Modular P-Chirogenic Phosphine-Sulfide Ligands: Clear Evidence for Both Electronic Effect and P-Chirality Driving Enantioselectivity in Palladium-Catalyzed Allylations

Article

pubs.acs.org/Organometallics

Modular P‑Chirogenic Phosphine-Sulﬁde Ligands: Clear Evidence for

Both Electronic Eﬀect and P‑Chirality Driving Enantioselectivity in

Palladium-Catalyzed Allylations

Jerome Bayardon,*^,†Milene Maronnat,^†Adam Langlois,^‡Yoann Rousselin,^†Pierre D. Harvey,^‡

́

̂

̀

and Sylvain Juge*^,†

́

^†Institut de Chimie Molec

Savary, BP 47870, 21078 Dijon Cedex, France

^‡Dep

́

ulaire de l’Universite

́

de Bourgogne-Franche-Comte

́

(ICMUB-Ster

́ ́

eochIM UMR 6302), 9 Avenue A.

́

artement de Chimie, Universite de Sherbrooke, Sherbrooke, Queb

́

ec, Canada J1K2R1

S

* Supporting Information

ABSTRACT: Using the ephedrine methodology, modular stereo-

selective syntheses of a new class of P-chirogenic phosphines

bearing a sulfur-chelating arm (P*,S-hybrid ligand) are described.

A ﬁrst series of syntheses based on a Fries-like rearrangement of P-

chirogenic phosphinite-boranes, which are prepared from 2-

bromobenzyl or 2-bromophenethyl alcohol and are mediated by

metal−halide exchange, have been performed. This rearrangement

aﬀords phosphine-boranes stereospeciﬁcally with an o-hydroxy-

alkylphenyl substituent. The latter residue is subsequently converted into a sulfur-containing group. In a second series, the

stereoselective syntheses were achieved according to a new strategy involving a reaction of a thiophenyllithium reagent with a P-

chirogenic phosphinite. The X-ray structures of the P*,S ligands and their palladium complexes allow us to address the absolute

conﬁguration at both the phosphorus and sulfur centers. The P*,S ligands were used in palladium-catalyzed allylic alkylations, as

tests, aﬀording asymmetric inductions up to 96% ee. Computer modeling corroborates the regio- and enantioselectivity of the

Pd-catalyzed allylations and the low inﬂuence of the substituent carried by the sulfur moiety, particularly when the chelate forms

a six-membered ring with the metal.

cases, the chirality in these P,S ligands is located on the carbon-

based backbone, producing a planar or an axial chirality (see

examples 1−5 in Chart 1).¹³In contrast, very few examples of

P-chirogenic phosphine-sulﬁde chelates such as 6 have been

described to date, despite the fact that promising anticancer

activities of P*,S-gold(I) complexes and excellent asymmetric

induction in catalysis were reported.¹⁴

INTRODUCTION

■

Nowadays, metal-catalyzed asymmetric reactions are powerful

methods for the production of enantiomerically enriched

compounds.¹Even though a lot of chiral phosphorus ligands

have been reported,²the design and synthesis of new types of

compounds with improved catalytic performance continue to

attract the interest of synthetic chemists.³This interest is

readily augmented by the relevance of chiral phosphorus

compounds in biology,⁴health,⁵agrochemistry,⁶coordinating

polymers,⁷luminescent materials,⁸stereoselective synthesis,⁹

and organocatalysis.¹⁰Usually, highly enantioselective catalyzed

reactions are observed with diphosphorus ligands, but

heteronuclear chelates containing a phosphorus atom have

also demonstrated their eﬃciency.^2,11For example, numerous

chiral P,N ligands have been reported to be eﬀective in a range

of catalyzed asymmetric allylic alkylation, hydrosilylation,

hydroboration, or Heck reactions.^2eOn the other hand,

phosphorus compounds containing a sulfur moiety (P,S

ligands) have also attracted much attention because its

coordination onto the metal induces chirality at the S-center,

resulting in an asymmetry placed closed to the catalytic

site.¹²⁻¹⁴For the rather rare literature examples, the use of

chiral P,S-bidentate ligands in asymmetric catalysis ﬁnds

applications in the challenging enantioselective Mannich,

cycloaddition, and Pauson−Khand reactions.^12,13For these

Recently, the stereoselective synthesis of P-chirogenic

organophosphorus compounds has made signiﬁcant progress

Chart 1. Selected Examples of Chiral P,S Ligands

Received: July 9, 2015

A

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Scheme 1. Synthesis of P-Chirogenic Phosphine-Sulﬁdes 13a−p from Phosphinite-Boranes 9a−f

Table 1. Preparation of o-Functionalized Phosphine-Boranes 10a−f and 11a−j by o-Fries-like Rearrangement of P-Chirogenic

Phosphinite-Boranes 9a−f

R¹PhP(BH₃)O(CH₂)_n-o-BrPh

R¹PhP(BH₃)o-Ph(CH₂)_nOH

R¹PhP(BH₃)o-Ph(CH₂)_nX

a

b

a

b

c

a

b

entry

R¹

n

9

yield (%)

10

yield (%)

method

11

X

yield (%)

1

o-An

o-Tol

o-biPh

Fc

1

2

9a

9b

9c

9d

9e

9f

71

74

63

51

74

73

10a

10b

10c

10d

10e

10f

62

80

−

58

80

70

A

B

C

A

B

C

A

B

C

A

B

C

A

11a

11g

11b

11h

11c

11d

11i

OMs

Br

77

67

65

68

58

47

2

3

Br

4

OMs

Br

5

6

Br

e

7

OMs

Br

34

d

8

78

75

78

83

72

70

85

9

Fc

10

11

12

13

14

Fc

11i

Br

m-Xyl

o-An

11e

11j

OMs

Br

11j

Br

11f

OMs

a

b

c

d

e

ee > 99%. Isolated yield. Method A: MsCl/NEt₃; B: PPh₃/CBr₄; C: mesylate 11/NaBr. ee > 99% after recrystallization. Overall yield from 9c.

Figure 1. OLEX2²⁰view of P-chirogenic phosphine-sulﬁdes 13g,h showing thermal ellipsoids at the 50% probability level. The disordered moiety

was omitted for clarity. Selected bond lengths (Å), angles (deg), and dihedral angles (deg) for 13g/13h, respectively: P1−C7 1.831(2)/1.834(2);

P1−C15 1.841(2)/1.838(2); C7−P1−C15 101.84(10)/100.59(10); C8−P1−C7 101.65(10)/101.93(10); C7−P1−C15−C16 162.29(18)/

147.93(19); C8−P1−C15−C16 92.78(19)/106.92(19).

thanks to the development of new eﬃcient methods using the

borane as protecting group and asymmetric inductors such as

menthol, amines, or amino alcohols.¹⁵In the context of

growing interest in functionalized chiral organophosphorus

compounds, we described powerful stereoselective syntheses of

o-hydroxyaryl-,^16bo-(hydroxyalkyl)aryl-, and more recently o-

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boronatophenylphosphines.¹⁷We now report eﬃcient syn-

theses of P-chirogenic phosphine-sulﬁdes with phenyl and

phenylalkyl bridges and their testing as P*,S ligands in

palladium-catalyzed asymmetric allylic substitutions.

Table 2. Preparation of Phosphine-Sulﬁdes 13 and Their

Borane Complexes 12

starting

product

R¹PhP-o-

Ph(CH₂)_nSR

R¹PhP(BH₃)o-Ph(CH₂)_nSR

yield

b

yield

b

a

RESULTS AND DISCUSSION

entry

1

11

R¹

n

R

12

(%)

13

(%)

■

11a or

11g

o-An

1

Ph

12a

56

13a

84

The stereoselective synthesis of P-chirogenic phosphine-sulﬁdes

13a−p with a phenylalkyl bridge was based on stereoselective

ortho Fries-like rearrangement of phosphinite-boranes 9a−f to

aﬀord the corresponding o-hydroxalkylphosphine-boranes

10a−f, which were transformed in sulﬁde derivatives by

subsequent reactions as illustrated in Scheme 1.

2

3

4

5

11h

11c

11d

o-Tol

o-biPh

Fc

1

Ph

12b

12c

12d

12e

54

13b

13c

13d

13e

93

c

d

−

74

84

91

83

11e or

11j

m-Xyl

78

First, the P-chirogenic phosphinite-boranes 9a−f were

stereoselectively prepared in 51−74% yields by reaction of

the chlorophosphine-boranes 7a−e (obtained using the

ephedrine methodology)¹⁸with the 2-bromobenzyl or 2-

bromophenethyl alcohols 8a,b (Scheme 1, Table 1). The

synthesis of the o-(hydroxyalkyl)phenylphosphine-boranes

10a−f was then achieved by intramolecular ortho Fries-like

rearrangement of the corresponding phosphinite-boranes 9a−f,

mediated by metal−halide exchange with t-BuLi at −78 °C

(Scheme 1, Table 1). The rearrangement proceeds with

complete retention of the conﬁguration at the P-center,

which is conﬁrmed by X-ray structure determination of the

phosphine-sulﬁdes 13g,h (Figure 1). It leads to the o-

(hydroxyalkyl)phenylphosphine-boranes 10a−f in 58−80%

yields (Table 1). The reaction of compounds 10a−f with

methanesulfonyl chloride or with a triphenylphosphine/carbon

tetrabromide mixture aﬀorded the corresponding mesylate

derivatives 11a−f (or bromides 11g−j) with yields up to 85%

(Table 1). Alternatively, the bromide derivatives 11g−j can also

be obtained in 47−78% yields by the substitution of the

mesylates with sodium bromide (Table 1, method C; entries 3,

6, 10, 13).

The reaction of mesylates or bromide derivatives 11a−j with

lithium thiolates, prepared from the deprotonation of thiols

such as thiophenol, ethyl, benzyl, or tert-butyl mercaptans, etc.,

by n-BuLi, aﬀorded the corresponding P-chirogenic phosphine-

sulﬁdes as borane complexes 12a−p in 32−84% yields (Table

2). Interestingly, the o-biphenylphosphine-sulﬁdes 13c and 13p

were synthesized from the mesylate 11c in 74% and 63%

overall yields, respectively, without puriﬁcation of the

intermediates 12c and 12p, which are partially decomplexed

(entries 3, 16).

6

11f

11a

o-An

2

1

Ph

Et

12f

12g

12h

12i

12j

32

70

73

58

63

13f

13g

13h

13i

13j

88

90

83

7

8

t-Bu

Bn

9

10

11a or

11g

p-An

c

d

11

12

11a

o-An

1

o-An

12k

12l

−

13k

13l

58

3,5-

Me₂Ph

45

86

c

d

13

11a

o-An

1

2,6-

Me₂Ph

12m

−

13m

58

14

15

16

11a

11c

o-An

1

4-CF₃Ph 12n

56

42

13n

13o

13p

84

o-An

(i-Pr)₃Si

12o

12p

84

c

d

o-biPh

2,6-

Me₂Ph

c

−

63

a

b

d

ee > 99%. Isolated yield. Not isolated. Overall yield from

mesylates 11.

The structure of the phosphines 13g,h shows that the

phenylmethylene sulﬁde substituent is in a staggered

conformation with respect to the sulfur atom facing the lone

pair of the phosphorus atom (Figure 1). In addition, both

structures show the methylene sulﬁde substituent in anti

position of the phosphorus−anisyl bond, probably to minimize

steric hindrance, with C7−P1−C15−C16 dihedral angles of

162.29(18)° and 147.93(19)°, respectively (Figure 1).

In order to compare the inﬂuence of the sulﬁde arm length of

the homochiral ligands such as in 13a,h (n = 1) and 13f (n = 2)

in asymmetric catalysis, the P-chirogenic o-phenylthio- and o-

(tert-butylthio)phenylphosphines 13q,r without methylene

spacers (n = 0) were prepared from the o-bromophenyl-

thioethers 16a,b (Scheme 2). The phenylene-bridged phos-

Scheme 2. Stereoselective Synthesis of P-Chirogenic

Phosphine-Sulﬁdes 13q,r

The decomplexation of the borane complexes 12a−p was

performed using DABCO at room temperature, to aﬀord

stereospeciﬁcally the corresponding free phosphine-sulﬁdes

13a−p in 58−91% isolated yields (Table 2). Noteworthy, the

enantiomeric excesses of the P-chirogenic phosphine-sulﬁdes

13a−p (>99%), as well as those of their precursors 9a−f−12a−

p were checked by HPLC analysis on a chiral column by

comparison with racemic samples.

Recrystallizations of the free phosphine-sulﬁdes 13g,h in a

dichloromethane/methanol mixture gave crystals suitable for X-

ray analysis (Figure 1). Both compounds crystallize in the non-

centrosymmetric P2₁group, and the Flack¹⁹parameter

reﬁnement allows the unambiguous determination of the S-

absolute conﬁguration at the phosphorus atom. This

conﬁguration is in good agreement with a stereochemistry

resulting from a retention of conﬁguration during the Fries-like

rearrangement¹⁶of the phosphinite 9a and in the subsequent

reactions leading to the free phosphine-sulﬁdes 13g,h.

phine-sulﬁdes 13q,r were synthesized in 39% and 56% yield,

respectively, by a stereoselective reaction of the P-chirogenic

phosphinite 15 with the corresponding lithium reagent,

previously obtained from a metal−halide exchange of the (2-

bromophenyl)sulﬁde 16a,b (Scheme 2). On the other hand,

the P-chirogenic phosphinite 15 was stereoselectively prepared

by a decomplexation of the borane complex 14 synthesized

according to the ephedrine methodology (Scheme 2).^15b,18,21

C

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a b

,

Table 3. Asymmetric Allylation of Dimethylmalonate Using P*S-Ligand-Palladium Complexes

phosphine-sulﬁde 13

product 20

product 21

product 22

c

d

c

d

c

d

entry

R¹

n

R

abs conf

ee (%)

abs conf

ee (%)

56

abs conf

ee (%)

24

1

2

3

13a

13b

13c

13d

13e

13f

o-An

o-Tol

o-biPh

Fc

1

2

1

0

Ph

Et

(S)

(R)

(S)

94

71

96

50

30

86

92

90

94

96

95

96

95

93

95

16

85

(S)

(R)

(S)

(R)

27

3

(S)

(R)

34

6

e

4

5

m-Xyl

o-An

o-biPh

o-An

6

7

13g

13h

13i

(S)

41

11

34

54

44

66

53

(R)

30

24

25

21

20

13

8

t-Bu

Bn

9

10

11

12

13

14

15

16

17

13j

p-An

13k

13l

o-An

3,5-Me₂Ph

2,6-Me₂Ph

4-CF₃Ph

2,6-Me₂Ph

Ph

13m

13n

13p

13q

13r

t-Bu

a

b

Reactions were carried out in dichloromethane or toluene (0.125 M) in substrate and proceeded to completion. Allylated malonates obtained with

yields >90%. Determined by comparison of speciﬁc rotation with literature values.²²Determined by HPLC on a chiral column. Reaction time 16

c

d

e

h.

The enantiomeric purities of the phosphine-sulﬁdes 13q,r were

checked by HPLC on a chiral column, and no racemization was

detected during their synthesis (ee >99%).

The X-ray structure of the phosphine 13q complexed to

palladium (vide infra Figure 3) allowed the determination of

the S-absolute conﬁguration at the phosphorus atom, which is

in good agreement with the substitution of the P-chirogenic

phosphinite 15 with an inversion of conﬁguration at the P-

center.

Palladium-Catalyzed Asymmetric Allylations. The P-

chirogenic phosphine-sulﬁdes 13 were used as ligands in the

palladium-catalyzed allylic reactions of malonate, benzyl-amine,

and alcohol.

First, the allylation of dimethyl malonate was performed with

the allylic substrates 17−19 in dichloromethane or toluene,

using 2 mol % of [Pd(C₃H₅)Cl]₂and 4 mol % of phosphine-

sulﬁdes 13, N,O-bis(trimethylsilyl)acetamide (BSA), and a

catalytic amount of potassium acetate as base (Table 3). The

reactions were usually completed within 1 h at room

temperature to selectively aﬀord the mono-allylated malonates

20−22. The results are reported in Table 3.

led to the R-alkylated product 20 with moderate enantiomeric

excesses of 50% and 30%, respectively (entries 4, 5).

Surprisingly, changing the phenyl substituent of the sulfur

atom in the o-anisylphosphine-sulﬁde 13a by alkyl or aryl

groups such as ethyl, tert-butyl, benzyl, p- or o-anisyl, 3,5-

dimethyl- or 2,6-dimethylphenyl, or p-triﬂuoromethylphenyl,

i.e., P*,S ligands 13g−n, led to similar asymmetric inductions.

Thus, in these cases the allylated product (S)-20 was obtained

with enantiomeric excesses ranging from 90% to 96% ee (vs

94% ee for 13a, entries 1 and 7−14). In addition, changing the

phenylsulﬁde group of the o-biphenyl ligand 13c by a more

bulky 2,6-dimethylphenylsulﬁde moiety, as in case of

phosphine-sulﬁde 13p, gave similar asymmetric inductions

(95% vs 96% ee, entries 3, 15). Moreover, when the

phenylmethylene bridge between the phosphine and sulﬁde

moieties of 13a was changed by phenethyl or phenylene (see

13f,q), the asymmetric catalysis aﬀorded the allylated product

(S)-20 with lower enantioselectivites of 86% and 16%,

respectively, vs 94% ee (entries 1, 6, 16). In the case of the

phosphine-sulﬁde 13h, bearing a tert-butyl group on the sulfur

moiety, changing the phenylmethylene bridge by phenylene led

to the S-product 20 with a small decrease of enantioselectivity

(85% vs 90% ee; entries 8, 17).

When the catalysis was performed with the phosphine-

phenylsulﬁdes 13a−c bearing an o-anisyl, o-tolyl, or o-biphenyl

substituent on the phosphorus moiety, the allylated product 20

was obtained in S-absolute conﬁguration with enantiomeric

excesses up to 96% (Table 3, entries 1−3). In contrast, the use

of ferrocenyl or m-xylylphosphine-phenylsulﬁdes 13d (or 13e)

On the other hand, the asymmetric palladium-allylation of

dimethyl malonate in the presence of phosphine-sulﬁdes 13 was

also investigated with the allylic subtrates 18 and 19 in toluene

or dichloromethane, respectively. Both allylations, which were

D

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complete in 1 h at room temperature, aﬀorded lower

enantioselectivities than that for substrate 17. However, in

this case, the enantioselectivity was also strongly dependent

upon the substituents on the phosphorus atom and signiﬁcantly

less dependent upon those on the sulﬁde moiety. Thus, when

the catalysis was performed with ligands 13a,c,e (i.e., bearing an

o-anisyl, o-biphenyl, or m-xylyl substituent on the phosphorus

atom), the allylated products 21 and 22 were obtained with

enantiomeric excesses ranging from 56% (S) to 24% (R) (Table

3, entries 1, 3, 5). In contrast, changing the phenyl substituent

of the sulfur atom on ligand 13a by an ethyl, tert-butyl, benzyl,

p- or o-anisyl, or 3,5-dimethyl- or 2,6-dimethylphenyl group led

to very similar asymmetric inductions. Indeed, the allylated

products 21 and 22 were obtained with enantiomeric excesses

up to 66% and 30%, respectively (entries 7−13).

xylyl substituent on the P-center) led to the (S)- or (R)-N-

benzyl product 23 with enantiomeric excesses ranging from

37% to 89% (entries 1−5). Again, the inﬂuence of the

substituents of the S atom in ligands 13a−e was much less

important, because changing phenyl by various alkyl or aryl

groups led to the allylated product (S)-23 with enantiomeric

excesses in the range 47−87% (entries 6−13). The use of o-

biphenylphosphine-sulﬁde ligands 13c and 13p, bearing a

phenyl or a 2,6-dimethylphenyl substituent on the sulﬁde arm,

provided similar results. Indeed, the catalyzed allylation of

benzyl amine led to product (S)-23 with 89% ee (entries 3, 14).

On the other hand, the use of phosphine-sulﬁde 13j or 13p in

Pd-catalyzed allylic substitution of benzyl alcohol with the (E)-

1,3-diphenylprop-2-en-1-yl acetate 17 led to the allyl benzyl

ether (R)-24 with 83% and 87% ee, respectively, in 2 h (entries

9, 14).

Finally, all these results illustrate the importance of the

substituents on the P atom and signiﬁcantly less on the sulﬁde

moiety. This is notably the case for the phenylmethylene-

bridged ligands 13 (n = 1), giving a six-membered chelate with

the palladium (Tables 3, 4). By contrast, the behavior of the

phenylsulﬁde ligands 13 with a phenylene bridge (n = 0) (i.e.,

forming ﬁve-membered rings by chelatation with the metal) in

asymmetric catalyzed allylation was completely diﬀerent. Thus,

the substituent at the S-center appears crucial.

