%) 38a,b


34

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(3.3:1) as a white semi-solid. As all attempts to separate this mixture failed it was subjected to NMR and elemental analysis as was. 38a: 31P NMR (CDCl3, 121.5 MHz): δ 32.19 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.11 (d, J = 8.6 Hz, 1H), 7.68‒7.55 (m, 2H), 7.31‒6.95 (m, 13H), 5.11‒5.01 (m, 1H), 3.59 (dd, J = 13.0 Hz and 17.3 Hz, 1H), 3.29‒3.16 (m, 1H), 2.59 (s, 3H), 1.12 (d, J = 13.3 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 138.3 (d, J = 9.1 Hz), 136.8 (d, J = 94.0 Hz), 135.7 (d, J = 2.1 Hz), 135.1 (d, J = 2.3 Hz), 134.4, 133.6, 133.2 (d, J = 101.5 Hz), 132.5, 133.2 (d, J = 2.7 Hz), 133.2 (d, J = 14.6 Hz),130.1 (d, J = 9.5 Hz, 2C), 129.9, 129.4, 129.0, 129.0, 128.0, 127.9 (d, J = 11.8 Hz, 2C), 127.6, 126.7 (d, J = 0.9 Hz), 126.0, 125.2, 124.4, 36.7 (d, J = 9.1 Hz), 33.9 (d, J = 7.2 Hz), 21.3, 15.5 (d, J = 72.8 Hz). 38b:

31P

NMR (CDCl3)  29.54 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.96‒7.93 (m, 1H),

7.85‒7.73 (m, 1H), 7.68‒7.54 (m, 2H), 7.45‒7.40 (m, 2H), 7.28‒6.96 (m, 9H), 6.85 (d, J = 8.4 Hz, 1H), 5.26‒5.18 (m, 1H), 3.29‒3.16 (m, 2H), 2.08 (s, 3H), 1.54 (d, J = 13.0 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 139.5 (d, J = 7.2 Hz), 137.0, 135.8, 135.1, 134.5, 134.5, 134.4, 132.5, 132.2, 131.7, 131.5, 131.0 (d, J = 2.8 Hz), 130.9, 130.2, 130.1, 129.8, 128.8, 127.8, 127.6, 127.6, 127.5, 127.1, 126.7, 124.7, 122.2, 34.5 (d, J = 9.9 Hz), 34.0 (d, J = 7.7 Hz), 22.1, 15.2 (d, J = 73.2 Hz). Anal. Calcd. for C28H25OP (mixture of 38a,b): C, 82.33; H, 6.17; Found C, 82.22; H, 6.03. 2-Methyl-3'-(methylphenylphosphinoyl)-1,2'-binaphthyl (39a,b). A mixture of 38a,b (0.5 g, 1.32 mmol) and DDQ (1.045 g, 4.6 mmol) in dioxane (10 mL) was heated at 120 oC for 48 h. After cooling, precipitate was filtered and solvent was evaporated. Silicagel chromatography (20:1, methylene chloride:metanol) of the crude led to the isolation of 0.46 g (0.14 mmol, 92%) of 39a,b as a 1.2:1 mixture of two diastereomers. Fractional crystallization of this mixture from 100 mL of acetone gave pure 39a (120 mg, 24%) and pure 39b (80 mg, 16%). 39a (major): white solid, mp 209‒210 oC. 31P NMR (CDCl3, 121.5 MHz): δ 30.10 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.83 (d, J = 14.3 Hz, 1H), 8.07‒8.02 (m, 1H), 7.84‒7.8 (m, 2H), 7.73 (d, J = 8.1 Hz, 1H), 7.66‒7.60 (m, 3H), 7.42 (d, J = 8.4 Hz, 1H), 7.25‒7.18 (m, 2H), 7.11‒7.01 (m, 4H), 6.82‒6.80 (m, 1H), 6.66 (d, J = 8 Hz, 1H), 2.21 (s, 3H), 1.42 (d, J = 13.4 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 137.5 (d, J = 10.9 Hz), 135.9 (d, J = 2.5 Hz), 135.8 (d, J = 8.4 Hz), 134.9, 134.7, 134.0 (d, J = 100 Hz), 131.9 (d, J = 12.4 Hz), 131.7 (d, J = 97.2 Hz), 131.5, 131.1 (d, J = 2.8 Hz), 130.7 (d, J = 9.9 Hz), 130.1 (d, J = 9.7 Hz, 2C), 129.1,


35


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128.5, 128.4, 128.2, 127.9 (d, J = 12.0 Hz, 2C), 127.5, 127.3, 126.9, 125.9, 125.8, 124.7, 21.3, 15.4 (d, J = 73.4 Hz). MS (EI HR) for C28H23OP [M+·]: calcd. 406.1486, found 406.1478. 39b (minor): white solid, mp 211‒212 oC.