Finally, the allylic substitution of (E)-1,3-diphenylprop-2-en-

1-yl acetate 17 catalyzed by the palladium complexes with the

phenylmethylene-bridged P*,S ligands 13 (n = 1) was

investigated using benzylamine and benzyl alcohol as

nucleophiles (Table 4). The reactions were performed at

Table 4. Asymmetric Allylation of Benzylamine and Benzyl

Alcohol Using Pd Complexes with the Phenyl-Methylene-

a b

,

Bridged P*S Ligand 13

From a mechanistic standpoint, this series of P-chirogenic

phosphine-sulﬁde ligands 13a−p is usefull for the under-

standing of the enantioselectivity of their derivatives, by

comparing the eﬀect of the structural modiﬁcation of the

ligand at the P- or S-center on the catalytic properties. In this

aim, X-ray structures, variable-temperature ³¹P NMR experi-

ments, and computational calculations were performed for the

palladium complexes 25−28 with the P-chirogenic o-

anisylphosphine-sulﬁde P*,S ligands 13a (n = 1), 13f (n =

2), 13q, and 13r (n = 0).

First, crystals of the P*,S-palladium complexes 25 and 26

were obtained by mixing ligands 13a,q with PdCl₂(CH₃CN)₂,

respectively,^13cand their structures were established by X-ray

crystallography (see OLEX views in Figures 2 and 3,

respectively).

phosphine-sulﬁde 13

product 23

product 24

abs

conf

ee

(%)

abs

conf

ee

d

c

d

c

entry

R¹

R

(%)

1

13a

13b

13c

13d

13e

13g

13h

13i

o-An

Ph

(R)

(S)

(R)

77

54

89

49

37

70

47

67

85

83

82

86

87

89

2

o-Tol

3

o-biPh Ph

Fc Ph

m-Xyl Ph

4

5

6

o-An

Et

7

t-Bu

Bn

8

9

13j

p-An

(R)

83

87

10

11

12

13

14

13k

13l

o-An

3,5-Me₂Ph

2,6-Me₂Ph

4-CF₃Ph

13m

13n

13p

o-biPh 2,6-Me₂Ph

a

Reactions were carried out in dichloromethane for benzylamine and

b

in toluene for benzyl alcohol. Isolated yields were superior to 90%.

c

Determined by comparison of the speciﬁc rotation with literature

values.^22,23Determined by HPLC on a chiral column.

d

room temperature in dichloromethane or toluene, using TBAF

or Cs₂CO₃as additive or base, respectively, to aﬀord the

corresponding allylated products 23 and 24 in 2−4 h. The

results are summarized in Table 4.

As previously observed for the allylic substitution of

dimethylmalonate with (E)-1,3-diphenylprop-2-en-1-yl acetate,

17 (Table 3), the enantioselectivities for the palladium-

catalyzed allylation of benzylamine showed a strong depend-

ence on the ligand substituents of the phosphine unit (Table 4,

entries 1−5). Thus, the phosphine-phenylsulﬁde ligands 13a−e

(i.e., bearing an o-anisyl, o-tolyl, o-biphenyl, ferrocenyl, or m-

Figure 2. OLEX2²⁰view of palladium complex 25 (Pd(13a)Cl₂)

showing thermal ellipsoids at the 50% probability level. Solvent was

omitted for clarity. Selected bond lengths (Å), angles (deg), and

dihedral angles (deg): Pd1−P1 2.2413(14); Pd1−S1 2.2806(14);

Pd1−Cl1 2.3026(15); Pd1−Cl2 2.3664(15); P1−Pd1−S1 94.18(5);

P1−Pd1−Cl1; 87.39(5); C21−S1−Pd1 112.0(2); C21−S1−C20

98.0(3); C16−C20−S1 112.2(2); Cl7−C16−C20−S1 110.9(5);

C14−C15−P1−C7 −1.3(5); C14−C15−P1−C8 110.3(5).

E

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Figure 3. OLEX2²⁰view of disordered palladium complex 26 (Pd(13q)Cl₂) showing thermal ellipsoids at the 50% probability level. The asymmetric

unit is composed of two disordered molecules; distances reported are the mean distances (see Supporting Information). For clarity, major and minor

disordered segments are depicted on the left and right, respectively. The solvent molecule was omitted for clarity. Selected mean bond lengths (Å),

angles (deg), and dihedral angles (deg): Pd1−P1 2.243(2); Pd1−S1 2.266(3); Pd1−Cl1 2.288(3); Pd1−Cl2 2.372(2); P1−Pd1−S1 88.03(10);

C15−C16−S1−C20 −123.0(6); C14−C15−P1−C7 −44.3(7); C14−C15−P1−C8 68.8(7); C15−C16−S2B−C31 −136.9(9); C16−C15−P1−Pd

2.0(6).

Table 5. ³¹P NMR Data of Dichloropalladium(II) Complexes with P*S Ligands 13

a

phosphine-sulﬁde 13

Pd(13)Cl₂, ³¹P NMR δ (ppm)

+25 °C

entry

n

R

−80 °C

+19.5

1

2

3

4

13a

13f

13q

13r

1

2

0

Ph

25

27

26

28

+19.3

+17.6

+50.4

+46.3

Ph

+18.2

b

Ph

+51.6, +50.9

+47.2

t-Bu

a

b

³¹P NMR analysis in CD₂Cl₂. 1:2 ratio

Both X-ray structures of the dichloropalladium complexes 25

square planar. While the Pd1−P1 and Pd1−S1 bond lengths

about the Pd(II)-center are similar in both structures, the

angles show slight diﬀerences due to the formation of the six-

and ﬁve-membered rings, respectively, i.e. P1−Pd−S1

94.15(5)° vs 88.03(10)° for 19 and 20 (Figures 2 and 3).

Conversely, in both complexes 25 and 26 the Pd−Cl bonds

lengths are longer in the anti position of the phosphorus than

of the sulfur atom, i.e., 2.3664(15)°, 2.372(2)° vs 2.3026(15)°,

2.288(3)°. Computational calculations on π-allylpalladium

complex 29a (i.e., ligand 13a; see Supporting Information)

and similar reported results^13,22support the regioselectivity of

the nucleophilic attack on the complexed π-allyl moiety in the

anti position of the phosphorus atom due to a smaller Pd−C(3)

bond strength.

and 26 show the ligands 13a,q bonded to the Pd(II) metal

center with their phosphorus and sulfur atoms forming a six- or

ﬁve-membered ring, respectively (Figures 2, 3). The X-ray

structure of 25 (i.e., Pd(13a)Cl₂) shows only one diastereo-

isomer within the crystal lattice, with the o-anisylphosphine and

phenylsulﬁde bonds respectively placed in equatorial and axial

positions of the boat conformation, with dihedral angles C14−

C15−P1−C7 and C14−C15−P1−C8 of −1.3° and 110°

values, respectively. By contrast, complex 26 (i.e., Pd(13q)Cl₂)

exists as two epimers (depending on the position of the phenyl

substituent on the sulfur atom) in the unit cell in an 8:2 ratio

(Figure 3). Both epimers exhibit a relatively ﬂat ﬁve-membered

ring associated with the rigidity of the phenylene unit

occupying one side of the chelate ring opposite the metal

(Figure 3, C16−C15−P1−Pd 2.0°). Moreover, the major

epimer shows the phenyl sulﬁde moiety in trans position with

respect to the o-anisyl substituent, whereas the structure for the

minor species is cis (Figure 3). In both palladium complexes 25

and 26, the two remaining chlorides around the Pd(II) atom

are unavoidably in the cis position (predicted for chelate

species). Changing the phenylmethylene bridge of the

complexed ligand by phenylene (i.e., 13a in 25 vs 13q in 26)

does not aﬀect the metal coordination scheme, which remains

On the other hand, the ³¹P NMR data of dichloropalladium-

(II) complexes 25−28 prepared from the P-chirogenic P*,S

ligands 13a, 13f, 13q, and 13r were obtained using dichloro-

methane at both 25 and −80 °C. The ³¹P NMR chemical shifts

(from +17.6 to +50.4 ppm), which are reported in Table 5, are

consistent with the values reported in the literature for similar

palladium P,S-chelates.^13c,24

The ³¹P NMR spectrum of palladium(II) complex 26

exhibits two signals in a 1:2 ratio at −80 °C, whereas only

one signal is observed at 25 °C (Table 5, entry 2). This result is

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consistent with a facile isomerization of the complex at the

sulfur atom, especially as both epimers were observed in the

crystal structure of complex 26 (Figure 3).²⁵The ³¹P NMR

behavior of complexe 26, which shows a coalescence

temperature T_cof 285 K and a peak separation Δν_{178 K}of

140 Hz, corresponds to an energy barrier of ΔG^#= 5.6 0.1 kJ

mol⁻¹, which is in good agreement with the computational

calculations aﬀording 7.2 kJ mol⁻¹for the epimerization (see

Supporting Information). Besides, the ³¹P NMR spectra of

complexes 25, 27, and 28 showed only one signal at 25 and

−80 °C (Table 5, entries 1, 3, and 4). In spite of this

observation, epimerization is most likely occurring for these

complexes, as the calculated energy diﬀerence between both

epimers of 25a and 25b is still signiﬁcantly smaller than that

computed for 26 (i.e., 0.5 vs 7.2 kJ mol⁻¹; see Supporting

Information).

In addition to the regioselectivity of the nucleophilic attack

on the complexed π-allyl moiety, which is oriented in anti

position of the phosphorus atom (vide supra), the asymmetric

induction clearly depends on the P-chirogenic center and the

nature of the ligand bridge. Thus, the regioselectivity of the

asymmetric palladium-catalyzed allylations with the phenyl-

methylene (or phenethylene)-bridged P*,S ligand 13a (or 13f)

is clearly directed by the P-chirogenic center, whereas the

nature of the substituent on the sulfur atom has much less

inﬂuence. Conversely for the phenylene-bridged P*,S ligands

13q and 13r, as their complexation aﬀords a quasi-ﬂat ﬁve-

membered ring (again due to the presence of the aryl

component on the chelate), the aryl substituents on the P

atom are placed in similar relative orientations (i.e., no axial and

equatorial positions) on both sides of the plane. Consequently,

this structural feature induces no additional chirality at the

palladium center (Figure 3). In the latter case, based on the

nature of the substituent on the sulfur atom (i.e., t-Bu or Ph),

the Pd complex epimeric ratio must strongly change, leading to

signiﬁcantly more inﬂuence on the asymmetric induction (85%

vs 16% ee; Table 3, entries 16, 17).

Finally, we performed computer modeling of the π-

allylpalladium complex derived from the P-chirogenic phos-

phine-sulﬁde ligands 13a and 13q, in order to provide an

explanation for the enantioselectivity of the catalyzed allylation

reactions (Figure 4 and Supporting Information). The relative

energies of π-allylpalladium-(P*,S-13a) complexes 29 derived

from the (E)-1,3-diphenylprop-2-en-1-yl acetate 17 are

representative examples (Figure 4).

The possible stereoisomers of the π-allylpalladium complexes

29 were computed, taking into account the boat conformation

of the six-membered ring and the S-absolute conﬁguration at

the P-center (see Supporting Information). Thus, the stereo-

isomers with the o-anisyl substituent in equatorial and axial

positions and with both conﬁgurations of the sulﬁde moiety, as

well as those with the complexed π-allyl moiety in M- and W-

shapes or dissymmetric conformations, were computed. Among

the numerous computed stereoisomers only complexes 29a−c

exhibit the lowest calculated total energies (Figure 4).

Interestingly, the conﬁguration of the sulﬁde moiety, i.e.,

phenyl in equatorial or axial position, has little inﬂuence on the

total calculated energy, as the diﬀerence is only 0.5 kJ mol⁻¹

between epimers 29a and 29b (Figure 4). Nucleophilic attack

at the 3-position of the π-allylic system of stereoisomer 29a or

29b is fully consistent with the observed enantioselectivity of

the products (S)-20 and (R)-23 (Figure 4; Table 3, 4 entries

1). When the nucleophilic attack occurs at the 3-position of the

Figure 4. Computer modeling of the stereochemical course in Pd-

catalyzed allylation using the P-chirogenic phosphine-sulﬁdes 13a.

π-allyl complex 29c, the products are obtained with the

opposite absolute conﬁgurations, i.e., (R)-20 and (S)-23

(Figure 4). However, as the calculated energy of the

stereoisomer 29c is 6.0 kJ mol⁻¹higher than 29a, this

stereochemical pathway is defavored (Figure 4). However, it

is suspected that such a stereochemical pathway becomes

favored by changing the o-anisyl group in ligand 13a by a

bulkier substituent such as ferrocenyl or m-xylyl, which could

explain the formation of the allylated products 20−23

systematically with opposite conﬁguration, using ligand 13d,e

(Tables 3, 4, entries 4, 6).

CONCLUSION

■

The stereoselective syntheses of a new class of P-chirogenic

phosphines bearing a sulﬁde chelating arm (P*,S ligand),

allowing an easy design of their organophosphorus and sulfur

moieties, are described using P-electrophilic building blocks

prepared from the ephedrine methodology. A ﬁrst synthesis is

based on a Fries-like rearrangement of P-chirogenic phosphinite

boranes, which are prepared from 2-bromobenzyl- or 2-

bromophenethyl alcohol, mediated by metal−halide exchange.

The rearrangement aﬀords stereospeciﬁcally the phosphine-

boranes with an o-hydroxyalkylphenyl substituent, which is

transformed at the sulﬁde group by subsequent substitutions.

The second method of synthesis is based on a new strategy

involving reaction of a thiophenylithium reagent with a P-

chirogenic phosphinite. The X-ray structures of the hybrid P*,S

ligands and palladium complexes allow attributing the absolute

conﬁguration at both the phosphorus and sulfur center, the

chirality of which is induced by complexation. The P*,S hybrid

ligands were used in palladium-catalyzed allylic alkylations,

aﬀording asymmetric inductions up to 96% ee. Computer

modeling corroborates the regio- and enantioselectivity of the

Pd-catalyzed allylations and the low inﬂuence of the

substituents borne by the sulﬁde moiety particularly when the

chelate with the metal forms a six-membered ring.

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(valence double ζ) with SBKJC eﬀective core potentials was used for

all Pd atoms.³⁴Bond lengths and angles and all energy values were

extracted from the geometry optimization output using GaussView 5.0.

General Procedure for the Syntheses of 2-Bromobenzyl-

phosphinite-boranes 9. A freshly titrated toluene solution of dry

HCl (12 or 30 mmol in the case of R¹= Fc) was added to the

corresponding aminophosphine boranes¹⁸(2 mmol), and the reaction

was stirred at room temperature for 2 h (or 48 h in the case of R¹=

Fc). The ephedrine hydrochloride was ﬁltered oﬀ using a Millipore 4

μm ﬁlter. The resulting solution of chlorophosphine boranes 7a−e was

collected and cooled to −78 °C. Alcoholate (4 mmol), previously

prepared by reaction between 2-bromobenzyl alcohol (4 mmol) and

NaH (4.4 mmol) in THF (3 mL) at 0 °C for 1 h, was added, and the

resulting mixture was stirred at room temperature overnight. After

hydrolysis with water (10 mL), the mixture was extracted with

methylene chloride (3 × 10 mL) and the combined organic phases

were dried over MgSO₄. The solvent was removed under vacuum, and

the resulting crude product was puriﬁed by chromatography on silica

gel or by recrystallization in methyl alcohol.

(R)-2-Bromobenzyl(2-methoxylphenyl)phenylphosphinite-bor-

ane, 9a. The puriﬁcation was achieved by recrystallization in methyl

alcohol. White solid; yield 71% (0.59 g); mp 90−92 °C; R_f0.31

(petroleum ether/ethyl acetate, 5:1); 99% ee determined by HPLC

analysis on Lux 5 μm cellulose-2 chiral column, 0.5 mL·min⁻¹, hexane/

2-propanol, 98:2; t_R(S) = 20.7 min, t_R(R) = 22.1 min; [α]_D= −1.4 (c

0.4, CHCl₃); ¹H NMR (300 MHz, CDCl₃) δ 3.63 (s, 3H), 5.08−5.16

(m, 2H), 6.87 (dd, J = 4.2, 8.5 Hz, 1H), 7.08 (tdd, J = 0.9, 2.0, 7.5 Hz,

1H), 7.17 (td, J = 1.7, 7.5 Hz, 1H), 7.30 (td, J = 1.2, 7.5 Hz, 1H),

7.43−7.56 (m, 6H), 7.78−7.88 (m, 3H); ¹³C NMR (125.8 MHz,

CDCl₃) δ 55.4, 68.0, 111.5 (d, J = 6.3 Hz), 119.4 (d, J = 61.0 Hz),

120.8 (d, J = 10.5 Hz), 122.6, 127.4, 128.1 (d, J = 10.8 Hz), 129.4 (d, J

= 3.6 Hz), 131.2, 131.3, 131.4 (d, J = 2.0 Hz), 132.0 (d, J = 66.5 Hz),

132.5, 134.1 (d, J = 11.6 Hz), 134.2, 136.7 (d, J = 7.8 Hz), 161.0 (d, J

= 3.0 Hz); ³¹P NMR (121.5 MHz, CDCl₃) δ + 106.2 (brs); HRMS

calcd for C₂₀H₂₁PO₂BBrNa [M + Na]⁺, 437.0447; found, 437.0451.

(R)-2-Bromobenzyl(2-methylphenyl)phenylphosphinite-borane,

9b. The puriﬁcation was accomplished by chromatography on silica

gel using a mixture of petroleum ether/ethyl acetate (5:1) as eluent.

Colorless oil; yield 74% (0.59 g); R_f0.41 (petroleum ether/ethyl

acetate, 5:1); 99% ee determined by HPLC analysis on Lux 5 μm

cellulose-2, 0.5 mL·min⁻¹, hexane/2-propanol, 98:2, t_R(S) = 11.5 min,

t_R(R) = 12.3 min; [α]_D= +11.7 (c 0.3, CHCl₃); ¹H NMR (500 MHz,

CDCl₃) δ 2.27 (s, 3H), 5.11 (ABX syst, J = 6.5, 12.3 Hz, 1H), 5.17

(ABX syst, J = 7.2, 12.3 Hz, 1H), 7.18−7.23 (m, 2H), 7.30−7.37 (m,

2H), 7.44−7.58 (m, 6H), 7.69−7.73 (m, 2H), 7.98 (ddd, J = 1.0, 7.7,

12.9 Hz, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ 21.4 (d, J = 4.2 Hz),

68.2, 123.1, 125.7 (d, J = 10.0 Hz), 127.5, 128.6 (d, J = 10.0 Hz), 129.3

(d, J = 56.7 Hz), 129.7, 129.9, 131.2 (d, J = 10.0 Hz), 131.6, 131.7 (d, J

= 3.3 Hz), 131.8, 132.4, 132.8, 133.8 (d, J = 15.3 Hz), 136.2 (d, J =

10.0 Hz), 142.1 (d, J = 6.7 Hz); ³¹P NMR (202.5 MHz, CDCl₃) δ +

109.8 (brs); HRMS calcd for C₂₀H₂₁POBBrNa [M + Na]⁺, 421.0502;

found, 421.0486.

EXPERIMENTAL SECTION

■

General Considerations. All reactions were carried out using

standard Schlenk techniques under an inert atmosphere. Solvents were

dried and puriﬁed by conventional methods prior to use.

Tetrahydrofuran (THF) and toluene were distilled from sodium/

benzophenone and stored under argon. Methylene chloride (CH₂Cl₂)

was distilled from CaH₂under argon prior to use. Hexane and 2-

propanol for HPLC were of chromatographic grade and used without

puriﬁcation. n-Butyllithium, tert-butyllithium, 2-bromobenzyl alcohol,

methanesulfonyl chloride, triethylamine, carbon tetrabromide, triphe-

nylphosphine, 1,4-diazabicyclo[2.2.2]octane (DABCO), dichlorobis-

(acetonitrile)palladium, dimethylmalonate, benzylamine, benzyl alco-

hol, tetrabutylammonium ﬂuoride (1 M in THF; TBAF), and N,O-

bis(trimethylsilyl)acetamide (BSA) were purchased from commercial

sources. Thiophenol, ethanethiol, 2-methyl-2-propanethiol, o-toluene-

thiol, 2-methoxythiophenol, 4-methoxythiophenol, 2,6-dimethyl-

thiophenol, 3,5-dimethylthiophenol, and triisopropyl silanethiol are

commercially available. Chlorophosphine boranes 7 were prepared

from the corresponding aminophosphine boranes according to the

ephedrine methodology.¹⁸2-Bromophenethyl alcohol was prepared

using a literature procedure,²⁶o-anisylphenyl-phenylphosphinite

borane 15 was synthesized as previously described by our

group.^15b,18,212-Bromophenyl(phenyl)sulﬁde (16a) and 2-

bromophenyl(tert-butyl)sulﬁde (16b) were prepared according to a

literature procedure.²⁷(E)-1,3-Diphenylprop-2-en-1-yl acetate (17),

(E)-1-propylhex-2-en-1-yl acetate (18), and cyclohexenyl acetate (19)

were synthesized according to a procedure described.²⁸Reactions were

monitored by thin-layer chromatography (TLC) using 0.25 mm

precoated silica gel plates. Flash chromatography was performed with

1

the indicated solvents using silica gel 60 (35−70 μm mesh). H (and

¹H decoupled), ¹³C, and ³¹P NMR spectra were recorded at 600, 500,

or 300 MHz, 151, 125.8, or 75.5 MHz, and 243, 202.5, or 121.5 MHz,

respectively, using TMS as an internal reference for ¹H and ¹³C NMR

and 85% phosphoric acid as external reference for ³¹P NMR. Data are

reported as s = singlet, d = doublet, t = triplet, q = quartet, m =

multiplet, brs = broad singlet; coupling constant(s) in hertz; and

integration. HPLC analyses were performed on a chromatograph

equipped with a UV detector at λ = 210 and 254 nm. Melting points

were measured on a Koﬂer melting point apparatus and are

uncorrected. Optical rotation values were measured at 20 °C on a

polarimeter at 589 nm (sodium lamp). High-resolution mass spectra

(HRMS) were recorded on a mass spectrometer under electron spray

ionization (ESI) conditions, with a micro-Q-TOF or orbitrap detector.

Crystal Structure Determination. Diﬀraction data were collected

on a Nonius Kappa APEX II diﬀractometer equipped with a nitrogen

jet stream low-temperature system (Oxford Cryosystems). The X-ray

source was graphite-monochromated Mo Kα1 radiation (λ = 0.710 73

Å) from a sealed tube. The lattice parameters were obtained by least-

squares ﬁtting to the optimized setting angles of the entire set of

collected reﬂections. No signiﬁcant temperature drift was observed

during the data collections. Data were reduced by using SAINT²⁹

software with applying multiscan absorption corrections. The structure

was solved by the charge-ﬂipping method using the SUPERFLIP³⁰

program. Reﬁnements were carried out by full-matrix least-squares on

F², using the SHELX³¹program on the complete set of reﬂections.

Anisotropic thermal parameters were used for non-hydrogen atoms.

All H atoms, on carbon or oxygen atoms, were placed at calculated

positions using a riding model with C−H = 0.95 (aromatic), 0.99

(methylene), or 0.98 (methyle) with U_iso(H) = 1.2U_eq(CH), U_iso(H) =

1.2U_eq(CH₂), or U_iso(H) = 1.2U_eq(CH₃). Absolute conﬁgurations of

all compounds were determined reliably from anomalous scattering,

using the Flack¹⁹method. Crystallographic data are available in the

Supporting Information.

(R)-2-Bromobenzyl-(o-biphenyl)phenylphosphinite-borane, 9c.

The puriﬁcation was achieved by chromatography on silica gel using

a mixture of petroleum ether/ethyl acetate (5:1) as eluent. White

solid; yield 63% (0.58 g); R_f0.59 (petroleum ether/ethyl acetate, 5:1);

1

[α]_D= +23.3 (c 0.3, CHCl₃); H NMR (500 MHz, CDCl₃) δ 4.92−

5.05 (m, 2H), 6.88−6.93 (m, 2H), 7.01−7.06 (m, 2H), 7.14−7.26 (m,

5H), 7.30−7.39 (m, 5H), 7.49−7.62 (m, 3H), 8.13−8.20 (m, 1H); ¹³C

NMR (125.8 MHz, CDCl₃) δ 68.2, 122.7, 127.1 (d, J = 11.4 Hz),

127.2, 127.4, 128.1 (d, J = 10.7 Hz), 129.5, 129.6, 130.0, 130.5, 130.9,

131.0, 131.1 (d, J = 2.4 Hz), 131.6−131.7 (m), 131.8, 132.1, 132.6,

133.7 (d, J = 15.5 Hz), 136.2 (d, J = 8.4 Hz), 140.2 (d, J = 3.4 Hz),

146.8 (d, J = 8.4 Hz); ³¹P NMR (202.5 MHz, CDCl₃) δ + 108.7 (brs);

HRMS calcd for C₂₅H₂₀POBBrNa [M + Na]⁺, 483.0660; found,

483.0646.

Computational Details. All density functional theory (DFT)

calculations were performed with Gaussian 09³²at the Universite

́

de

Sherbrooke with the Mammouth supercomputer supported by Le

(R)-2-Bromobenzylferrocenylphenylphosphinite-borane, 9d. The

puriﬁcation was achieved by chromatography on silica gel using a

mixture of petroleum ether/ethyl acetate (4:1) as eluent. Orange oil;

yield 51% (0.50 g); R_f0.43 (petroleum ether/ethyl acetate, 4:1); [α]_D

́ ́ ́

Reseau Quebecois De Calculs Hautes Performances. The DFT

geometry optimizations³³were carried out using the B3LYP method.

A 6-31G* basis set was used for C, H, S, P, and Cl atoms.³⁴VDZ

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= +10.3 (c 0.3, CHCl₃); ¹H NMR (300 MHz, CDCl₃) δ 4.17 (s, 5H),

4.36−4.37 (m, 1H), 4.46−4.48 (m, 1H), 4.51−4.53 (m, 1H), 4.71−

4.72 (m, 1H), 4.96 (ABX syst, J = 6.4, 12.8 Hz, 1H), 5.10 (ABX syst, J

= 6.9, 12.8 Hz, 1H), 7.17 (td, J = 1.7, 7.9 Hz, 1H), 7.31 (td, J = 1.3, 7.6

Hz, 1H), 7.47−7.57 (m, 5H), 7.91−7.98 (m, 2H); ¹³C NMR (75.5

MHz, CDCl₃) δ 67.8 (d, J = 1.5 Hz), 70.0, 71.3 (d, J = 79.4 Hz), 71.7

(d, J = 8.2 Hz), 71.9 (d, J = 7.3 Hz), 72.1 (d, J = 8.5 Hz), 122.6, 127.5,

128.5 (d, J = 9.1 Hz), 129.4 (d, J = 3.8 Hz), 131.1, 131.2, 131.8, 131.9

(d, J = 2.5 Hz), 132.6, 136.5 (d, J = 8.2 Hz); ³¹P NMR (121.5 MHz,

CDCl₃) δ + 107.8 (brs); HRMS calcd for C₂₃H₂₃POBBrFeNa [M +

Na]⁺, 515.0011; found, 515.0022.

analysis on Lux 5 μm cellulose-1, 1.0 mL·min⁻¹, hexane/2-propanol,

98:2, t_R(R) = 50.0 min, t_R(S) = 53.9 min; [α]_D= +3.4 (c 0.3, CHCl₃);

¹H NMR (300 MHz, CDCl₃) δ 2.55 (brs, 1H), 3.56 (s, 3H), 4.60 (brs,

2H), 6.97 (dd, J = 3.6, 8.2 Hz, 1H), 7.04−7.14 (m, 2H), 7.25 (tt, J =

1.4, 7.3 Hz, 1H), 7.42−7.68 (m, 9H); ¹³C NMR (75.5 MHz, CDCl₃) δ

55.4, 63.2 (d, J = 5.8 Hz), 111.9 (d, J = 4.4 Hz), 117.0 (d, J = 57.3 Hz),

121.4 (d, J = 11.0 Hz), 127.4 (d, J = 9.1 Hz), 127.5 (d, J = 56.6 Hz),

128.5 (d, J = 10.6 Hz), 129.3 (d, J = 59.7 Hz), 130.9 (d, J = 9.1 Hz),

131.1 (d, J = 1.5 Hz), 131.3 (d, J = 3.0 Hz), 133.3−133.4 (m), 134.0

(d, J = 1.8 Hz), 135.4 (d, J = 10.9 Hz), 144.7 (d, J = 12.2 Hz), 161.5;

³¹P NMR (121.5 MHz, CDCl₃) δ + 16.4 (brs); HRMS calcd for

C₂₀H₂₂PO₂BNa [M + Na]⁺, 359.1346; found, 359.1346.

(R)-2-Bromobenzyl(3,5-dimethylphenyl)phenylphosphinite-bor-

ane, 9e. The puriﬁcation was achieved by chromatography on silica

gel using a mixture of petroleum ether/ethyl acetate (5:1) as eluent.

White solid; yield 74% (0.61 g); mp 56−58 °C; R_f0.41 (petroleum

ether/ethyl acetate, 5:1); [α]_D= +14.5 (c 0.4, CHCl₃); ¹H NMR (500

MHz, CDCl₃) δ 2.36 (s, 6H), 5.12 (2ABX syst, J = 6.9, 12.4 Hz), 7.17

(brs, 1H), 7.20 (td, J = 1.9, 7.8 Hz, 1H), 7.32 (td, J = 0.9, 7.4 Hz, 1H),

7.40 (brs, 1H), 7.42 (brs, 1H), 7.46−7.58 (m, 5H), 7.78−7.82 (m,

2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 21.3, 68.2, 123.0, 127.5, 128.6

(d, J = 8.0 Hz), 129.0 (d, J = 10.6 Hz), 129.6, 129.8, 131.2 (d, J = 63.8

Hz), 131.3 (d, J = 10.6 Hz), 131.8, 132.1 (d, J = 63.8 Hz), 132.7, 133.8

(d, J = 1.7 Hz), 136.2 (d, J = 8.0 Hz), 138.4 (d, J = 10.6 Hz); ³¹P NMR

(202.5 MHz, CDCl₃) δ + 107.3 (brs); HRMS calcd for

C₂₁H₂₀POBrNa [M − BH₃+ Na]⁺, 421.0327; found, 421.0320.

(R)-(2-Methoxyphenyl)-(2-bromophenethyl)phenylphosphinite-

borane, 9f. A freshly titrated toluene solution of dry HCl (12 mmol)

was added to aminophosphine-borane (0.79 g, 2 mmol), and the

reaction was stirred at room temperature for 2 h. The ephedrine

hydrochloride was ﬁltered oﬀ using a Millipore 4 μm ﬁlter. The

resulting solution of chlorophosphine-borane 7a was collected and

cooled to −78 °C. Alcoholate (4 mmol), previously prepared by

reaction between 2-bromophenethyl alcohol (0.80 g, 4 mmol) and

NaH (0.11 g, 4.4 mmol) in THF (3 mL) at 0 °C for 1 h, was added,

and the resulting mixture was stirred at room temperature overnight.

After hydrolysis with water (10 mL), the mixture was extracted with

methylene chloride (3 × 10 mL), and the combined organic phases

were dried over MgSO₄. The solvent was removed under vacuum, and

the resulting crude product was puriﬁed by chromatography on silica

gel using a mixture of petroleum ether/ethyl acetate (5:1) as eluent.

Colorless oil; yield 73% (0.63 g); R_f0.40 (petroleum ether/ethyl

acetate, 5:1); 99% ee determined by HPLC analysis on Lux 5 μm

cellulose-2, 0.5 mL·min⁻¹, hexane/2-propanol, 98:2, t_R(S) = 18.3 min,

t_R(R) = 19.3 min; [α]_D= −13.1 (c 0.4, CHCl₃); ¹H NMR (600 MHz,

CDCl₃) δ 3.19 (t, J = 7.0 Hz, 2H), 3.61 (s, 3H), 4.20−4.29 (m, 2H),

6.87 (dd, J = 4.4, 8.3 Hz, 1H), 7.07 (tdd, J = 0.8, 1.9, 7.5 Hz, 1H), 7.12

(td, J = 1.7, 7.8 Hz, 1H), 7.24 (td, J = 1.2, 7.5 Hz, 1H), 7.30 (dd, J =

1.7, 7.6 Hz, 1H), 7.40−7.43 (m, 2H), 7.47−7.52 (m, 2H), 7.55 (dd, J

= 1.1, 7.9 Hz, 1H), 7.69−7.72 (m, 2H), 7.77 (ddd, J = 1.7, 7.5, 12.2

Hz, 1H); ¹³C NMR (151 MHz, CDCl₃) δ 37.4 (d, J = 6.8 Hz), 55.4,

65.8 (d, J = 2.5 Hz), 111.6 (d, J = 5.7 Hz), 119.8 (d, J = 65.2 Hz),

120.8 (d, J = 11.3 Hz), 124.7, 127.4, 128.0 (d, J = 11.3 Hz), 128.3,

131.1, 131.2, 131.5, 132.4 (d, J = 66.0 Hz), 132.8, 133.8 (d, J = 10.7

Hz), 134.0, 137.1, 161.0 (d, J = 3.4 Hz); ³¹P NMR (243 MHz, CDCl₃)

δ + 104.0 (brs); HRMS calcd for C₂₁H₂₃PBBrO₂Na [M + Na]⁺,

451.0608; found, 451.0607.

( R ) - ( 2 - H y d r o x y m e t h y l p h e n y l ) - ( 2 - m e t h y l p h e n y l ) -

phenylphosphine-borane, 10b. The puriﬁcation was achieved by

chromatography on silica gel using a mixture of petroleum ether/ethyl

acetate (2:1) as eluent. White sticky solid; yield 80% (0.10 g); R_f0.37

(petroleum ether/ethyl acetate, 2:1); 99% ee determined by HPLC

analysis on Lux 5 μm cellulose-1, 1.0 mL·min⁻¹, hexane/2-propanol,

98:2, t_R(R) = 29.1 min, t_R(S) = 31.9 min; [α]_D= +3.7 (c 0.3, CHCl₃);

¹H NMR (500 MHz, CDCl₃) δ 2.38 (s, 3H), 4.65 (AB syst, J = 13.4

Hz, 1H), 4.69 (AB syst, J = 13.4 Hz, 1H), 6.99−7.04 (m, 2H), 7.19 (t,

J = 7.7 Hz, 1H), 7.24−7.34 (m, 2H), 7.43−7.51 (m, 3H), 7.56−7.59

(m, 4H); ¹³C NMR (125.8 MHz, CDCl₃) δ 22.7 (d, J = 4.8 Hz), 63.4

(d, J = 6.2 Hz), 126.1 (d, J = 9.5 Hz), 127.4, 127.5 (d, J = 53.6 Hz),

127.9 (d, J = 8.3 Hz), 128.4, 129.0 (d, J = 10.1 Hz), 131.4 (d, J = 9.0

Hz), 131.5 (d, J = 2.1 Hz), 131.6 (d, J = 2.1 Hz), 131.9 (d, J = 1.4 Hz),

132.1 (d, J = 9.0 Hz), 133.4 (d, J = 6.2 Hz), 133.6 (d, J = 9.7 Hz),

133.7, 143.2 (d, J = 10.7 Hz), 145.4 (d, J = 10.7 Hz); ³¹P NMR (202.5

MHz, CDCl₃) δ + 18.7 (brs); HRMS calcd for C₂₀H₂₂POBNa [M +

Na]⁺, 343.1397; found, 343.1383.

(S)-Ferrocenyl-(2-hydroxymethylphenyl)phenylphosphine-bor-

ane, 10d.^17a,bThe puriﬁcation was achieved by chromatography on

silica gel using a mixture of petroleum ether/ethyl acetate (1:1) as

eluent and recrystallization in dichloromethane/hexane. Orange solid;

yield 58% (0.10 g); mp 158−160 °C; R_f0.44 (petroleum ether/ethyl

acetate, 1:1); 99% ee determined by HPLC analysis on a Chiralcel

OD-H, 0.7 mL·min⁻¹, hexane/2-propanol, 95:5, t_R(R) = 21.3 min,

t_R(S) = 25.1 min; [α]_D= +194.3 (c 0.2, CHCl₃); ¹H NMR (300 MHz,

CDCl₃) δ 2.01 (dd, J = 5.7, 8.2 Hz, 1H), 4.08−4.09 (m, 1H), 4.10 (s,

5H), 4.23 (dd, J = 9.0, 13.6 Hz, 1H), 4.54 (brs, 1H), 4.63−4.64 (m,

1H), 4.66 (dd, J = 5.7, 13.6 Hz, 1H), 4.75 (brs, 1H), 7.08 (dd, J = 8.4,

12.2 Hz, 1H), 7.24 (t, J = 7.5 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.52−

7.61 (m, 4H), 7.77−7.80 (m, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ

62.9 (d, J = 5.8 Hz), 69.5 (d, J = 71.7 Hz), 69.9, 71.7 (d, J = 3.8 Hz),

72.1 (d, J = 6.7 Hz), 72.2 (d, J = 4.8 Hz), 74.5 (d, J = 16.3 Hz), 127.3

(d, J = 9.2 Hz), 128.8 (d, J = 11.2 Hz), 130.0 (d, J = 54.9 Hz), 130.3

(d, J = 9.2 Hz), 130.7 (d, J = 59.0 Hz), 131.4 (d, J = 2.0 Hz), 131.5 (d,

J = 2.0 Hz), 132.6 (d, J = 9.2 Hz), 133.0 (d, J = 7.1 Hz), 144.0 (d, J =

10.5 Hz); ³¹P NMR (121.5 MHz, CDCl₃) δ + 15.0 (brs); HRMS calcd

for C₂₃H₂₁POFeNa [M − BH₃+ Na]⁺, 423.0572; found 423.0562.

(R)-(2-Hydroxymethylphenyl)-(3,5-dimethylphenyl)-

phenylphosphine-borane, 10e. Puriﬁcation was achieved by

chromatography on silica gel using petroleum ether/ethyl acetate

(2:1) as eluent. White sticky solid; yield 80% (0.11 g); R_f0.44

(petroleum ether/ethyl acetate, 2:1); 99% ee determined by HPLC

analysis on Lux 5 μm cellulose-2, 0.7 mL·min⁻¹, hexane/2-propanol,

90:10, t_R(S) = 16.3 min, t_R(R) = 18.4 min; [α]_D= −5.1 (c 0.3,

CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 2.33 (s, 6H), 2.51 (brs, 1H),

4.59−4.64 (m, 2H), 6.97 (dd, J = 7.3, 11.5 Hz, 1H), 7.17−7.19 (m,

3H), 7.26−7.29 (m, 1H), 7.47−7.50 (m, 2H), 7.54−7.61 (m, 4H),

7.66 (ddd, J = 0.7, 4.2, 7.6 Hz, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ

21.3, 63.2 (d, J = 5.7 Hz), 127.6 (d, J = 53.4 Hz), 127.7 (d, J = 8.4 Hz),

128.5 (d, J = 57.7 Hz), 128.9 (d, J = 11.3 Hz), 129.3 (d, J = 57.7 Hz),

130.7 (d, J = 9.8 Hz), 131.0 (d, J = 8.4 Hz), 131.4 (d, J = 1.4 Hz),

131.8 (d, J = 2.8 Hz), 133.2 (d, J = 9.8 Hz), 133.4 (d, J = 2.8 Hz),

134.1 (d, J = 7.0 Hz), 138.7 (d, J = 10.1 Hz), 145.2 (d, J = 10.1 Hz);

³¹P NMR (202.5 MHz, CDCl₃) δ + 17.8 (brs); HRMS calcd for

Synthesis of (2-Hydroxymethylphenyl)phosphine-boranes

10. General Procedure. To a solution of 2-bromobenzylphosphin-

ite-borane 9 (0.40 mmol) in dry THF (4 mL) was added dropwise at

−78 °C 1.7 mL of t-BuLi (1.08 mmol, 1.6 M in pentane). The reaction

mixture was stirred for 1 h 30 and warmed to 0 °C, quenched with

saturated ammonium chloride solution (5 mL), and extracted with

dichloromethane (3 × 10 mL). The combined organic phases were

dried over MgSO₄, and the solvent was removed under vacuum to give

a residue, which was puriﬁed by chromatography on silica gel.

(S)-(2-Hydroxymethylphenyl)-(2-methoxyphenyl)-

phenylphosphine-borane, 10a. The puriﬁcation was achieved by

chromatography on silica gel using a mixture of petroleum ether/ethyl

acetate (1:1). White sticky solid; yield 62% (0.08 g); R_f0.47

(petroleum ether/ethyl acetate, 1:1); 99% ee determined by HPLC

C₂₁H₂₁PONa [M − BH₃+ Na]⁺, 343.1222; found, 343.1217.