31P


NMR (CDCl3, 300 MHz): δ 9.12 (d, J = 14.2 Hz, 1H), 8.17‒8.13 (m, 1H), 7.83‒7.63 (m, 3H), 7.65‒7.60 (m, 4H), 7.40‒7.01 (m, 8H), 1.40 (s, 3H), 1.32 (d, J = 13.6 Hz, 3H).

13C

NMR

(CDCl3, 75.5 MHz): δ 137.3 (d, J = 11.0 Hz), 136.0, 135.7 (d, J = 7.8 Hz), 135.1 (d, J = 2.6 Hz), 134.7 (d, J = 11.2 Hz), 134.0 (d, J = 91.3 Hz), 133.6, 132.0 (d, J = 12.1 Hz), 131.5, 131.5 (d, J = 97.3 Hz), 131.1 (d, J = 2.7 Hz), 130.9 (d, J = 9.9 Hz), 130.4 (d, J = 9.9 Hz, 2C), 129.1, 128.6, 128.5, 128.1, 128.0, 127.9, 127.8, 127.5, 126.9, 126.2 (d, J = 11.6 Hz, 2C), 125.0, 20.1, 15.9 (d, J = 73.8 Hz). MS (EI HR) for C28H24OP [M+·+ H]: calcd. 407.1559, found 407.1568. Crystal data for 39b: crystal system triclinic, space group P-1, unit cell dimensions a = 8.151(1) Å, b = 11.163(1) Å, c = 12.884(1) Å,  = 92.90(2)°, β = 108.43(2)°,  = 108.82(2)°; volume 1037.4(2) Å3, Z = 2, density (calcd) = 1.301 g/cm3, absorption coefficient 1.295 mm-1, F(000) = 428, θ range for data collection 3.67 to 77.34°; index ranges -10  h  8, -14  k  11, -14  l  15, reflections collected / independent 6641 / 4157. Goodness-of-fit on F2 = 1.157, final R indices [I>2(I)] R1 = 0.0694, wR2 = 0.2077,  max. /min. 0.45 / -0.69 e.Å-3. Acknowledgements The authors acknowledge the financial support from the Committee for Scientific Research, Poland (research project No. PBZ KBN 08/T09/98). Supporting information The copies of 1H, 13C and 31P NMR spectra of all compounds and X-ray crystallography data.

References a) Tang, W.; Zhang, X. New Chiral Phosphorus Ligands for Enantioselective Hydrogention Chem. Rev. 2003, 103, 3029, b) Lam, F.L.; Kwonk, F.Y.; Chan, A.S.C.; Top Organometal. Chem. Chiral Phosphorus Ligands with Interesting Properties and Practical Applications 2011, 36, 29; c) Liu, G.; Xu, G.; Luo, R.; Tang, W. Search for Ideal P-Chiral Phosphorus Ligands for Practical Asymmetric Hydrogention and Asymmetric Suzuki-Miyaura Coupling Synlett 2013, 24, 2465, d) Bigler, R.; Huber, R.; Mezzetti, A. Iron Chemistry Made Easy: Chiral N2P2 Ligands for Asymmetric Catalysis Synlett 2016, 27, 831. 1


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2 a)