(S)-[2-(Hydroxyethyl)phenyl]-(2-methoxylphenyl)-

phenylphosphine-borane, 10f. To a solution of phosphinite-borane

I

DOI: 10.1021/acs.organomet.5b00585

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9f (0.17 g, 0.40 mmol) in dry THF (4 mL) was added dropwise at

−78 °C 1.7 mL of t-BuLi (1.08 mmol, 1.6 M in pentane). The reaction

mixture was stirred for 1 h 30 and warmed to 0 °C, then quenched

with saturated ammonium chloride solution (5 mL) and extracted with

dichloromethane (3 × 10 mL). The combined organic phases were

dried over MgSO₄, and the solvent was removed under vacuum to give

a residue, which was puriﬁed by chromatography on silica gel using a

mixture of petroleum ether/ethyl acetate (2:1) as eluent. White sticky

solid; yield 70% (0.10 g); R_f0.18 (petroleum ether/ethyl acetate, 2:1);

99% ee determined by HPLC analysis on Lux 5 μm cellulose-1, 1.0

mL·min⁻¹, hexane/2-propanol, 90:10, t_R(S) = 11.7 min, t_R(R) = 12.6

Hz, 1H), 7.30 (tt, J = 1.5, 7.7 Hz, 1H), 7.47−7.61 (m, 5H), 7.78−7.84

(m, 2H); ¹³C NMR (75.5 MHz, CDCl₃) δ 37.1, 68.9 (d, J = 5.6 Hz),

69.0 (d, J = 73.6 Hz), 69.9, 71.5 (d, J = 4.3 Hz), 72.2 (d, J = 9.9 Hz),

72.4 (d, J = 6.2 Hz), 74.6 (d, J = 17.4 Hz), 128.5 (d, J = 7.3 Hz), 128.9

(d, J = 9.1 Hz), 129.8 (d, J = 60.0 Hz), 130.3 (d, J = 9.1 Hz), 130.9,

131.3 (d, J = 2.3 Hz), 131.8 (d, J = 2.8 Hz), 132.9 (d, J = 9.6 Hz),

133.2 (d, J = 7.3 Hz), 136.5 (d, J = 8.6 Hz); ³¹P NMR (121.5 MHz,

CDCl₃) δ + 16.4 (brs); HRMS calcd for C₂₄H₂₆PO₃BSFeNa [M +

Na]⁺, 515.0680; found, 515.0690.

(R)-[2-(Methanesulfonatomethyl)phenyl]-(3,5-dimethylphenyl)-

phenylphosphine-borane, 11e. The puriﬁcation was achieved by

chromatography on silica gel using dichloromethane as eluent. White

1

min; [α]_D= −13.8 (c 0.3, CHCl₃); H NMR (500 MHz, CDCl₃) δ

sticky solid; yield 83% (0.27 g); R_f0.46 (dichloromethane); [α]_D

=

2.93−3.01 (m, 2H), 3.56 (s, 3H), 3.73 (td, J = 1.2, 6.9 Hz, 2H), 6.95

(dd, J = 3.9, 8.3 Hz, 1H), 7.07 (tdd, J = 0.8, 1.8, 7.7 Hz, 1H), 7.14−

7.21 (m, 2H), 7.37−7.61 (m, 7H), 7.65−7.69 (m, 2H); ¹³C NMR

(125.8 MHz, CDCl₃) δ 37.7 (d, J = 6.9 Hz), 55.4, 63.4, 111.9 (d, J =

3.5 Hz), 117.4 (d, J = 58.2 Hz), 121.3 (d, J = 10.6 Hz), 126.1 (d, J =

8.7 Hz), 127.9, 128.4 (d, J = 10.4 Hz), 129.4 (d, J = 8.9 Hz), 130.7 (d,

J = 9.1 Hz), 130.8 (d, J = 1.9 Hz), 130.9 (d, J = 2.2 Hz), 133.4 (d, J =

10.4 Hz), 133.8−133.9 (m), 135.4 (d, J = 10.4 Hz), 142.8 (d, J = 12.0

Hz), 161.5; ³¹P NMR (202.5 MHz, CDCl₃) δ + 17.9 (brs); HRMS

calcd for C₂₁H₂₄PBO₂Na [M + Na]⁺, 373.1503; found, 373.1495.

Syntheses of Mesylate Derivatives 11a−f. General Proce-

dure. To a solution of (2-hydroxyphenyl)phosphine-borane 10 (0.80

mmol) in dry CH₂Cl₂(6 mL) were added successively at 0 °C

triethylamine (1.60 mmol) and methanesulfonyl chloride (1.3 mmol).

The reaction mixture was stirred at room temperature for 2 h, then

quenched with water (10 mL), and extracted with dichloromethane (3

× 10 mL). The combined organic phases were dried over MgSO₄, and

the solvent was removed under vacuum to give a residue, which was

puriﬁed by chromatography on silica gel.

1

+22.2 (c 0.2, CHCl₃); H NMR (600 MHz, CDCl₃) δ 2.35 (s, 6H),

2.72 (s, 3H), 5.36 (2AB syst, J = 12.1 Hz, 2H), 7.03 (ddd, J = 1.1, 7.8,

11.6 Hz, 1H), 7.20 (brs, 2H), 7.23 (brs, 1H), 7.36 (tt, J = 1.3, 7.6 Hz,

1H), 7.50−7.53 (m, 2H), 7.57−7.65 (m, 4H), 7.71 (ddd, J = 0.7, 4.2,

7.7 Hz, 1H); ¹³C NMR (151 MHz, CDCl₃) δ 21.3, 37.0, 69.3 (d, J =

5.4 Hz), 127.8 (d, J = 60.4 Hz), 128.5 (d, J = 3.9 Hz), 128.9, 129.0 (d,

J = 8.4 Hz), 129.1 (d, J = 10.2 Hz), 130.8 (d, J = 9.7 Hz), 131.0 (d, J =

7.9 Hz), 131.7 (d, J = 1.8 Hz), 131.8, 133.4 (d, J = 9.9 Hz), 133.6 (d, J

= 2.1 Hz), 134.2 (d, J = 6.4 Hz), 137.8 (d, J = 10.0 Hz), 139.0 (d, J =

10.7 Hz); ³¹P NMR (243 MHz, CDCl₃) δ + 19.3 (brs); HRMS calcd

for C₂₂H₂₆PO₃BSNa [M + Na]⁺, 435.1330; found, 435.1323.

(R)-[2-(Methanesulfonatomethyl)phenyl]-(o-biphenyl)-

phenylphosphine-borane, 11c. To a solution of phosphinite-borane

9c (0.46 g, 1.00 mmol) in dry THF (10 mL) was added dropwise 1.7

mL of t-BuLi (2.7 mmol, 1.6 M in pentane) at −78 °C. The reaction

mixture was stirred for 1 h 30 and warmed to 0 °C, then quenched

with a saturated ammonium chloride solution (10 mL), and extracted

with dichloromethane (3 × 10 mL). The combined organic phases

were dried over MgSO₄, and the solvent was removed under vacuum

to give a residue, which was ﬁltered on a plug of silica (elution with

petroleum ether/ethyl acetate, 2:1), then dissolved in dichloromethane

(4 mL). To this solution were successively added triethylamine (0.28

mL, 2.00 mmol) and methanesulfonyl chloride (0.12 mL, 1.6 mmol) at

0 °C, and the reaction mixture was stirred to room temperature for 2

h. Water (2 mL) was added, and the solution was extracted with

dichloromethane (3 × 5 mL). The combined organic phases were

dried over MgSO₄, and the solvent was removed under vacuum to give

a residue, which was puriﬁed by chromatography using dichloro-

methane as eluent. The corresponding mesylate 11c, which was

obtained as a white unstable solid, was used immediately for the next

step: white solid; overall yield (two steps) 34% (0.16 g); R_f0.42

(dichloromethane); ¹H NMR (500 MHz, CDCl₃) δ 2.76 (s, 3H), 5.30

(AB syst, J = 11.9 Hz, 1H), 5.37 (AB syst, J = 11.9 Hz, 1H), 6.85−6.86

(m, 2H), 7.00 (ddd, J = 1.0, 7.6, 11.2 Hz, 1H), 7.06 (t, J = 8.0 Hz, 2H),

7.20 (tt, J = 1.1, 7.4 Hz, 1H), 7.26 (t, J = 7.4 Hz, 1H), 7.36 (ddd, J =

1.1, 4.0, 7.6 Hz, 1H), 7.43−7.65 (m, 10H); ¹³C NMR (125.8 MHz,

CDCl₃) δ 37.1, 69.6 (d, J = 4.8 Hz), 126.8 (d, J = 52.9 Hz), 127.5 (d, J

= 9.2 Hz), 127.5, 127.6, 128.8 (d, J = 8.4 Hz), 128.9 (d, J = 10.4 Hz),

129.3 (d, J = 26.9 Hz), 129.6, 129.7 (d, J = 21.0 Hz), 130.9 (d, J = 8.1

Hz), 131.3 (d, J = 1.9 Hz), 131.4 (d, J = 1.9 Hz), 131.5 (d, J = 2.3 Hz),

132.6 (d, J = 8.0 Hz), 133.6 (d, J = 9.6 Hz), 134.0 (d, J = 6.4 Hz),

134.8 (d, J = 8.0 Hz), 137.4 (d, J = 11.0 Hz), 140.2 (d, J = 3.4 Hz),

148.2 (d, J = 11.0 Hz); ³¹P NMR (202.5 MHz, CDCl₃) δ + 21.4 (brs);

HRMS calcd for C₂₆H₂₆PO₃BSNa [M + Na]⁺, 483.1330; found,

483.1309.

(S)-[2-(Methanesulfonatomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane, 11a. The puriﬁcation was achieved by

chromatography on silica gel using a mixture of petroleum ether/ethyl

acetate (3:1) as eluent. Colorless oil; yield 77% (0.26 g); R_f0.23

(petroleum ether/ethyl acetate, 3:1); [α]_D= −40.0 (c 0.3, CHCl₃); ¹H

NMR (500 MHz, CDCl₃) δ 2.69 (s, 3H), 3.55 (s, 3H), 5.33 (brs, 2H),

6.98 (ddd, J = 0.5, 3.7, 8.2 Hz, 1H), 7.11 (tdd, J = 1.0, 2.2, 7.7 Hz, 1H),

7.17 (ddd, J = 1.2, 7.8, 12.1 Hz, 1H), 7.33 (tt, J = 1.4, 7.8 Hz, 1H),

7.46−7.50 (m, 2H), 7.53−7.60 (m, 3H), 7.66 (ddd, J = 0.9, 4.2, 7.7

Hz, 1H), 7.73−7.77 (m, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 36.9,

55.4, 69.5 (d, J = 5.5 Hz), 112.0 (d, J = 4.4 Hz), 116.4 (d, J = 57.0 Hz),

121.5 (d, J = 12.1 Hz), 128.2, 128.6, 128.7, 129.3 (d, J = 54.6 Hz),

130.8 (d, J = 8.3 Hz), 131.1 (d, J = 1.7 Hz), 131.4 (d, J = 2.2 Hz),

133.1 (d, J = 6.9 Hz), 133.7 (d, J = 10.2 Hz), 134.3 (d, J = 1.9 Hz),

135.5 (d, J = 11.9 Hz), 136.8 (d, J = 10.2 Hz), 161.5; ³¹P NMR (202.5

MHz, CDCl₃) δ + 17.2 (brs); HRMS calcd for C₂₁H₂₄PO₄BSNa [M −

BH₃+ Na]⁺, 437.1239; found, 437.1246.

(R)-[2-(Methanesulfonatomethyl)phenyl]-(2-methylphenyl)-

phenylphosphine-borane, 11b. The puriﬁcation was achieved by

chromatography on silica gel using dichloromethane as eluent. White

sticky solid; yield 68% (0.22 g); R_f0.43 (dichloromethane); [α]_D

=

+9.9 (c 0.4, CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 2.36 (s, 3H), 2.74

(s, 3H), 5.44 (AB syst, J = 11.9 Hz, 1H), 5.48 (AB syst, J = 11.9 Hz,

1H), 7.05−7.12 (m, 2H), 7.22 (t, J = 7.8 Hz, 1H), 7.33−7.38 (m, 2H),

7.45−7.53 (m, 3H), 7.56−7.63 (m, 4H), 7.73−7.76 (m, 2H); ¹³C

NMR (125.8 MHz, CDCl₃) δ 22.7, 37.1, 69.6 (d, J = 4.9 Hz), 126.2 (d,

J = 10.5 Hz), 127.1 (d, J = 55.5 Hz), 128.1 (d, J = 58.5 Hz), 128.7,

129.0, 129.1, 131.2 (d, J = 7.4 Hz), 131.7, 131.9, 132.9 (d, J = 7.4 Hz),

133.6 (d, J = 5.6 Hz), 133.8, 133.9, 138.1 (d, J = 11.4 Hz), 143.3 (d, J

= 11.4 Hz); ³¹P NMR (202.5 MHz, CDCl₃) δ + 19.9 (brs); HRMS

calcd for C₂₁H₂₄PO₃BSNa [M + Na]⁺, 421.1173; found, 421.1156.

(S)-Ferrocenyl[2-(methanesulfonatomethyl)phenyl]-

phenylphosphine-borane, 11d. The puriﬁcation was achieved by

chromatography on silica gel using dichloromethane as eluent: orange

solid; yield 78% (0.31 g); mp 156−158 °C; R_f0.49 (dichloro-

methane); [α]_D= +170.0 (c 0.2, CHCl₃); ¹H NMR (300 MHz,

CDCl₃) δ 2.71 (s, 3H), 4.06−4.08 (m, 1H), 4.09 (s, 5H), 4.53−4.55

(m, 1H), 4.63−4.66 (m, 1H), 4.75−4.78 (m, 1H), 4.98 (AB syst, J =

12.6 Hz, 1H), 5.27 (AB syst, J = 12.6 Hz), 7.10 (ddd, J = 1.1, 7.8, 11.8

(S)-[2-(Methanesulfonato-ethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane, 11f. To a solution of 2-(2-hydroxyethyl)-

phenylphosphine borane (10f) (0.28 g, 0.80 mmol) in dry CH₂Cl₂(6

mL) were added successively at 0 °C triethylamine (0.23 mL, 1.60

mmol) and methanesulfonyl chloride (0.10 mL, 1.3 mmol). The

reaction mixture was stirred to room temperature for 3 h, quenched

with water (10 mL), and extracted with dichloromethane (3 × 10 mL).

The combined organic phases were dried over MgSO₄, and the solvent

was removed under vacuum to give a residue, which was puriﬁed by

chromatography on silica gel using dichloromethane as eluent. White

sticky solid; yield 85% (0.29 g); R_f0.49 (dichloromethane); [α]_D

−3.8 (c 0.3, CHCl₃); H NMR (300 MHz, CDCl₃) δ 2.89 (s, 3H),

=

1

J

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3.13−3.19 (m, 2H), 3.56 (s, 3H), 4.27 (t, J = 7.6 Hz, 2H), 6.96 (ddd, J

= 0.5, 3.8, 8.3 Hz, 1H), 7.07 (tdd, J = 1.0, 2.1, 7.6 Hz, 1H), 7.13 (ddd, J

= 1.3, 7.9, 11.6 Hz, 1H), 7.22 (tt, J = 1.4, 7.8 Hz, 1H), 7.37−7.69 (m,

9H); ¹³C NMR (75.5 MHz, CDCl₃) δ 33.8 (d, J = 6.1 Hz), 37.1, 55.4,

70.2, 111.9 (d, J = 3.8 Hz), 117.0 (d, J = 57.7 Hz), 121.5 (d, J = 11.5

Hz), 126.8 (d, J = 9.1 Hz), 128.6 (d, J = 9.1 Hz), 129.0, 129.1 (d, J =

59.0 Hz), 130.9 (d, J = 3.0 Hz), 131.1 (d, J = 3.0 Hz), 131.5 (d, J = 9.1

Hz), 133.4 (d, J = 10.6 Hz), 134.0 (d, J = 7.6 Hz), 134.1 (d, J = 1.5

Hz), 135.4 (d, J = 10.6 Hz), 140.1 (d, J = 12.9 Hz), 161.5; ³¹P NMR

(121.5 MHz, CDCl₃) δ + 17.8 (brs); HRMS calcd for

C₂₂H₂₆PBSO₄Na [M + Na]⁺, 451.1279; found, 451.1266.

ether/dichloromethane, 1:1); 99% ee determined by HPLC analysis

on Lux 5 μm cellulose-2, 0.3 mL·min⁻¹, hexane/2-propanol, 99:1,

1

t_R(S) = 36.2 min, t_R(R) = 37.5 min; [α]_D+33.9 (c 0.3, CHCl₃); H

NMR (500 MHz, CDCl₃) δ 2.34 (s, 3H), 4.72 (AB syst, J = 11.2 Hz,

1H), 4.82 (AB syst, J = 11.2 Hz, 1H), 7.13 (d, J = 0.8, 7.0, 10.2 Hz,

1H), 7.18−7.33 (m, 4H), 7.45−7.64 (m, 7H), 7.72 (ddd, J = 0.8, 3.4,

6.9 Hz, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ 22.8, 32.1 (d, J = 5.0

Hz), 126.2 (d, J = 10.6 Hz), 127.1 (d, J = 55.9 Hz), 127.9 (d, J = 39.3

Hz), 128.2, 128.3 (d, J = 9.0 Hz), 128.9 (d, J = 10.6 Hz), 131.5 (d, J =

1.6 Hz), 131.7 (d, J = 1.6 Hz), 131.9, 132.1 (d, J = 8.8 Hz), 133.3 (d, J

= 7.8 Hz), 133.5 (d, J = 6.7 Hz), 133.9 (d, J = 9.2 Hz), 134.0 (d, J =

9.1 Hz), 142.3 (d, J = 9.8 Hz), 143.2 (d, J = 9.8 Hz); ³¹P NMR (202.5

MHz, CDCl₃) δ + 20.2 (brs); HRMS calcd for C₂₀H₂₁PBBrNa [M +

Na]⁺, 405.0553; found, 405.0543.

(S)-Ferrocenyl(2-bromomethylphenyl)phenylphosphine-borane,

11i. The puriﬁcation was achieved by chromatography using

dichloromethane as eluent. Orange solid; yield 78% (0.22 g); mp

166−168 °C; R_f0.73 (dichloromethane); 99% ee determined by

HPLC analysis on Chiralcel OD-H, 0.6 mL·min⁻¹, hexane/2-propanol,

98:2, t_R(R) = 12.8 min, t_R(S) = 14.6 min; [α]_D= +206.0 (c 0.2,

CHCl₃); ¹H NMR (500 MHz, CDCl₃) δ 4.08 (s, 5H), 4.13−4.15 (m,

1H), 4.51 (s, 2H), 4.53−4.55 (m, 1H), 4.62−4.63 (m, 1H), 4.75−4.77

(m, 1H), 7.06 (ddd, J = 1.2, 7.8, 11.7 Hz, 1H), 7.22 (tt, J = 1.4, 7.4 Hz,

1H), 7.45 (tt, J = 1.4, 7.7 Hz, 1H), 7.53−7.60 (m, 4H), 7.78−7.85 (m,

2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 31.8, 69.0 (d, J = 72.3 Hz),

69.9, 71.7 (d, J = 3.9 Hz), 72.2 (d, J = 10.5 Hz), 72.3 (d, J = 7.9 Hz),

74.6 (d, J = 14.5 Hz), 127.8 (d, J = 8.9 Hz), 129.0 (d, J = 11.8 Hz),

129.4 (d, J = 59.0 Hz), 130.9 (d, J = 51.7 Hz), 131.4 (d, J = 1.9 Hz),

131.6 (d, J = 2.5 Hz), 132.9 (d, J = 8.3 Hz), 133.0 (d, J = 7.1 Hz),

140.8 (d, J = 9.8 Hz); ³¹P NMR (202.5 MHz, CDCl₃) δ + 16.2 (brs);

HRMS calcd for C₂₃H₂₃PBBrFeNa [M + Na]⁺, 499.0061; found,

499.0076.