Dang, T. P.; Kagan, H. B.; The asymmetric synthesis of hydratropic acid and amino-acids by homogeneous catalytic hydrogenation Chem. Comm. 1971, 481. b) Kagan, H. B.; Dang, T. P. J. Asymmetric catalytic reduction with transition metal complexes. I. Catalytic system of rhodium (I) with (-)-2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylophosphino)butane, a new chiral diphosphine J. Am. Chem. Soc. 1972, 94, 6429. 3 Fryzuk, M.B.; Bosnich, B. J. Asymmetric synthesis. Preparation of chiral methyl chiral lactic acid by catalytic asymmetric hydrogenation J. Am. Chem. Soc. 1979, 101, 3043. 4 Vineyard, B. D.; Knowles, W. S.; Sabacky, M. J.; Bachman, G. L.; Weinkauff, O. J. Asymmetric hydrogenation. Rhodium chiral bisphosphine catalyst J. Am. Chem. Soc. 1977, 99, 5946. 5 Knowles, W. S.; Sabacky, M. J.; Vineyard, B. D. Catalytic asymmetric hydrogenation Chem. Comm. 1972, 10. 6 Miyashita, A; Yasuda, A.; Takaya, H.; Toriumi, K.; Ito, T.; Souchi, T.; Noyori, R. Synthesis of 2,2’-bis(diphenylophosphino)-1,1’-binaphthyl (BINAP), an atropoisomeric chiral bis(triaryl)phosphine, and its use in the rhodium(I)-catalyzed asymmetric hydrogenation of alpha-(acylamino)acrylic acids J. Am. Chem. Soc. 1980, 102, 7932. 7 Hayashi, T. Chiral Monodentate Phosphine Ligand MOP for Transition-Metal-Catalyzed Asymmetric Reactions Acc. Chem. Res. 2000, 33, 354. 8 Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Genet, J-P.; Champion, N.; Dellis, P.; SYNPHOS, a new chiral diphosphine ligand: synthesis, molecular modeling and application in asymmetric hydrogenation Tetrahedron Letters, 2003, 44, 823. 9 Cereghetti, M.; Arnold, W.; Broger, E. A.; Rageot, A. (R)- and (S)-6,6’-dimethyl- and 6,6’dimethoxy-2,2’-diiodo-1,1’-biphenyls: Versatile intermediates for synthesis of atropoisomeric diphosphine ligands Tetrahedron Letters 1996, 37, 5347. 10 Kerrigan, N. J.; Dunne, E. C.; Cunningham, D.; McArdle P.; Gilligan, K.; Gilheany, D. G. Studies in the preparation of novel P-chirogenic binaphthyl monophosphanes (MOPs) Tetrahedron Letters 2003, 44, 8461. 11 Clarke E. F.; Rafter, E.; Muller-Bunz, H.; Higham, L. J.; Gilheany, D. G. The synthesis of P-stereogenic MOP analogues and their use in rhodium catalyzed asymmetric addition J. Organometallics Chem. 2011, 696, 3608 12 Hamada, T.; Buchwald, S. L. P-Chirogenic Binaphthyl-Substituted Monophospines: Synthesis and Use in Enolate Vinylation/Arylation Reactions Org. Lett. 2002, 4, 999. 13 Tang, W.; Qu, B.; Capacci, A. G.; Rodriguez, S.; Wei, X.; Haddad, N.; Narayanan, B.; Ma, S.; Grinberg, N.; Yee, N. K.; Krishnamurthy, D.; Senanayake, C. H. Novel, Tunable, and Efficient Chiral Bisdihydrobenzooxaphosphole Ligands for Asymmetric Hydrogenation Org. Lett. 2010, 12, 176. 14 Rodriguez, S.; Qu, B.; Fandrick, D. R.; Buono, N.; Haddad, N.; Xu, Y.; Herbage, M.A.; Zeng, X.; Ma, S.; Grinberg, N.; Lee, H.; Han, Z.S.; Yee, N.K.; Senanayake, C. H. AmineTunable Ruthenium Catalysts for Asymmetric Reduction of Ketones Adv. Synth. Catal. 2014, 356, 301. 15 Tang, W.; Capacci, A.G.; Wei, X.; Li, W.; White, A.; Nitinchandra, D.P.; Savoie, J.; Gao, J.J.; Rodriguez, S.; Qu, B.; Haddad, N.; Bruce, Z.; Lu, D.K.; Yee, N.K.; Senanayake, C. H. A General and Special Catalyst for Suzuki-Miyaura Coupling Proccesses Angew. Chem. Int. Ed., 2010, 49, 5879. 16 a) Qu, B.; Samankumara, L. P.; Savoie, J.; Fandrick, D. R.; Haddad, N.; Wei, X.; Ma, S.; Lee, H.; Rodriguez, S.; Busacca, C. A.; Yee, N. K.; Song, J. J.; Senanayake, C. H. Synthesis of Pyridyl-dihydrobenzooxaphosphole Ligands and Their Application in Asymmetric Hydrogenation of Unfunctionalized Alkenes J. Org. Chem. 2014, 79, 993.