(R)-(2-Bromomethylphenyl)-(3,5-dimethylphenyl)-

phenylphosphine-borane, 11j. The puriﬁcation was achieved by

chromatography using a mixture of petroleum ether/dichloromethane

(2:1) as eluent. White solid; yield 70% (0.17 g); mp 136−138 °C; R_f

0.40 (petroleum ether/dichloromethane, 2:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 0.5 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(R) = 14.1 min, t_R(S) = 15.0 min; [α]_D+24.9 (c 0.3,

CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 2.35 (s, 6H), 4.63 (AB syst, J

= 11.2 Hz, 1H), 4.67 (AB syst, J = 11.2 Hz), 7.00 (ddd, J = 1.2, 7.8,

11.6 Hz, 1H), 7.19 (brs, 1H), 7.24−7.28 (m, 3H), 7.49−7.57 (m, 4H),

7.64−7.68 (m, 2H), 7.71 (ddd, J = 1.0, 4.1, 7.8 Hz, 1H); ¹³C NMR

(151 MHz, CDCl₃) δ 21.3, 32.0 (d, J = 5.7 Hz), 127.7 (d, J = 58.7 Hz),

128.1 (d, J = 6.2 Hz), 128.3 (d, J = 37.1 Hz), 128.6, 129.0 (d, J = 9.3

Hz), 130.9 (d, J = 9.3 Hz), 131.5 (d, J = 2.0 Hz), 131.8, 133.2 (d, J =

7.6 Hz), 133.5 (2d, J = 3.3 and J = 4.0 Hz), 134.0 (d, J = 7.6 Hz),

138.7 (d, J = 12.4 Hz), 142.1 (d, J = 9.3 Hz); ³¹P NMR (243 MHz,

CDCl₃) δ + 20.1 (brs); HRMS calcd for C₂₁H₂₃PBBrNa [M + Na]⁺,

419.0710; found, 419.0709.

Synthesis of Phosphine-borane-sulﬁdes 12. General Proce-

dure. To a solution of thiol (0.42 mmol) in dry THF (1 mL) was

added at 0 °C 0.2 mL of n-BuLi (2.5 M in hexane, 0.50 mmol). The

resulting solution was stirred 20 min at 0 °C then 20 min at room

temperature and added to a solution of mesylates 11a−f (0.21 mmol)

or bromides 11g−j (0.21 mmol) in dry THF (3 mL). After stirring for

20 min at room temperature, the reaction mixture was quenched with

water (5 mL) and extracted with dichloromethane (3 × 10 mL). The

combined organic phases were dried over MgSO₄, and the solvent was

removed under vacuum to give a residue, which was puriﬁed by

chromatography on silica gel.

Synthesis of (2-Bromomethylphenyl)phosphine-boranes,

11g−j. Method B: General Procedure from 2-(Hydroxymethyl)-

phenylphosphine-borane, 10. To

a solution of (2-

hydroxymethylphenyl)phosphine-borane 10 (0.6 mmol) in dichloro-

methane (4 mL) were successively added carbon tetrabromide (1.10

mmol) and triphenylphosphine (1.20 mmol). After stirring 2 h at

room temperature, the solvent was removed and the residue puriﬁed

by chromatography on silica gel.

( S ) - ( 2 - B r o m o m e t h y l p h e n y l ) - ( 2 - m e t h o x y p h e n y l ) -

phenylphosphine-borane, 11g: white sticky solid; yield 67% (0.16 g);

99% ee determined by HPLC analysis on Lux 5 μm cellulose-2, 0.5

mL·min⁻¹, hexane/2-propanol, 98:2, t_R(S) = 26.4 min, t_R(R) = 27.9

min. All of the analyses are similar to those described below.

(R)-(2-Bromomethylphenyl)-(2-methylphenyl)phenylphosphine-

borane, 11h: white sticky solid; yield 58% (0.14 g); R_f0.58

(petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 0.3 mL·min⁻¹, hexane/2-

propanol, 99:1, t_R(S) = 36.2 min, t_R(R) = 37.5 min. All of the analyses

are similar to those described below.

(S)-(2-Bromomethylphenyl)ferrocenylphenylphosphine-borane,

11i: orange solid; yield 75% (0.21 g); R_f0.73 (dichloromethane); 99%

ee determined by HPLC analysis on Chiralcel OD-H, 0.6 mL·min⁻¹,

hexane/2-propanol, 98:2, t_R(R) = 12.8 min, t_R(S) = 14.6 min. All of

the analyses are similar to those described below.

(R)-(2-Bromomethylphenyl)-(3,5-dimethylphenyl)-

phenylphosphine-borane, 11j: white solid; yield 72% (0.17 g); R_f

0.40 (petroleum ether/dichloromethane, 2:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 0.5 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(R) = 14.1 min, t_R(S) = 15.0 min. All of the analyses

are similar to those described below.

Method C: General Procedure from Mesylates 11. To a

solution of mesylate 11 (0.60 mmol) in dimethylacetamide (4 mL)

was added sodium bromide (1.80 mmol). The reaction mixture was

stirred 3 h, quenched with water (5 mL), and extracted with

dichloromethane (3 × 10 mL). The combined organic phases were

dried over MgSO₄, and the solvent was removed under vacuum to give

a residue, which was puriﬁed by chromatography on silica gel.

( S)-(2-Bro momet hyl phenyl)-(2-methoxylphenyl)-

phenylphosphine-borane, 11g. The puriﬁcation was achieved by

chromatography on silia gel using dichloromethane as eluent. White

sticky solid; yield 65% (0.16 g); R_f0.69 (dichloromethane); 99% ee

determined by HPLC analysis on Lux 5 μm cellulose-2, 0.5 mL·min⁻¹,

hexane/2-propanol, 98:2, t_R(S) = 26.4 min, t_R(R) = 27.9 min; [α]_D=

1

−51.7 (c 0.4, CHCl₃); H NMR (500 MHz, CDCl₃) δ 3.54 (s, 3H),

4.62 (AB syst, J = 10.3 Hz, 1H), 4.71 (AB syst, J = 10.3 Hz, 1H), 6.96

(dd, J = 3.7, 7.8 Hz, 1H), 7.10−7.16 (m, 2H), 7.24 (tt, J = 1.4, 7.6 Hz,

1H), 7.46−7.59 (m, 5H), 7.63 (ddd, J = 1.0, 4.4, 7.7 Hz, 1H), 7.74−

7.78 (m, 2H), 7.81 (ddd, J = 1.7, 7.7, 13.7 Hz, 1H); ¹³C NMR (125.8

MHz, CDCl₃) δ 32.2 (d, J = 6.2 Hz), 55.3, 112.0 (d, J = 3.7 Hz), 116.1

(d, J = 55.9 Hz), 121.6 (d, J = 11.2 Hz), 127.8 (d, J = 9.1 Hz), 128.2

(d, J = 60.1 Hz), 128.5 (d, J = 10.4 Hz), 129.0 (d, J = 56.8 Hz), 131.0

(d, J = 1.7 Hz), 131.2 (d, J = 2.5 Hz), 132.8 (d, J = 5.0 Hz), 132.9 (d, J

= 5.0 Hz), 133.7 (d, J = 10.0 Hz), 134.2 (d, J = 2.0 Hz), 135.6 (d, J =

13.0 Hz), 141.1 (d, J = 9.7 Hz), 161.6; ³¹P NMR (202.5 MHz, CDCl₃)

δ + 17.4 (brs); HRMS calcd for C₂₀H₂₁POBBrNa [M + Na]⁺,

421.0502; found, 421.0499.

(S)-(2-Methoxyphenyl)phenyl[2-(phenylthiomethyl)phenyl]-

phosphine-borane, 12a. The puriﬁcation was achieved by chroma-

tography on silica gel using a mixture of petroleum ether/

dichloromethane (2:1) as eluent. Colorless, sticky solid; yield 56%

(0.050 g); R_f0.32 (petroleum ether/dichloromethane, 2:1); 99% ee

determined by HPLC analysis on chiralpak IB, 0.5 mL·min⁻¹, hexane/

2-propanol, 99:1, t_R(S) = 25.2 min, t_R(R) = 26.2 min; [α]_D= −33.1 (c

(R)-(2-Bromomethylphenyl)-(2-methylphenyl)phenylphosphine-

borane, 11h. The puriﬁcation was achieved by chromatography on

silica gel using a mixture of petroleum ether/dichloromethane (1:1) as

eluent. White sticky solid; yield 47% (0.11 g); R_f0.58 (petroleum

1

0.3, CHCl₃); H NMR (500 MHz, CDCl₃) δ 3.56 (s, 3H), 4.27 (AB

syst, J = 13.8 Hz, 1H), 4.34 (AB syst, J = 13.8 Hz, 1H), 6.94 (ddd, J =

K

DOI: 10.1021/acs.organomet.5b00585

Organometallics XXXX, XXX, XXX−XXX

Organometallics

Article

0.4, 3.7, 8.2 Hz, 1H), 7.05−7.07 (m, 3H), 7.13−7.22 (m, 5H), 7.40−

7.52 (m, 5H), 7.59−7.61 (m, 1H), 7.75−7.80 (m, 3H); ¹³C NMR

(125.8 MHz, CDCl₃) δ 37.3 (d, J = 5.6 Hz), 55.3, 111.9 (d, J = 5.3

Hz), 116.7 (d, J = 56.5 Hz), 121.5 (d, J = 10.6 Hz), 125.9, 126.8 (d, J =

9.5 Hz), 128.5, 128.6, 128.7, 128.8 (d, J = 59.6 Hz), 129.0, 130.6 (d, J

= 9.1 Hz), 130.8 (d, J = 2.5 Hz), 131.1 (d, J = 2.1 Hz), 133.3 (d, J =

7.6 Hz), 133.7 (d, J = 10.6 Hz), 134.0 (d, J = 1.5 Hz), 135.5 (d, J =

13.6 Hz), 136.6, 140.7 (d, J = 9.7 Hz), 161.6; ³¹P NMR (202.5 MHz,

CDCl₃) δ + 17.8 (brs); HRMS calcd for C₂₆H₂₆POSBNa [M + Na]⁺,

451.1432; found, 451.1423.

(R)-(2-Methylphenyl)phenyl[2-(phenylthiomethyl)phenyl]-

phosphine-borane, 12b. The puriﬁcation was achieved by chroma-

tography on silica gel using a mixture of petroleum ether/

dichloromethane (2:1) as eluent. Colorless, sticky solid; yield 54%

(0.047 g); R_f0.28 (petroleum ether/dichloromethane, 2:1); 99% ee by

HPLC analysis on chiralpak IB, 0.5 mL·min⁻¹, hexane/2-propanol,

98:2, t_R(S) = 13.8 min, t_R(R) = 14.5 min; [α]_D= +47.8 (c 0.2, CHCl₃);

¹H NMR (500 MHz, CDCl₃) δ 2.36 (s, 3H), 4.35 (AB syst, J = 13.8

Hz), 4.45 (AB syst, J = 13.8 Hz), 7.11−7.26 (m, 9H), 7.31 (dd, J = 4.1,

7.8 Hz), 7.40−7.56 (m, 5H), 7.60−7.64 (m, 2H), 7.68 (dd, J = 4.1, 7.8

Hz, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ 22.8, 37.6 (d, J = 5.0 Hz),

126.0, 126.2 (d, J = 9.5 Hz), 127.3 (d, J = 8.2 Hz), 127.6 (d, J = 50.3

Hz), 128.2, 128.7, 128.9 (d, J = 9.5 Hz), 129.3, 131.0 (d, J = 8.2 Hz),

131.4, 131.5, 132.0 (d, J = 9.5 Hz), 133.7, 133.8, 133.9 (d, J = 9.3 Hz),

136.3, 142.0 (d, J = 5.9 Hz), 143.1 (d, J = 11.8 Hz); ³¹P NMR (202.5

MHz, CDCl₃) δ + 20.3 (brs); HRMS calcd for C₂₆H₂₆PSBNa [M +

Na]⁺, 435.1483; found, 435.1464.

After stirring 30 min at room temperature, the solution was quenched

with water (5 mL) and extracted with dichloromethane (3 × 10 mL).

The combined organic phases were dried over MgSO₄, and the solvent

was removed under vacuum to give a residue, which was puriﬁed by

chromatography on silica gel using petroleum ether/dichloromethane

(1:1) as eluent. White sticky solid; yield 32% (0.069 g); R_f0.31

(petroleum ether/dichloromethane, 1:1); 99% ee by HPLC analysis

on Lux 5 μm cellulose-1, 1.0 mL·min⁻¹, hexane/2-propanol, 98:2,

1

t_R(S) = 21.7 min, t_R(R) = 24.3 min; [α]_D= −1.6 (c 0.3, CHCl₃); H

NMR (500 MHz, CDCl₃) δ 2.85−2.95 (m, 2H), 2.99−3.03 (m, 2H),

3.56 (s, 3H), 6.93 (dd, J = 3.8, 8.2 Hz, 1H), 7.05 (ddd, J = 0.9, 1.9, 7.6

Hz, 1H), 7.16−7.27 (m, 7H), 7.33 (dd, J = 4.3, 7.9 Hz, 1H), 7.41−

7.54 (m, 5H), 7.60 (ddd, J = 1.8, 7.7, 13.0 Hz, 1H), 7.65−7.69 (m,

2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 34.2 (d, J = 5.8 Hz), 34.6,

55.4, 111.8 (d, J = 3.8 Hz), 117.4 (d, J = 56.8 Hz), 121.5 (d, J = 11.4

Hz), 125.8, 126.2 (d, J = 9.9 Hz), 128.1 (d, J = 57.2 Hz), 128.4 (d, J =

9.9 Hz), 128.8, 129.3, 129.4 (d, J = 59.2 Hz), 130.7−130.9 (m), 133.4

(d, J = 9.9 Hz), 133.8 (d, J = 1.7 Hz), 133.9 (d, J = 8.5 Hz), 135.4 (d, J

= 11.4 Hz), 136.5, 144.3 (d, J = 9.1 Hz), 161.4; ³¹P NMR (202.5 MHz,

CDCl₃) δ + 18.2 (brs); HRMS calcd for C₂₇H₂₈PBSONa [M + Na]⁺,

465.1589; found, 465.1574.

(S)-[2-(Ethylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane 12g. The puriﬁcation was achieved by

chromatography on silica gel using petroleum ether/dichloromethane

(1:1) as eluent. White oil; yield 70% (0.056 g); R_f0.46 (petroleum

ether/dichloromethane, 1:1); 99% ee determined by HPLC analysis

on Lux 5 μm cellulose-1, 0.5 mL·min⁻¹, hexane/2-propanol, 98:2,

t_R(S) = 16.0 min, t_R(R) = 16.9 min; [α]_D= −17.9 (c 0.3, CHCl₃); ¹H

NMR (500 MHz, CDCl₃) δ 1.05 (t, J = 7.5 Hz, 3H), 2.27 (qd, J = 1.4,

7.5 Hz, 2H), 3.55 (s, 3H), 3.84 (AB syst, J = 14.1 Hz, 1H), 3.88 (AB

syst, J = 14.1 Hz, 1H), 6.94 (dd, J = 3.7, 8.1 Hz, 1H), 7.08−7.19 (m,

3H), 7.44−7.55 (m, 5H), 7.73−7.77 (m, 4H); ¹³C NMR (125.8 MHz,

CDCl₃) δ 14.3, 26.5, 35.2 (d, J = 6.0 Hz), 55.3, 111.8 (d, J = 4.7 Hz),

117.0 (d, J = 55.8 Hz), 121.3 (d, J = 11.6 Hz), 126.5 (d, J = 9.7 Hz),

128.2, 128.5 (d, J = 9.7 Hz), 128.7 (d, J = 9.7 Hz), 129.2, 130.5 (d, J =

8.7 Hz), 130.7 (d, J = 2.2 Hz), 131.0 (d, = 2.6 Hz), 133.2 (d, J = 7.5

Hz), 133.6, 133.7, 133.9 (d, J = 1.9 Hz), 135.5 (d, J = 13.0 Hz), 142.2

(d, J = 12.1 Hz), 161.6; ³¹P NMR (202.5 MHz, CDCl₃) δ + 17.6 (brs);

HRMS calcd for C₂₂H₂₆POSNa [M + Na]⁺, 403.1416; found,

403.1431.

(S)-Ferrocenylphenyl[2-(phenylthiomethyl)phenyl]phosphine-

borane, 12d. The puriﬁcation was achieved by chromatography on

silica gel using a mixture of petroleum ether/dichloromethane (2:1) as

eluent. Orange sticky solid; yield 84% (0.089 g); R_f0.31 (petroleum

ether/dichloromethane, 2:1); 99% ee determined by HPLC analysis

on Chiralcel OD-H, 0.5 mL·min⁻¹, hexane/2-propanol, 90:10, t_R(R) =

1

13.4 min, t_R(S) = 15.5 min; [α]_D= +129.4 (c 0.3, CHCl₃); H NMR

(500 MHz, CDCl₃) δ 3.96 (d, J = 14.3 Hz, 1H), 4.08 (s, 5H), 4.13−

4.14 (m, 1H), 4.32 (d, J = 14.3 Hz, 1H), 4.52−4.54 (m, 1H), 4.61−

4.62 (m, 1H), 4.78−4.80 (m, 1H), 7.02−7.04 (m, 2H), 7.09−7.14 (m,

2H), 7.17−7.21 (m, 3H), 7.38 (tt, J = 1.4, 7.5 Hz, 1H), 7.49−7.59 (m,

4H), 7.81−7.85 (m, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 37.0 (d, J

= 5.2 Hz), 69.6 (d, J = 70.3 Hz), 69.9, 71.7 (d, J = 3.6 Hz), 72.0 (d, J =

8.5 Hz), 72.2 (d, J = 6.1 Hz), 74.7 (d, J = 15.8 Hz), 125.8, 126.8 (d, J =

8.6 Hz), 128.7, 128.8 (d, J = 7.1 Hz), 129.9 (d, J = 58.7 Hz), 130.4 (d,

J = 7.9 Hz), 130.7, 131.1 (2s), 131.5 (d, J = 2.1 Hz), 132.9 (d, J = 8.6

Hz), 133.3 (d, J = 8.6 Hz), 136.6, 140.1 (d, J = 8.6 Hz); ³¹P NMR

(202.5 MHz, CDCl₃) δ + 16.2 (brs); HRMS calcd for

C₂₉H₂₈PSBFeNa [M + Na]⁺, 529.0989; found, 529.0983.

(R)-(3,5-Dimethylphenyl)phenyl[2-(phenylthiomethyl)phenyl]-

phosphine-borane, 12e. The puriﬁcation was achieved by chroma-

tography on silica gel using a mixture of petroleum ether/

dichloromethane (2:1) as eluent. White sticky solid; yield 78%

(0.070 g); R_f0.29 (petroleum ether/dichloromethane, 2:1); 99% ee

determined by HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹,

hexane/2-propanol, 98:2, t_R(R) = 8.6 min, t_R(S) = 9.8 min; [α]_D+20.0

(c 0.3, CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 2.33 (s, 6H), 4.28 (AB

syst, J = 14.4 Hz), 4.31 (AB syst, J = 14.4 Hz), 7.04−7.08 (m, 3H),

7.14−7.15 (m, 2H), 7.18−7.25 (m, 3H), 7.26 (brs, 1H), 7.28 (brs,

1H), 7.45−7.55 (m, 4H), 7.65−7.69 (m, 3H); ¹³C NMR (151 MHz,

CDCl₃) δ 21.3, 37.3 (d, J = 5.3 Hz), 125.9, 127.1 (d, J = 8.7 Hz), 128.0

(d, J = 45.4 Hz), 128.4 (d, J = 43.6 Hz), 128.7, 128.8 (d, J = 10.0 Hz),

128.9, 129.2, 130.8 (d, J = 9.6 Hz), 130.9 (d, J = 8.4 Hz), 131.3 (d, J =

2.0 Hz), 131.5 (d, J = 1.8 Hz), 133.3 (d, J = 2.2 Hz), 133.5 (d, J = 9.2

Hz), 134.3 (d, J = 7.9 Hz), 136.5, 138.7 (d, J = 11.7 Hz), 141.7 (d, J =

11.7 Hz); ³¹P NMR (243 MHz, CDCl₃) δ + 19.4 (brs); HRMS calcd

for C₂₇H₂₅PSNa [M − BH₃+ Na]⁺, 435.1307; found, 435.1299.

(S)-(2-Methoxyphenyl)phenyl[2-(phenylthioethyl)phenyl]-

phosphine-borane, 12f. To a solution of thiophenol (0.10 mL, 0.97

mmol) in dry THF (2 mL) was added at 0 °C n-BuLi (2.5 M in

hexane) (0.47 mL, 1.16 mmol). The resulting solution was stirred 20

min at 0 °C and 20 min at room temperature and then added to a

solution of mesylate 11f (0.21 g, 0.49 mmol) in dry THF (5 mL).