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Page 38 of 39

17

a) Pietrusiewicz, K. M.; Zabłocka, M.; Monkiewicz, J. Optically active phosphine oxides. 2. Novel approach to enantiomeric dialkylphenylphosphine oxides J. Org. Chem. 1984, 49, 1522. b) Bodalski, R.; Koszuk, J.; Krawczyk, H.; Pietrusiewicz, K. M. An efficient synthesis of enantiomeric 17-phosphasteroid system J. Org. Chem. 1982, 47, 2219. c) Pietrusiewicz, K. M.; Wiśniewski, W.; Wieczorek, W.; Brandi, A. Optically active phosphine chalcogenides. 22. Stereochemistry and X-ray structure of the major endo cycloadduct of (S)methylphenylvinylphosphine oxide to cyclopentadiene Phosphorus, Sulfur, and Silicon 1995, 101, 253. d) Darling, S. D.; Brandes, S. J. Phosphinyl-substituted dienophiles: their synthesis and directive effects J. Org. Chem. 1982, 47, 1413. e) Maffei, M.; Buono G. The use of Lewis acids in the Diels-Alder reaction with organophosphorus dienophile compounds. Asymmetric approach with (Rp, Sp)-o-anisylphenylvinylphosphine oxide New. J. Chem., 1988, 12, 923. f) Qing-Qing, Z; Xin,Y.; You-Cai, X.; Lin, D.; Ying-Chun, C.; Aminocatalytic asymmetric Diels-Alder reaction of phosphorus dienophiles and 2,4-dienals Tetrahedron 2013, 69, 10369. 18 a) Choy, W.; Yang, H. Diels-Alder reactions of alpha-oxy-o-xylylenes J. Org. Chem. 1988, 53, 24, 5796. b) Charlton, J.L.; Alaudin, M.M.; Penner, G.H. Ortoquinodimethanes Tetrahedron, 1987, 64, 2873. c) Barluenga, J.; Garcia-Garcia, P.; Fernandez-Rodriguez, M.A.; Aguilar, E.; Merino, I. Lithium benzocyclobuteneoxide as a precursor of vinylogous enolate: Solvent-controlled synthesis of highly functionalized seven-membered benzocarbocycles Angew. Chem. Int. Ed., 2005, 44, 5875. d) Takinami, M.; Ukaji, Y.; Inomata, K. Enantioselective Diels-Alder reaction of o-quinodimethanes by utilizing tartaric acid ester as a chilar auxiliary Tetrahedron: Asymmetry, 2006, 17, 10, 1554. 19 a) Bubb, W. A.; Sternhell, S. Proton N.M.R. spectra of 1-substituted benzocyclobutenes (Bicyclo[4,2,0]octa-1,3,5-trienes) Austr. J. Chem. 1976, 29, 1685. b) Durr, H; Nickels, H.; Pacala, L. A.; Jones Jr. M. Benzocyclobutenylidene – cycloadditions, reactivity, and multiplicity J. Org. Chem. 1980, 45, 973 20 Berlin, K. D.; Butler, G. B. Poly(diphenylvinylphosphine oxide) J. Org. Chem. 1961, 26, 2537. 21 Korpiun, O.; Lewis, R. A.; Chickos, J.; Mislow, K. Synthesis and absolute configuration of optically active phosphine oxides and phosphinates J. Am. Chem. Soc. 1968, 4842. . 22 Pietrusiewicz K. M.; Zabłocka, M.; Wieczorek, W.; Brandi, A. Ground state conformation of (-)-S-methylphenylvinylphosphine oxide: A crystallographic and pcmodel inquiry Tetrahedron: Asymmetry 1991, 2, 6, 419. 23 Pietrusiewicz, K. M. Stereoselective synthesis and resolution of P-chiral phosphine chalcogenides Phosphorus, Sulfur and Silicon 1996, 109, 573. 24 a) Pietrusiewicz, K. M.; Kuźnikowski, M.; Koprowski, M. Synthesis of enantiomerically pure styryl and dienyl phosphine oxides via Pd-catalyzed Heck coupling reaction Tetrahedron: Asymmetry, 1993, 4, 10, 2143. 25 Jackman, L. M.; Sternhell, S. Applications of Nuclear Magnetic Resonance Spectroscopy in Organic Chemistry 2nd Edition, Pergamon Press, Oxford, 1972, 288. 26 a) Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry of Organic Compounds, John Willey & Sons Inc., Chichister, 1994. b) Wolf, C.; Dynamic Stereochemistry of Chiral Compounds; Royal Society of Chemistry, Cambridge, U.K., 2008. c) Flos, M.; Lameiras, P.; Denhez, C.; Mirand, C.; Berber, H. Atropoisomerism about aryl-(Csp3) bond: conformational behavior of substituted phenylcyclohexanes in solution J. Org. Chem, 2016, 81, 2372. d) Casarini, D.; Coluccini,C.; Lunazzi, L.; Mazzanti, A. Stereolabile and configurationally stable atropoisomers of hindered aryl carbinols J. Org. Chem. 2005, 70, 5098. e) Casarini, D.; Lunazzi, L.; Mazzanti, A. Conformational Studies by dynamic nuclear magnetic resonance.