(S)-[2-(tert-Butylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane, 12h. The puriﬁcation was achieved by

chromatography on silica gel using petroleum ether/dichloromethane

(2:1) as eluent. Colorless, sticky solid; yield 73% (0.063 g); R_f0.23

(petroleum ether/dichloromethane, 2:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 0.5 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 15.5 min, t_R(R) = 16.5 min; [α]_D= −3.3 (c 0.3,

1

CHCl₃); H NMR (600 MHz, CDCl₃) δ 1.12 (s, 9H), 3.55 (s, 3H),

3.85 (AB syst, J = 13.2 Hz, 1H), 3.93 (AB syst, J = 13.2 Hz, 1H), 6.95

(dd, J = 3.7, 7.9 Hz, 1H), 7.08−7.13 (m, 2H), 7.17 (tt, J = 1.4, 7.5 Hz,

1H), 7.42−7.55 (m, 5H), 7.69 (ddd, J = 0.6, 4.4, 7.7 Hz, 1H), 7.76−

7.80 (m, 3H); ¹³C NMR (151 MHz, CDCl₃) δ 30.6, 32.1 (d, J = 7.7

Hz), 42.5, 55.3, 111.9 (d, J = 5.0 Hz), 117.1 (d, J = 56.9 Hz), 121.4 (d,

J = 12.4 Hz), 126.4 (d, J = 8.6 Hz), 128.4 (d, J = 10.6 Hz), 128.8,

129.2, 130.6 (d, J = 1.8 Hz), 131.0 (d, J = 2.1 Hz), 131.1 (d, J = 8.7

Hz), 132.9 (d, J = 7.8 Hz), 133.8, 133.8 (d, J = 9.7 Hz), 135.6 (d, J =

12.9 Hz), 141.7 (d, J = 13.5 Hz), 161.7; ³¹P NMR (243 MHz, CDCl₃)

δ + 17.4 (brs); HRMS calcd for C₂₄H₂₇POSNa [M − BH₃+ Na]⁺,

417.1412; found, 417.1409.

(S)-[2-(Benzylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane, 12i. The puriﬁcation was achieved by

chromatography on silica gel using petroleum ether/dichloromethane

(1:1) as eluent. White, sticky solid; yield 58% (0.054 g); R_f0.48

(petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-1, 0.5 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 26.8 min, t_R(R) = 28.1 min; [α]_D= −1.6 (c 0.3,

1

CHCl₃); H NMR (500 MHz, CDCl₃) δ 3.43 (s, 2H), 3.54 (s, 3H),

3.80 (AB syst, J = 13.7 Hz, 1H), 3.85 (AB syst, J = 13.7 Hz, 1H), 6.94

(dd, J = 3.7, 8.2 Hz, 1H), 7.08−7.28 (m, 8H), 7.40−7.58 (m, 6H),

7.73−7.77 (m, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 35.6 (d, J = 5.5

L

DOI: 10.1021/acs.organomet.5b00585

Organometallics XXXX, XXX, XXX−XXX

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Hz), 37.2, 55.3, 111.8 (d, J = 4.1 Hz), 117.0 (d, J = 55.9 Hz), 121.4 (d,

J = 12.4 Hz), 126.6 (d, J = 9.7 Hz), 126.8, 128.4, 128.5, 128.5 (d, J =

52.9 Hz), 128.8, 129.0 (d, J = 54.7 Hz), 130.7 (d, J = 8.8 Hz), 130.8 (d,

J = 2.7 Hz), 131.0 (d, J = 2.7 Hz), 133.2 (d, J = 8.0 Hz), 133.7 (d, J =

9.4 Hz), 133.9 (d, J = 1.6 Hz), 135.5 (d, J = 12.1 Hz), 138.1, 141.8 (d,

J = 9.0 Hz), 161.5; ³¹P NMR (202.5 MHz, CDCl₃) δ + 17.8 (brs);

HRMS calcd for C₂₇H₂₈POSBNa [M + Na]⁺, 465.1589; found,

465.1584.

mixture of petroleum ether/dichloromethane (1:1) as eluent.

Colorless, sticky solid; yield 42% (0.045 g); R_f0.53 (petroleum

ether/dichloromethane, 1:1); 99% ee determined by HPLC analysis

on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-propanol, 95:5,

1

t_R(R) = 5.0 min, t_R(S) = 5.5 min; [α]_D= −9.7 (c 0.2, CHCl₃); H

NMR (500 MHz, CDCl₃) δ 1.00−1.01 (2s, 18H), 1.09−1.14 (m, 3H),

3.55 (s, 3H), 3.85 (AB syst, J = 14.2 Hz, 1H), 3.88 (AB syst, J = 14.2

Hz, 1H), 6.94 (dd, J = 3.8, 8.3 Hz, 1H), 7.07−7.11 (m, 2H), 7.17 (t, J

= 7.7 Hz, 1H), 7.43−7.55 (m, 5H), 7.74−7.79 (m, 3H), 7.92 (dd, J =

4.2, 7.7 Hz, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ 12.5, 18.5, 29.1 (d,

J = 6.1 Hz), 55.3, 111.8 (d, J = 3.6 Hz), 117.1 (d, J = 56.4 Hz), 121.4

(d, J = 10.9 Hz), 126.3 (d, J = 9.3 Hz), 128.1 (d, J = 57.7 Hz), 128.4

(d, J = 9.3 Hz), 129.0 (d, J = 59.6 Hz), 130.5 (d, J = 8.0 Hz), 130.8 (d,

J = 1.7 Hz), 130.9 (d, J = 2.4 Hz), 132.7 (d, J = 7.5 Hz), 133.6 (d, J =

9.5 Hz), 133.8, 135.6 (d, J = 12.0 Hz), 143.8 (d, J = 9.9 Hz), 161.5; ³¹P

NMR (202.5 MHz, CDCl₃) δ + 17.7 (brs); HRMS calcd for

C₂₉H₄₂POSBSiNa [M + Na]⁺, 531.2454; found, 531.2431.

(S)-[2-(4-Methoxyphenylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane 12j. The puriﬁcation was achieved by

chromatography on silica gel using a mixture of petroleum ether/

dichloromethane (1:1) as eluent. Colorless, sticky solid; yield 63%

(0.061 g); R_f0.36 (petroleum ether/dichloromethane, 1:1); 99% ee

determined by HPLC analysis on Lux 5 μm cellulose-1, 0.5 mL·min⁻¹,

hexane/2-propanol, 98:2, t_R(S) = 24.3 min, t_R(R) = 25.7 min; [α]_D=

1

−41.0 (c 0.2, CHCl₃); H NMR (500 MHz, CDCl₃) δ 3.56 (s, 3H),

3.79 (s, 3H), 4.19 (AB syst, J = 13.5 Hz), 4.26 (AB syst, J = 13.5 Hz,

1H), 6.75 (d, J = 8.9 Hz, 2H), 6.95 (dd, J = 3.8, 7.8 Hz, 1H), 7.04−

7.09 (m, 3H), 7.17−7.20 (m, 2H), 7.38−7.55 (m, 6H), 7.74−7.78 (m,

3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 39.5 (d, J = 5.6 Hz), 55.3 (2s),

111.9 (d, J = 4.6 Hz), 114.4, 117.0 (d, J = 55.7 Hz), 121.4 (d, J = 12.0

Hz), 126.6, 126.8 (d, J = 8.6 Hz), 128.4 (d, J = 10.3 Hz), 128.5 (d, J =

41.0 Hz), 128.9 (d, J = 42.7 Hz), 130.6 (d, J = 2.4 Hz), 130.9 (d, J =

8.6 Hz), 131.0 (d, J = 2.4 Hz), 133.1, 133.3 (d, J = 8.0 Hz), 133.7 (d, J

= 9.5 Hz), 133.9, 135.5 (d, J = 12.7 Hz), 141.2 (d, J = 11.3 Hz), 158.9,

161.6; ³¹P NMR (202.5 MHz, CDCl₃) δ + 17.6 (brs); HRMS calcd for

C₂₇H₂₈PO₂SBNa [M + Na]⁺, 481.1538; found, 481.1541.

Preparation of Phosphine-Sulﬁdes 13. Method A: General

Procedure from Phosphine-borane-sulﬁdes 12a−p. To a solution of

phosphine-borane-sulﬁdes 12a−p (0.30 mmol) in toluene (2 mL) was

added DABCO (0.90 mmol). The reaction mixture was stirred for 2 h

at room temperature, and the solvent was removed under vacuum to

give a residue, which was puriﬁed by chromatography on a column.

(S)-(2-Methoxyphenyl)phenyl[2-(phenylthiomethyl)phenyl]-

phosphine, 13a. The puriﬁcation was accomplished by chromatog-

raphy on silica gel using a mixture of petroleum ether/dichloro-

methane (2:1) as eluent. Colorless oil; yield 84% (0.104 g); R_f0.36

(petroleum ether/dichloromethane, 2:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-1, 1.0 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 7.2 min, t_R(R) = 8.0 min; [α]_D= +7.1 (c 0.3,

(S)-[2-(3,5-Dimethylphenylthiomethyl)phenyl]-(2-

methoxyphenyl)phenylphosphine-borane, 12l. The puriﬁcation was

achieved by chromatography on silica gel using a mixture of petroleum

ether/dichloromethane (1:1) as eluent. White solid; yield 45% (0.043

g); mp 46−48 °C; R_f0.49 (petroleum ether/dichloromethane, 1:1);

99% ee determined by HPLC analysis on Lux 5 μm cellulose-2, 1.0

mL·min⁻¹, hexane/2-propanol, 99:1, t_R(S) = 41.9 min, t_R(R) = 45.9

1

CHCl₃); H NMR (500 MHz, CDCl₃) δ 3.76 (s, 3H), 4.48 (s, 2H),

6.70−7.72 (m, 1H), 6.88−6.94 (m, 3H), 7.13−7.39 (m, 13H), 7.48−

7.50 (m, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ 37.1 (d, J = 27.7 Hz),

55.7, 110.3, 121.1, 125.1 (d, J = 11.7 Hz), 125.8, 127.3, 128.4 (d, J =

7.0 Hz), 128.6, 128.7, 129.0, 129.3 (2s), 130.4, 133.8, 134.0, 134.1 (d, J

= 10.7 Hz), 135.9 (d, J = 13.0 Hz), 136.1 (d, J = 9.6 Hz), 136.8, 141.7

(d, J = 23.4 Hz, 161.2 (d, J = 11.7 Hz); ³¹P NMR (202.5 MHz,

CDCl₃) δ −27.4 (s); HRMS calcd for C₂₆H₂₃POSNa [M + Na]⁺,

437.1099; found, 437.1097.

1

min; [α]_D= −21.0 (c 0.2, CHCl₃); H NMR (600 MHz, CDCl₃) δ

2.26 (s, 6H), 3.58 (s, 3H), 4.25 (AB syst, J = 13.6 Hz, 1H), 4.31 (AB

syst, J = 13.6 Hz, 1H), 6.71 (s, 2H), 6.78 (s, 1H), 6.97 (dd, J = 3.6, 8.4

Hz, 1H), 7.06−7.09 (m, 1H), 7.18−7.22 (m, 2H), 7.42−7.55 (m, 5H),

7.63 (dd, J = 4.6, 7.5 Hz, 1H), 7.79−7.83 (m, 3H); ¹³C NMR (151

MHz, CDCl₃) δ 21.2, 37.4 (d, J = 5.4 Hz), 55.3, 111.9 (d, J = 4.0 Hz),

116.9 (d, J = 57.3 Hz), 121.4 (d, J = 12.1 Hz), 126.8−126.9 (m),

127.9, 128.5 (d, J = 10.8 Hz), 128.7, 129.0 (d, J = 22.2 Hz), 130.7,

130.8 (d, J = 10.0 Hz), 131.0 (d, J = 2.5 Hz), 133.2 (d, J = 8.3 Hz),

133.7 (d, J = 9.1 Hz), 134.0, 135.5 (d, J = 14.2 Hz), 136.1, 138.2, 140.9

(d, J = 10.6 Hz), 161.6; ³¹P NMR (243 MHz, CDCl₃) δ + 17.6 (brs);

HRMS calcd for C₂₈H₃₀POSBNa [M + Na]⁺, 479.1729; found,

479.1745.

(R)-(2-Methylphenyl)phenyl[2-(phenylthiomethyl)phenyl]-

phosphine, 13b. The puriﬁcation was achieved by chromatography on

silica gel using a mixture of petroleum ether/dichloromethane (2:1) as

eluent. Colorless oil; yield 93% (0.111 g); R_f0.41 (petroleum ether/

dichloromethane, 2:1); 99% ee by HPLC analysis on Lux 5 μm

cellulose-1, 0.5 mL·min⁻¹, hexane/2-propanol, 99:1, t_R(S) = 16.7 min,

1

t_R(R) = 18.0 min; [α]_D= +6.1 (c 0.3, CHCl₃); H NMR (600 MHz,

CD₂Cl₂) δ 2.40 (s, 3H), 4.42 (ABX syst, J = 1.9, 13.5 Hz, 1H), 4.47

(ABX syst, J = 1.9, 13.5 Hz), 6.81 (ddd, J = 1.0, 4.2, 7.5 Hz, 1H), 6.92

(ddd, J = 1.2, 4.2, 7.7 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.18−7.21 (m,

2H), 7.25−7.34 (m, 9H), 7.39−7.42 (m, 3H), 7.49 (ddd, J = 0.8, 4.8,

7.7 Hz, 1H); ¹³C NMR (151 MHz, CD₂Cl₂) δ 20.9 (d, J = 22.3 Hz),

37.2 (d, J = 26.0 Hz), 126.0 (d, J = 10.3 Hz), 127.5, 128.6 (d, J = 7.2

Hz), 128.7, 128.8, 129.0, 129.4, 129.5 (d, J = 4.1 Hz), 130.1 (d, J = 5.2

Hz), 132.9, 134.1, 134.2, 135.5 (d, J = 7.2 Hz), 135.6 (d, J = 10.1 Hz),

135.8 (d, J = 10.1 Hz), 136.6, 141.9 (d, J = 26.0 Hz), 142.2 (d, J = 26.0

Hz); ³¹P NMR (243 MHz, CD₂Cl₂) δ −24.5 (s); HRMS calcd for

C₂₆H₂₃PSNa [M + Na]⁺, 421.1150; found, 421.1136.

(S)-[2-(4-Triﬂuoromethylphenylthiomethyl)phenyl]-(2-

methoxyphenyl)phenylphosphine-borane, 12n. The puriﬁcation was

achieved by chromatography using a mixture of petroleum ether/

dichloromethane (2:1) as eluent. Colorless oil; yield 56% (0.058 g); R_f

0.24 (petroleum ether/dichloromethane, 2:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 90:10, t_R(S) = 5.9 min, t_R(R) = 6.4 min; [α]_D= −48.0 (c 0.2,

CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 3.57 (s, 3H), 4.35 (AB syst, J

= 13.9 Hz, 1H), 4.40 (AB syst, J = 13.9 Hz, 1H), 6.93−6.95 (m, 1H),

7.00−7.04 (m, 1H), 7.08−7.10 (m, 2H), 7.16−7.25 (m, 2H), 7.40−

7.54 (m, 7H), 7.61−7.63 (m, 1H), 7.72−7.79 (m, 2H); ¹³C NMR

(151 MHz, CDCl₃) δ 36.0 (d, J = 5.7 Hz), 55.3, 111.8 (d, J = 4.3 Hz),

116.3, 116.8, 121.2, 121.5 (d, J = 11.8 Hz), 123.1, 125.2, 125.4 (q, J =

3.6 Hz), 127.1, 127.2, 127.4, 128.5 (d, J = 10.2 Hz), 128.8 (q, J = 59.5

Hz), 130.4 (d, J = 33.2 Hz), 130.9 (d, J = 2.2 Hz), 131.2 (d, J = 2.2

Hz), 133.4 (d, J = 7.2 Hz), 133.7 (2s), 134.1, 135.6 (d, J = 12.9 Hz),

139.5 (d, J = 10.8 Hz), 142.2, 161.5; ³¹P NMR (243 MHz, CDCl₃) δ +

17.6 (brs); HRMS calcd for C₂₇H₂₅F₃POSBNa [M + Na]⁺, 519.1306;

found, 519.1291.

(S)-Ferrocenylphenyl[2-(phenylthiomethyl)phenyl]phosphine,

13d. The puriﬁcation was achieved by chromatography on silica gel

using a mixture of petroleum ether/dichloromethane (2:1) as eluent.

Orange oil; yield 91% (0.134 g); R_f0.45 (petroleum ether/

dichloromethane, 2:1); 99% ee determined by HPLC analysis on

Chiralcel OD-H, 0.5 mL·min⁻¹, hexane/2-propanol, 90:10, t_R(R) =

1

10.2 min, t_R(S) = 11.4 min; [α]_D= +137.5 (c 0.3, CHCl₃); H NMR

(500 MHz, CDCl₃) δ 3.89−3.90 (m, 1H), 4.12 (s, 5H), 4.25 (dd, J =

2.2, 13.5 Hz, 1H), 4.34−4.35 (m, 1H), 4.38−4.43 (m, 2H), 4.44−4.45

(m, 1H), 7.07 (ddd, J = 1.3, 4.2, 7.6 Hz, 1H), 7.15−7.18 (m, 2H),

7.21−7.25 (m, 5H), 7.36−7.38 (m, 4H), 7.46−7.50 (m, 2H); ¹³C

NMR (125.8 MHz, CDCl₃) δ 37.1 (d, J = 24.9 Hz), 69.2, 70.5, 71.2 (d,

J = 6.9 Hz), 72.2 (d, J = 3.5 Hz), 74.1 (d, J = 26.0 Hz), 75.6 (d, J = 5.2

(S)-[2-(Tri-isopropylsilylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine-borane, 12o. The general procedure was followed

except that the reaction mixture was stirred 1 h at room temperature.

The puriﬁcation was achieved by chromatography on silica gel using a

M

DOI: 10.1021/acs.organomet.5b00585

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Hz), 125.9, 127.0, 128.2 (d, J = 7.8 Hz), 128.6, 128.7, 128.8, 129.2 (d, J

= 4.3 Hz), 129.3, 133.2, 134.0 (d, J = 18.3 Hz), 136.8, 137.4 (d, J = 8.1

Hz), 138.8 (d, J = 12.2 Hz), 140.2 (d, J = 22.4 Hz); ³¹P NMR (202.5

MHz, CDCl₃) δ −26.7 (s); HRMS calcd for C₂₉H₂₅PFeSNa [M +

Na]⁺, 515.0657; found, 515.0654.

(R)-(3,5-Dimethylphenyl)phenyl[2-(phenylthiomethyl)phenyl]-

phosphine, 13e. The puriﬁcation was achieved by chromatography on

silica gel using a mixture of petroleum ether/dichloromethane (2:1) as

eluent. Colorless oil; yield 83% (0.103 g); R_f0.40 (petroleum ether/

dichloromethane, 2:1); 99% ee determined by HPLC analysis, after

complexation with borane, on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹,

3.76 (s, 3H), 3.99 (ABX syst, J = 1.3, 13.4 Hz, 1H), 4.08 (ABX syst, J =

1.3, 13.4 Hz, 1H), 6.72 (ddd, J = 1.7, 4.6, 6.4 Hz, 1H), 6.89−7.00 (m,

3H), 7.18 (td, J = 1.1, 7.4 Hz, 1H), 7.23−7.40 (m, 12H), 7.47−7.49

(m, 1H); ¹³C NMR (151 MHz, CDCl₃) δ 34.9 (d, J = 26.3 Hz), 36.5,

55.7, 110.3, 121.1, 125.3 (d, J = 8.4 Hz), 126.8, 127.1, 128.4 (2s),

128.6, 129.0, 129.5 (d, J = 4.4 Hz), 130.4, 133.9, 134.0, 134.1, 134.2,

135.8 (d, J = 10.1 Hz), 136.1 (d, J = 6.7 Hz), 138.4, 141.9 (d, J = 20.2

Hz), 161.2 (d, J = 17.0 Hz); ³¹P NMR (243 MHz, CDCl₃) δ −27.1

(s); HRMS calcd for C₂₇H₂₅PSONa [M + Na]⁺, 451.1256; found,

451.1258.

(S)-[2-(4-Methoxyphenylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine, 13j. The puriﬁcation was achieved by chromatog-

raphy on silica gel using a mixture of petroleum ether/dichloro-

methane (1:1) as eluent. Colorless oil; yield 83% (0.110 g); R_f0.49

(petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-1, 0.5 mL·min⁻¹, hexane/2-

propanol 98:2, t_R(S) = 14.2 min, t_R(R) = 15.9 min; [α]_D= −9.0 (c 0.3,

hexane/2-propanol, 98:2, t_R(R) = 8.6 min, t_R(S) = 9.8 min; [α]_D

=

+10.0 (c 0.3, CHCl₃); ¹H NMR (500 MHz, CD₂Cl₂) δ 2.31 (2s, 6H),

4.47 (brs, 2H), 6.96 (brs, 1H), 6.97 (brs, 1H), 7.02 (ddd, J = 1.4, 4.2,

7.7 Hz, 1H), 7.06 (brs, 1H), 7.21−7.41 (m, 12H), 7.50 (ddd, J = 0.9,

4.7, 7.7 Hz, 1H); ¹³C NMR (125.8 MHz, CD₂Cl₂) δ 21.0, 37.2 (d, J =

26.5 Hz), 126.1, 127.4, 128.4 (d, J = 7.1 Hz), 128.6, 128.7, 129.0,

129.4, 129.5, 130.6, 131.4, 131.6, 133.7, 133.9, 134.1, 136.1 (d, J = 9.5

Hz), 136.6 (d, J = 2.5 Hz), 136.7, 137.0 (d, J = 11.0 Hz), 138.1 (d, J =

7.5 Hz), 141.8 (d, J = 26.7 Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ

−16.9 (s); HRMS calcd for C₂₇H₂₅PSNa [M + Na]⁺, 435.1307; found,

435.1286.

1

CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ 3.77 (s, 3H), 3.80 (s, 3H),

4.36 (ABX syst, J = 1.6, 13.2 Hz, 1H), 4.42 (ABX syst, J = 1.6, 13.2 Hz,

1H), 6.69−6.72 (m, 1H), 6.81 (d, J = 8.5 Hz, 2H), 6.89−6.98 (m,

3H), 7.16 (t, J = 7.9 Hz, 1H), 7.25−7.30 (m, 5H), 7.36−7.41 (m, 5H);

¹³C NMR (125.8 MHz, CD₂Cl₂) δ 39.2 (d, J = 26.5 Hz), 55.2, 55.6,

(S)-[2-(Ethylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine, 13g. The puriﬁcation was accomplished by

chromatography on silica gel using a mixture of petroleum ether/

dichloromethane (1:1) as eluent and recrystallization in methanol/

dichloromethane. White solid; yield 90% (0.099 g); mp 88−90 °C; R_f

0.46 (petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-1, 0.5 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 10.7 min, t_R(R) = 11.9 min; [α]_D= −4.5 (c 0.3,

CHCl₃); ¹H NMR (600 MHz, CDCl₃) δ 1.20 (t, J = 7.6 Hz, 3H), 2.47

(qd, J = 4.0, 7.6 Hz, 2H), 3.77 (s, 3H), 4.03 (ABX syst, J = 2.3, 14.4

Hz, 1H), 4.11 (ABX syst, J = 2.3, 14.4 Hz, 1H), 6.70 (ddd, J = 1.6, 4.7,

7.3 Hz, 1H), 6.88−6.94 (m, 3H), 7.16 (td, J = 1.1, 7.6 Hz, 1H), 7.29−

7.39 (m, 7H), 7.56 (ddd, J = 0.9, 3.0, 7.9 Hz, 1H); ¹³C NMR (151

MHz, CDCl₃) δ 14.7, 25.7, 34.4 (d, J = 26.4 Hz), 55.7, 110.3, 121.1,

125.1 (d, J = 10.7 Hz), 127.0, 128.4 (d, J = 8.6 Hz), 128.6, 129.0, 129.5

(d, J = 4.4 Hz), 130.4, 133.8, 134.0, 134.1, 135.4 (d, J = 10.9 Hz, 136.1

(d, J = 8.2 Hz), 143.3 (d, J = 27.8 Hz), 161.0 (d, J = 16.7 Hz); ³¹P

NMR (243 MHz, CDCl₃) δ −27.1 (s); HRMS calcd for

C₂₂H₂₃PSONa [M + Na]⁺, 389.1089; found, 389.1099. X-ray quality

crystals were grown by slow evaporation of a CH₂Cl₂/methanol

solution.

110.4, 114.3, 121.0, 125.3 (d, J = 11.7 Hz), 126.5, 127.2, 128.3, 128.4,

128.5, 128.8, 129.6 (d, J = 4.7 Hz), 130.3, 133.4, 133.7 (d, J = 5.1 Hz),

133.9, 134.4, 136.0 (d, J = 13.8 Hz), 136.6 (d, J = 9.2 Hz), 159.1, 161.2

(d, J = 14.7 Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ −27.7 (s); HRMS

calcd for C₂₇H₂₅PSO₂Na [M + Na]⁺, 467.1205; found, 467.1215.

(S)-[2-(3, 5-Dimethylphenylthiomethyl)phenyl]-(2-

methoxyphenyl)phenylphosphine, 13l. The puriﬁcation was achieved

by chromatography on silica gel using a mixture of petroleum ether/

dichloromethane (1:1) as eluent. White gum; yield 86% (0.114 g); R_f

0.54 (petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 99:1, t_R(R) = 7.0 min, t_R(S) = 11.6 min; [α]_D= −5.5 (c 0.2,

1

CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ 2.28 (s, 6H), 3.77 (s, 3H),

4.44 (ABX syst, J = 1.6, 13.3 Hz, 1H), 4.49 (ABX syst, J = 2.0, 13.3 Hz,

1H), 6.72 (ddd, J = 1.8, 4.7. 7.6 Hz, 1H), 6.84 (brs, 1H), 6.90−6.99

(m, 5H), 7.19 (td, J = 1.3, 7.4 Hz, 1H), 7.30−7.42 (m, 7H), 7.49 (ddd,

J = 0.9, 4.8, 7.4 Hz, 1H); ¹³C NMR (125.8 MHz, CD₂Cl₂) δ 20.9, 37.0

(d, J = 27.3 Hz), 55.6, 110.4, 121.0, 125.3 (d, J = 12.7 Hz), 126.8,

127.3, 127.8, 128.4 (d, J = 7.2 Hz), 128.5, 128.9, 129.4 (d, J = 4.7 Hz),

130.3, 133.7 (d, J = 9.9 Hz), 133.9, 134.3, 136.1, 136.2 (d, J = 3.4 Hz),

136.5 (d, J = 10.4 Hz), 138.4, 142.1 (d, J = 26.2 Hz), 161.2 (d, J = 14.6

Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ −27.4 (s); HRMS calcd for

C₂₈H₂₇PSONa [M + Na]⁺, 465.1412; found, 465.1391.

(S)-[2-(tert-Butylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine, 13h. The puriﬁcation was achieved by chromatog-

raphy on silica gel using a mixture of petroleum ether/dichloro-

methane (1:1) as eluent and recrystallization in methanol/dichloro-

methane: white solid; yield 83% (0.098 g); mp 118−120 °C; R_f0.35

(petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 0.5 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 8.2 min, t_R(R) = 9.4 min; [α]_D= −20.9 (c 0.3,

(S)-[2-(4-Triﬂuoromethylphenyl)thiomethylphenyl]-(2-

methoxyphenyl)phenylphosphine, 13n. The puriﬁcation was

achieved by chromatography on silica gel using a mixture of petroleum

ether/dichloromethane (2:1) as eluent. Light yellow, sticky solid; yield

84% (0.121 g); R_f0.30 (petroleum ether/dichloromethane, 2:1);

enantiomeric excess 99% by HPLC analysis (Lux 5 μm cellulose-2, 1.0

mL·min⁻¹, hexane/2-propanol, 90:10, t_R(R) = 7.1 min, t_R(S) = 7.7

1

CHCl₃); H NMR (600 MHz, CDCl₃) δ 1.30 (s, 9H), 3.76 (s, 3H),

1

4.04 (ABX syst, J = 2.5, 12.9 Hz, 1H), 4.15 (ABX syst, J = 2.5, 12.9 Hz,

1H), 6.75 (ddd, J = 1.6, 5.0, 7.0 Hz, 1H), 6.89−6.94 (m, 3H), 7.14 (td,

J = 1.0, 7.5 Hz, 1H), 7.33−7.40 (m, 7H), 7.59 (ddd, J = 0.6, 4.7, 7.5

Hz, 1H); ¹³C NMR (151 MHz, CDCl₃) δ 30.9, 31.7 (d, J = 27.8 Hz),

43.1, 55.7, 110.4, 121.1, 125.7, 126.8, 128.4 (d, J = 7.4 Hz), 128.7,

129.1, 129.8 (d, J = 4.5 Hz), 130.5, 133.7, 134.0 (d, J = 7.7 Hz), 134.2,

134.8, 135.6, 143.2 (d, J = 23.9 Hz), 161.2 (d, J = 16.0 Hz); ³¹P NMR

(243 MHz, CDCl₃) δ −26.3 (s); HRMS calcd for C₂₄H₂₇PSONa [M +

Na]⁺, 417.1412; found, 416.1403. X-ray quality crystals were grown by

slow evaporation of a CH₂Cl₂/methanol solution.

min); [α]_D= −3.9 (c 0.3, CHCl₃); H NMR (600 MHz, CD₂Cl₂) δ

3.77 (s, 3H), 4.53 (ABX syst, J = 2.1, 13.6 Hz, 1H), 4.57 (ABX syst, J =

2.1, 13.6 Hz, 1H), 6.70−6.72 (m, 1H), 6.90−6.93 (m, 1H), 6.96−6.99

(m, 2H), 7.20−7.22 (m, 1H), 7.29−7.43 (m, 9H), 7.48−7.50 (m, 2H),

7.54−7.56 (m, 1H); ¹³C NMR (151 MHz, CD₂Cl₂) δ 35.9 (d, J = 28.6

Hz), 55.5, 110.5, 121.1, 124.8, 124.9, 125.4 (q, J = 3.4 Hz), 127.6 (d, J

= 14.1 Hz), 128.5 (d, J = 7.1 Hz), 128.7, 129.1, 129.2 (d, J = 4.4 Hz),

130.5, 133.7, 133.9, 134.0, 134.2, 136.0 (d, J = 9.9 Hz), 136.4 (d, J =

13.4 Hz), 140.8 (d, J = 10.7 Hz), 142.5, 161.2 (d, J = 15.4 Hz); ³¹P

NMR (243 MHz, CD₂Cl₂): δ −27.5 (s); HRMS calcd for

C₂₇H₂₂PSOF₃Na [M + Na]⁺, 505.0973; found, 505.0962.

(S)-[2-(Benzylthiomethyl)phenyl]-(2-methoxyphenyl)phenyl-

phosphine, 13i. The puriﬁcation was achieved by chromatography on

silica gel using a mixture of petroleum ether/dichloromethane (1:1) as

eluent. Colorless oil; yield 83% (0.107 g); R_f0.53 (petroleum ether/

dichloromethane, 1:1); 99% ee determined by HPLC analysis on Lux

5 μm cellulose-1, 0.5 mL·min⁻¹, hexane/2-propanol, 98:2, t_R(S) = 8.1

(S)-[2-(Tri-isopropylsilylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine, 13o. The puriﬁcation was achieved by chromatog-

raphy on silica gel using a mixture of petroleum ether/dichloro-

methane (1:1) as eluent. Colorless oil; yield 84% (0.125 g); R_f0.61

(petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(R) = 3.5 min, t_R(S) = 4.2 min; [α]_D= −3.9 (c 0.3,

1

min, t_R(R) = 9.1 min; [α]_D= +13.2 (c 0.3, CHCl₃); H NMR (600

MHz, CDCl₃) δ 3.67 (d, J = 13.4 Hz, 1H), 3.70 (d, J = 13.4 Hz, 1H),

N

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1

CHCl₃); H NMR (600 MHz, CD₂Cl₂) δ 1.11−1.12 (2d, J = 4.2 Hz,

10 mL). The combined organic phases were dried over MgSO₄, and

the solvent was removed under vacuum to give a residue, which was

diluted with toluene (3 mL). DABCO (0.07 g, 0.63 mmol) was added

under argon, and the resulting solution was stirred at room

temperature for 2 h. The solvent was then removed under vacuum,

and the residue was puriﬁed by chromatography on silica gel using a

mixture of petroleum ether/dichloromethane (1:1) as eluent. White

solid; overall yield (two steps) 58% (0.054 g); mp <40 °C; R_f0.33

(petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(R) = 10.9 min, t_R(S) = 13.6 min); [α]_D= +7.6 (c

18H), 1.24−1.29 (m, 3H), 3.78 (s, 3H), 3.98 (ABX syst, J = 2.5, 13.2

Hz, 1H), 4.07 (ABX syst, J = 2.5, 13.2 Hz, 1H), 6.71 (ddd, J = 1.8, 4.7,

7.5 Hz, 1H), 6.87−6.91 (m, 2H), 6.96 (dd, J = 4.9, 7.7 Hz, 1H), 7.16

(td, J = 0.9, 7.3 Hz, 1H), 7.29−7.32 (m, 2H), 7.36−7.41 (m, 3H), 7.66

(ddd, J = 0.7, 4.7, 7.5 Hz, 1H); ¹³C NMR (151 MHz, CD₂Cl₂) δ 12.7,

18.3, 28.6 (d, J = 28.3 Hz), 55.6, 110.4, 121.0, 125.1 (d, J = 11.8 Hz),

126.7, 128.4 (d, J = 6.8 Hz), 128.6, 128.9, 129.2 (d, J = 4.3 Hz), 130.3,

133.4, 133.9, 134.0, 134.2, 135.6 (d, J = 13.0 Hz), 136.4 (d, J = 11.2

Hz), 144.7 (d, J = 22.5 Hz), 161.3 (d, J = 16.8 Hz); ³¹P NMR (243

MHz, CD₂Cl₂) δ −26.7 (s); HRMS calcd for C₂₉H₃₉PSOSiNa [M +

Na]⁺, 517.2121; found, 517.2100.

1

0.3, CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ 3.78 (s, 3H), 3.89 (s,

3H), 4.44 (t, J = 2.5 Hz, 2H), 6.72 (ddd, J = 1.6, 4.6, 7.4 Hz, 1H),

6.84−6.99 (m, 5H), 7.12−7.22 (m, 3H), 7.29−7.33 (m, 3H), 7.37−

7.43 (m, 4H), 7.50 (ddd, J = 0.9, 4.8, 7.7 Hz, 1H); ¹³C NMR (125.8

MHz, CD₂Cl₂) δ 35.2 (d, J = 28.0 Hz), 55.7, 110.5, 120.9 (d, J = 29.5

Hz), 124.8, 125.2 (d, J = 13.0 Hz), 127.2 (d, J = 11.0 Hz), 128.4 (d, J =

7.0 Hz), 128.5, 128.9, 129.3 (d, J = 5.0 Hz), 129.7, 130.3, 133.7, 133.8,

134.0 (d, J = 14.2 Hz), 136.1 (d, J = 14.2 Hz), 136.5 (d, J = 10.7 Hz),

142.1 (d, J = 22.4 Hz), 157.3, 161.2 (d, J = 13.4 Hz); ³¹P NMR (202.5

MHz, CD₂Cl₂) δ −27.5 (s); HRMS calcd for C₂₇H₂₅PSO₂Na [M +

Na]⁺, 467.1205; found, 467.1199.

(S)-(2-Methoxyphenyl)phenyl[2-(phenylthioethyl)phenyl]-

phosphine, 13f. To a solution of phosphine-borane-sulﬁde 12f (0.14

g, 0.31 mmol) in toluene (2 mL) was added DABCO (0.10 g, 0.93

mmol). The reaction mixture was stirred for 2 h at room temperature,

and the solvent was removed under vacuum to give a residue, which

was puriﬁed by chromatography on silica gel using a mixture of

petroleum ether/dichloromethane (1:1) as eluent. Colorless oil; yield

88% (0.117 g); R_f0.48 (petroleum ether/dichloromethane, 1:1); 99%

ee determined by HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·

min⁻¹, hexane/2-propanol, 98:2, t_R(R) = 5.4 min, t_R(S) = 6.5 min;

1

[α]_D= +2.4 (c 0.2, CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ 3.12−

(S)-[2-(2,6-Dimethylphenylthiomethyl)phenyl]-(2-methoxy-

phenyl)phenylphosphine, 13m. To a solution of 2,6-dimethyl-

thiophenol (0.06 mL, 0.42 mmol) in dry THF (1 mL) was added at

0 °C n-BuLi (2.5 M in hexane) (0.20 mL, 0.50 mmol). The resulting

solution was stirred 20 min at 0 °C and 20 min at room temperature

and added to a solution of mesylate 11a (0.09 g, 0.21 mmol) in dry

THF (3 mL). After stirring for 20 min at room temperature, the

solution was quenched with water (5 mL) and extracted with

dichloromethane (3 × 10 mL). The combined organic phases were

dried over MgSO₄, and the solvent was removed under vacuum to give

a residue, which was diluted with toluene (3 mL). DABCO (0.07 g,

0.63 mmol) was added under argon, and the resulting solution was

stirred at room temperature for 2 h. The solvent was then removed

under vacuum, and the residue was puriﬁed by chromatography on

silica gel using a mixture of petroleum ether/dichloromethane (1:1) as

eluent. White sticky solid; overall yield (two steps) 58% (0.054 g); R_f

0.50 (petroleum ether/dichloromethane, 1:1); 99% ee determined by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 3.9 min, t_R(R) = 4.6 min; [α]_D= −32.4 (c 0.2,

3.30 (m, 4H), 3.77 (s, 3H), 6.71 (ddd, J = 1.7, 4.5, 7.5 Hz, 1H), 6.90−

6.99 (m, 3H), 7.16−7.23 (m, 2H), 7.28−7.42 (m, 12H); ¹³C NMR

(125.8 MHz, CD₂Cl₂) δ 34.3 (d, J = 4.4 Hz), 34.8 (d, J = 20.7 Hz),

55.7, 110.5 (d, J = 1.1 Hz), 121.1, 125.4 (d, J = 11.7 Hz), 125.6, 126.8,

128.4 (d, J = 8.3 Hz), 128.6 (d, J = 6.7 Hz), 128.8, 129.0, 129.7 (d, J =

5.0 Hz), 130.4, 133.6, 133.9, 134.1 (2s), 135.5 (d, J = 12.4 Hz), 136.4

(d, J = 10.8 Hz), 136.6, 145.0 (d, J = 25.7 Hz), 161.1 (d, J = 12.9 Hz);

³¹P NMR (202.5 MHz, CD₂Cl₂) δ −26.8 (s); HRMS calcd for

C₂₇H₂₅PSONa [M + Na]⁺, 451.1256; found, 451.1247.

Method B: Preparation of Phosphine-Sulﬁdes 13 from

Mesylates 11. (S)-(o-Biphenyl)-[2-(phenylthiomethyl)phenyl]-

phenylphosphine, 13c. To a solution of thiophenol (0.06 mL, 0.56

mmol) in dry THF (1 mL) was added 0.28 mL of n-BuLi (0.68 mmol,

2.5 M in hexane) at 0 °C. The resulting solution was stirred 20 min at

0 °C and 20 min at room temperature and added to a solution of

mesylate 11c (0.13 g, 0.28 mmol) in dry THF (3 mL). After stirring

for 20 min at room temperature, the solution was quenched with water

(5 mL) and extracted with dichloromethane (3 × 10 mL). The

combined organic phases were dried over MgSO₄, and the solvent was

removed under vacuum to give a residue, which was diluted with

toluene (3 mL). DABCO (0.10 g, 0.84 mmol) was added under argon,

and the resulting solution was stirred at room temperature for 2 h. The

solvent was then removed under vacuum, and the residue was puriﬁed

by chromatography column on silica gel using a mixture of petroleum

ether/dichloromethane (2:1) as eluent. White solid; overall yield (two

steps) 74% (0.095 g); mp 114−116 °C; R_f0.41 (petroleum ether/

dichloromethane, 2:1); 99% ee determined by HPLC analysis on Lux

5 μm cellulose-1, 0.5 mL·min⁻¹, hexane/2-propanol, 98:2, t_R(S) = 11.2

1

CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ 2.45 (s, 6H), 3.79 (s, 3H),

4.13 (ABX syst, J = 1.3, 12.5 Hz, 1H), 4.20 (ABX syst, J = 1.3, 12.5 Hz,

1H), 6.73 (ddd, J = 1.7, 4.5, 7.5 Hz, 1H), 6.90−6.99 (m, 3H), 7.07−

7.19 (m, 5H), 7.25 (td, J = 1.4, 7.4 Hz, 1H), 7.30−7.43 (m, 6H); ¹³C

NMR (125.8 MHz, CD₂Cl₂) δ 21.7, 38.4 (d, J = 26.1 Hz), 55.6, 110.4,

121.0, 125.4 (d, J = 12.7 Hz), 127.2, 127.9, 128.3, 128.4, 128.5, 128.7,

129.8 (d, J = 4.2 Hz), 130.3, 133.4, 133.8 (d, J = 9.0 Hz), 134.0, 134.3,

135.9 (d, J = 14.4 Hz), 136.6 (d, J = 10.8 Hz), 143.0 (d, J = 24.7 Hz),

143.7, 161.2 (d, J = 12.4 Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ

−27.4 (s); HRMS calcd for C₂₈H₂₈PSO [M + H]⁺, 443.1593; found,

443.1607.