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Page 39 of 39 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


59. Stereodynamics of conformational enantiomers in the atropoisomers of hindered naphthylcarbinols J. Org. Chem. 1997, 62, 3315. 27 a) Brooks, B., Bunton, C. A. Steric Effects in the hydrolysis of methyl- and tertbutylphenylphosphinic chloride and fluoride J. Org. Chem. 1975, 40, 2059. b) Wetzel, R.B.; Kenyon, G.L. J. Org. Chem. 1974, 40, 11, 1531. 28 Curran, D. P.; Kim, B. H.; Piyasena, H. P.; Loncharich, R. J.; Houk, K. N. Asymmetric induction in nitrile oxide cycloadditions to optically active acrylates. Comparisons of acrylate conformations in thermal and acid catalyzed 1,3-dipolar and Diels-Alder cycloaddition transition states J. Org. Chem., 1987, 52, 2137. 29 Pyne, S. G.; Griffith, R.; Edwards, M. Conjugate addition of amines to chiral (E) and (Z) vinyl sulfoxides, an enantioconvergent kinetic process Tetrahedron Letters, 1988, 29, 2089. 30 Brandi, A.; Cicchi, S.; Goti. A.; Pietrusiewicz, K. M.; Zabłocka, M.; Wiśniewski, W. Stereoselective Nitrone Additions to Vinyl Phosphine Derivatives. Effect of Phosphorus Substituents on Reaction Diastereoselectivity J. Org. Chem. 1991, 56, 4383. 31 Valderrama, J.A.; Gonzales, M.F.; Valderrama, C. Studies on quinones. Part 32. Regioselective synthesis of benz[b]phenantridines related to phenantroviridone Tetrahedron 1999, 55, 20, 6039. 32 Harvey, R. G.; Pataki, J.; Cortez, C.; Di Raddo, P.; Xi Yang, Ch. A new general synthesis of polycyclic aromatic compounds based on enamine chemistry J. Org. Chem. 1991, 56, 1210. 33 Krause, E.; Pohland, R. Dicyclohexyl-zinn, hexacyclohexyl-distannan und andere cyclohexyl-zinnverbindungen Chem. Ber. 1924, 54, 532. 34 Becker, D.; Nagler, M.; Sahali, Y.; Haddad, N. Regiochemistry and stereochemistry of intramolecular [2 + 2] photocycloaddition of carbon-carbon double bonds to cyclohexenones J. Org. Chem. 1991, 56, 14, 4537. 35 Di Deo, M.; Marcantoni, E.; Torregiani, E. A simple, efficient, and general method for the conversion of alcohols into alkyl iodides by CeCl3*7H2O/NaI system in acetonitrile J. Org. Chem. 2000, 65, 9, 2830. 36 Sheldrick G. M. A short history of SHELX Acta Cryst. 2008, A64, 112.


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