1

min, t_R(R) = 12.5 min; [α]_D= +11.5 (c 0.3, CHCl₃); H NMR (500

MHz, CD₂Cl₂) δ 4.12 (AB syst, J = 13.5 Hz, 1H), 4.24 (ABX syst, J =

2.2, 13.5 Hz, 1H), 7.06 (ddd, J = 1.3, 3.8, 7.6 Hz, 1H), 7.12−7.40 (m,

21H), 7.47 (td, J = 1.3, 7.5 Hz, 1H); ¹³C NMR (125.8 MHz, CD₂Cl₂)

δ 37.2 (d, J = 26.0 Hz), 125.9, 127.1, 127.4 (d, J = 6.4 Hz), 127.6,

128.4, 128.5 (d, J = 2.1 Hz), 128.7, 128.8, 128.9, 129.1, 129.4 (d, J =

4.3 Hz), 129.6 (d, J = 4.3 Hz), 130.2 (d, J = 4.3 Hz), 133.9, 134.0,

134.1, 134.7, 135.5 (d, J = 13.8 Hz), 136.7, 136.9, 137.0 (d, J = 3.1

Hz), 141.6 (d, J = 26.0 Hz), 141.9 (d, J = 6.4 Hz), 148.1 (d, J = 29.1

Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ −24.4 (s); HRMS calcd for

C₃₁H₂₅PSNa [M + Na]⁺, 483.1307; found, 483.1290.

(S)-[2-(2-Methoxyphenylthiomethyl)phenyl]-(2-methoxyphenyl)-

phenylphosphine, 13k. To a solution of 2-methoxythiophenol (0.05

mL, 0.42 mmol) in dry THF (1 mL) was added at 0 °C n-BuLi (2.5 M

in hexane) (0.20 mL, 0.50 mmol). The resulting solution was stirred

20 min at 0 °C and 20 min at room temperature and added to a

solution of mesylate 11a (0.09 g, 0.21 mmol) in dry THF (3 mL).

After stirring for 20 min at room temperature, the solution was

quenched with water (5 mL) and extracted with dichloromethane (3 ×

(S)-(o-Biphenyl)-[2-(2,6-dimethylphenylthiomethyl)phenyl]-

phenylphosphine, 13p. To a solution of 2,6-dimethylthiophenol (0.06

mL, 0.42 mmol) in dry THF (1 mL) was added 0.20 mL of n-BuLi

(2.5 M in hexane; 0.50 mmol) at 0 °C. The resulting solution was

stirred 20 min at 0 °C and 20 min at room temperature and added to a

solution of mesylate 5c (0.10 g, 0.21 mmol) in dry THF (3 mL). After

stirring for 20 min at room temperature, the solution was quenched

with water (5 mL) and extracted with dichloromethane (3 × 10 mL).

The combined organic phases were dried over MgSO₄, and the solvent

removed under vacuum to give a residue, which was diluted with

toluene (3 mL). DABCO (0.07 g, 0.63 mmol) was added under argon,

and the resulting solution was stirred at room temperature for 2 h. The

solvent was then removed under vacuum, and the residue was puriﬁed

by chromatography on silica gel using a mixture of petroleum ether/

dichloromethane (1:1) as eluent. White sticky solid; overall yield (two

steps) 63% (0.065 g); R_f0.42 (petroleum ether/dichloromethane,

1

2:1); [α]_D= +5.5 (c 0.2, CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ

2.34 (s, 6H), 3.76 (AB syst, J = 12.7 Hz, 1H), 4.01 (ABX syst, J = 2.3,

O

DOI: 10.1021/acs.organomet.5b00585

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12.7 Hz, 1H), 7.03 (ddd, J = 1.4, 3.7, 7.6 Hz, 1H), 7.07−7.13 (m, 5H),

7.18−7.38 (m, 14H), 7.45 (td, J = 1.4, 7.6 Hz, 1H); ¹³C NMR (125.8

MHz, CD₂Cl₂) δ 21.7 (2s), 38.4 (d, J = 25.8 Hz), 127.0, 127.2, 127.4,

127.6, 127.8, 128.3 (2s), 128.4 (2s), 128.7 (d, J = 4.2 Hz), 129.6 (2s),

129.8 (d, J = 5.0 Hz), 130.2 (d, J = 4.2 Hz), 133.4, 133.9, 134.1, 134.2,

134.6, 135.7 (d, J = 14.7 Hz), 136.5 (d, J = 14.7 Hz), 137.2 (d, J = 10.7

Hz), 141.8 (d, J = 7.8 Hz), 143.0 (d, J = 26.1 Hz), 143.6, 148.1 (d, J =

28.7 Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ −24.2 (s); HRMS calcd

for C₃₃H₃₀PS [M + H]⁺, 489.1800; found, 489.1788.

(m, 1H), 4.02−4.07 (m, 1H), 4.07 (s, 3H), 6.65 (dd, J = 6.8, 11.3 Hz,

1H), 6.76 (t, J = 5.6 Hz, 1H), 7.02 (td, J = 1.1, 7.5 Hz, 1H), 7.13−7.42

(m, 8H), 7.58−7.71 (m, 7H); ¹³C NMR (125.8 MHz, CD₂Cl₂) δ 40.5

(d, J = 12.9 Hz), 56.6, 112.1 (d, J = 4.5 Hz), 116.3 (d, J = 66.9 Hz),

120.9 (d, J = 11.2 Hz), 122.7 (d, J = 53.5 Hz), 124.6 (d, J = 53.5 Hz),

127.9, 129.2, 129.5 (d, J = 12.1 Hz), 130.8, 131.7, 132.2 (d, J = 8.6

Hz), 132.7 (d, J = 3.4 Hz), 133.5 (d, J = 5.2 Hz), 133.6, 134.0 (d, J =

3.4 Hz), 134.2, 137.6 (d, J = 13.3 Hz), 160.7; ³¹P NMR (202.5 MHz,

CD₂Cl₂) δ + 18.8 (s); HRMS calcd for C₂₆H₂₃PSOClPd [M − Cl]⁺,

554.9932; found, 554.9950. X-ray quality crystals were grown by slow

evaporation of a CH₂Cl₂/diethyl ether solution.

Synthesis of (R)-(2-Methoxyphenyl)phenyl[2-(phenylthio)-

phenyl]phosphine, 13q. To a solution of (2-bromophenyl)-

phenylsulﬁde (16a) (0.13 g, 0.50 mmol) in THF (2 mL) was added

at −78 °C under argon 0.22 mL of n-BuLi (2.5 M in hexane; 0.55

mmol), and the resulting solution was stirred at this temperature for 1

h. At this time, a solution of o-anisyl-phenyl-phenylphosphinite (15),

previously prepared according to a literature procedure^16b,18,21(0.29 g,

0.60 mmol), in THF (5 mL) was added dropwise at −78 °C, and the

mixture was stirred at room temperature overnight. After quenching

the reaction with water, the mixture was extracted with methylene

chloride (3 × 5 mL) and the organic phases were dried over MgSO₄.

The solvent was evaporated under vacuum to give a residue, which was

puriﬁed by chromatography on silica gel using a mixture of petroleum

ether/ethyl acetate (5:1) as eluent. White sticky solid; yield 39%

(0.078 g); R_f0.31 (petroleum ether/ethyl acetate, 5:1); 99% ee

determined by HPLC analysis on Lux 5 μm cellulose-1, 0.5 mL·min⁻¹,

hexane/2-propanol, 98:2, t_R(S) = 13.6 min, t_R(R) = 14.3 min; [α]_D=

Complex 27. A solution of phosphine-sulﬁde 13f (0.032 g, 0.075

mmol) and Pd(CH₃CN)₂Cl₂(0.019 g, 0.072 mmol) in dry CH₂Cl₂

(1.5 mL) was stirred 2 h under argon at room temperature. Diethyl

ether (10 mL) was then added, and the resulting precipitate was

ﬁltered and washed with diethyl ether (3 × 5 mL) to aﬀord the

palladium complex 27 as a pale yellow powder. Yield: 65% (0.029 g);

1

mp 192−194 °C (dec); H NMR (500 MHz, CD₂Cl₂) δ 3.05−3.14

(m, 2H), 3.30−3.36 (m, 1H), 3.72, d, J = 10.5 Hz, 1H), 3.97 (s, 3H),

7.03−7.19 (m, 4H), 7.25 (ddd, J = 1.1, 4.8, 7.5 Hz, 1H), 7.36 (tt, J =

1.5, 7.8 Hz, 1H), 7.40−7.56 (m, 8H), 7.56−7.61 (m, 1H), 7.65−7.69

(m, 1H), 8.00 (brs, 2H); ¹³C NMR (125.8 MHz, CD₂Cl₂) δ 32.6 (d, J

= 9.9 Hz), 38.7, 56.2, 111.8 (d, J = 5.9 Hz), 116.8 (d, J = 63.4 Hz),

120.9 (d, J = 11.9 Hz), 126.8, 127.2, 127.4 (d, J = 52.5 Hz), 128.2 (d, J

= 8.3 Hz), 128.5, 128.6, 128.7, 129.8, 130.4 (d, J = 8.3 Hz), 130.9,

131.7 (d, J = 2.8 Hz), 132.4 (d, J = 2.8 Hz), 132.6 (brs), 133.8 (d, J =

1.8 Hz), 134.7 (brs), 140.6 (d, J = 15.6 Hz), 160.2 (d, J = 4.6 Hz); ³¹P

NMR (202.5 MHz, CD₂Cl₂) δ + 16.2 (s); HRMS calcd for

C₂₇H₂₅PSOPdCl [M − Cl]⁺, 569.0088; found, 569.0092.

1

−34.7 (c 0.3, CHCl₃); H NMR (500 MHz, acetone-D₆) δ 3.75 (s,

3H), 6.65 (ddd, J = 1.7, 4.3, 7.5 Hz, 1H), 6.88−6.93 (m, 2H), 7.06

(dd, J = 4.2, 7.6 Hz, 1H), 7.25−7.30 (m, 6H), 7.31−7.35 (m, 4H),

7.39−7.41 (m, 4H); ¹³C NMR (125.8 MHz, acetone-D₆) δ 55.1,

110.7, 121.0, 125.5 (d, J = 15.6 Hz), 126.8, 127.7, 128.5 (d, J = 7.3

Hz), 128.7, 129.1, 129.6, 130.5, 132.9 (d, J = 2.6 Hz), 133.4 (d, J = 1.8

Hz), 133.5, 134.0, 134.2, 136.6−136.7 (m), 140.6, 140.7 (d, J = 43.3

Hz), 161.3 (d, J = 14.4 Hz); ³¹P NMR (202.5 MHz, acetone-D₆) δ

−21.6 (s); HRMS calcd for C₂₅H₂₁PSONa [M + Na]⁺, 423.0943;

found, 423.0929.

Complex 26. A solution of phosphine-sulﬁde 13q (0.054 g, 0.125

mmol) and Pd(CH₃CN)₂Cl₂(0.029 g, 0.113 mmol) in dry CH₂Cl₂

(2.5 mL) was stirred under argon at room temperature for 2 h. Diethyl

ether (20 mL) was then added, and the resulting precipitate was

ﬁltered and washed with diethyl ether (3 × 10 mL) to aﬀord the

palladium complex 26 as a pale yellow powder. Yield: 65% (0.042 g);

mp 210−212 °C (dec); ¹H NMR (500 MHz, CD₂Cl₂) δ 3.77 (s, 3H),

7.06−7.11 (m, 2H), 7.35−7.72 (m, 14H), 7.95 (brs, 2H); ¹³C NMR

(125.8 MHz, CD₂Cl₂) δ 56.3, 112.5 (d, J = 6.0 Hz), 115.5 (d, J = 60.0

Hz), 121.0 (d, J = 10.0 Hz), 129.1 (d, J = 11.5 Hz), 129.6, 130.6, 131.1

(d, J = 5.7 Hz), 132.2, 132.6 (d, J = 15.1 Hz), 133.7 (brs), 134.0, 134.2

(brs), 135.0 (2s), 137.9 (d, J = 55.0 Hz), 160.6 (d, J = 4.1 Hz); ³¹P

NMR (202.5 MHz, CD₂Cl₂) δ + 50.4 (s); HRMS calcd for

C₂₅H₂₂PSOPd [M − 2Cl + H]⁺, 507.0167; found, 507.0148. X-ray

quality crystals were grown by slow evaporation of a CH₂Cl₂/diethyl

ether solution.

Complex 28. A solution of phosphine-sulﬁde 13r (0.048 g, 0.125

mmol) and Pd(CH₃CN)₂Cl₂(0.029 g, 0.113 mmol) in dry CH₂Cl₂

(2.5 mL) was stirred 2 h under argon at room temperature. Diethyl

ether (20 mL) was then added, and the resulting precipitate was

ﬁltered and washed with diethyl ether (3 x10 mL) to aﬀord the

palladium complex as a pale yellow powder. Yield: 63% (0.040 g); mp

204−206 °C (dec); ¹H NMR (600 MHz, CD₂Cl₂) δ 1.40 (s, 9H), 3.68

(s, 3H), 6.93−6.99 (m, 3H), 7.46−7.47 (m, 1H), 7.60−7.72 (m, 6H),

7.85−8.86 (m, 1H), 8.20 (brs, 2H); ¹³C NMR (125.8 MHz, CD₂Cl₂)

δ 30.8, 56.4, 60.4, 112.6, 118.2 (d, J = 68.4 Hz), 120.6 (d, J = 10.5 Hz),

125.6 (d, J = 57.9 Hz), 129.2, 129.3, 131.0 (d, J = 5.3 Hz), 132.2,

132.6, 134.0, 134.4, 134.5, 134.6, 137.0 (d, J = 21.0 Hz), 139.8 (d, J =

57.9 Hz), 160.0; ³¹P NMR (202.5 MHz, CD₂Cl₂) δ + 47.2 (s); HRMS

calcd for C₁₉H₁₆PSOPd [M-2Cl-(t-Bu)]⁺, 428.9696; found, 428.9689.

General Procedure for Allylic Alkylation of Dimethyl

Malonate. To a Schlenk tube containing phosphine-sulﬁde 13

(0.02 mmol), [Pd(C₃H₅)Cl₂] (0.01 mmol), and substrate 17, 18, or

19 (0.5 mmol) was added toluene or CH₂Cl₂(4 mL). The mixture

was stirred 30 min at room temperature. Dimethylmalonate (0.12 mL,

1.0 mmol) followed by N,O-bis(trimethylsilyl)acetamide (0.24 mL, 1.0

mmol) and a pinch of potassium acetate were added. After 1 h, the

reaction was diluted with diethyl ether and washed with saturated

NH₄Cl solution. The organic phase was dried over MgSO₄, ﬁltered,

and concentrated in vacuo to give a residue, which was puriﬁed by

Synthesis of (R)-(2-Methoxyphenyl)phenyl[2-(tert-butylthio)-

phenyl]phosphine, 13r. To a solution of (2-bromophenyl)-tert-

butylsulﬁde (16b) (0.32 g, 1.30 mmol) in THF (2 mL) was added

at −78 °C under argon n-BuLi (2.5 M in hexane) (0.0.57 mL, 1.43

mmol), and the resulting solution was stirred at this temperature for 1

h. At this time, a solution of o-anisyl-phenyl-phenylphosphinite 15,

previously prepared according to a literature procedure^16b,18,21(0.44 g,

1.43 mmol), in THF (3 mL) was added dropwise at −78 °C, and the

mixture was stirred at room temperature overnight. After quenching

the reaction with water, the mixture was extracted with methylene

chloride (3 × 5 mL), and the organic phases were dried over MgSO₄.

The solvent was evaporated under vacuum to give a residue, which was

puriﬁed by chromatography on silica gel using a mixture of petroleum

ether/dichloromethane (1:1) as eluent. White sticky solid; yield 56%

(0.27 g); R_f0.48 (petroleum ether/dichloromethane, 1:1); 99% ee by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 98:2, t_R(S) = 4.0 min, t_R(R) = 4.8 min; [α]_D= −50.9 (c 0.2,

1

CHCl₃); H NMR (500 MHz, CD₂Cl₂) δ 1.42 (s, 9H), 3.74 (s, 3H),

6.56 (ddd, J = 1.7, 3.8, 7.5 Hz, 1H), 6.85−6.88 (m, 2H), 6.96 (ddd, J =

0.8, 4.8, 8.3 Hz, 1H), 7.22−7.27 (m, 3H), 7.34−7.37 (m, 5H), 7.65

(ddd, J = 1.1, 4.4, 7.7 Hz, 1H); ¹³C NMR (125.8 MHz, CD₂Cl₂) δ 30.9

(d, J = 2.7 Hz), 48.1, 55.6, 110.4, 121.0, 127.1 (d, J = 17.0 Hz), 128.3

(d, J = 6.7 Hz), 128.4, 128.6 129.9, 133.5, 133.7, 134.0, 134.2, 137.6

(d, J = 14.2 Hz), 137.8, 138.4, 145.1 (d, J = 9.8 Hz), 161.0 (d, J = 14.6

Hz); ³¹P NMR (202.5 MHz, CD₂Cl₂) δ −21.4 (s); HRMS calcd for

C₂₃H₂₆PSO [M + H]⁺, 381.1437; found, 381.1449.

Preparation of Dichloropalladium Complex Pd(13)Cl₂.

Complex 25. A solution of phosphine-sulﬁde 13a (0.031 g, 0.074

mmol) and Pd(CH₃CN)₂Cl₂(0.018 g, 0.071 mmol) in dry CH₂Cl₂

(1.5 mL) was stirred 2 h under argon at room temperature. Diethyl

ether (10 mL) was then added, and the resulting precipitate was

ﬁltered and washed with diethyl ether (3 × 5 mL) to aﬀord the

palladium complex 25 as a pale yellow powder. Yield: 67% (0.028 g);

1

mp 206−208 °C (dec); H NMR (500 MHz, CD₂Cl₂) δ 3.43−3.46

P

DOI: 10.1021/acs.organomet.5b00585

Organometallics XXXX, XXX, XXX−XXX

Organometallics

Article

chromatography on silica gel using a mixture of petroleum ether/ethyl

acetate (5:1) as eluent.

complexes 25−28; computational calculations and

stereoscopic view of palladium complexes 29, 25, 26,

and 30 (PDF)

(E)-Methyl-2-methoxycarbonyl-3,5-diphenylpent-4-enoate, 20:

¹H NMR (300 MHz, CDCl₃) δ 3.56 (s, 3H), 3.75 (s, 3H), 4.02 (d,

J = 10.9 Hz, 1H), 4.27 (dd, J = 8.8, 10.8 Hz, 1H), 6.40 (dd, J = 8.6,

15.7 Hz, 1H), 6.54 (d, J = 15.7 Hz, 1H), 7.10−7.40 (m, 10H). The

enantiomeric excess was determined by HPLC analysis on Chiralpak

IA, 1.0 mL·min⁻¹, hexane/2-propanol, 90:10, λ = 254 nm, t_R(R) = 8.6

min, t_R(S) = 10.4 min.

AUTHOR INFORMATION

Corresponding Authors

*E-mail: Jerome.bayardon@u-bourgogne.fr. Tel: +33 (0)3 80

39 61 02.

■

(E)-Methyl-2-methoxycarbonyl-3-methylhex-4-enoate, 21: ¹H

NMR (300 MHz, CDCl₃) δ 0.90 (d, J = 6.7 Hz, 3H), 1.47 (dd, J =

1.0, 6.3 Hz, 3H), 2.70−2.78 (m, 1H), 3.11 (d, J = 9.1 Hz, 1H), 3.53 (s,

3H), 3.57 (s, 3H), 5.14−5.23 (m, 1H), 5.33−5.40 (m, 1H). The

enantiomeric excess was determined by HPLC analysis on Chiralpak

IA, 1.0 mL·min⁻¹, hexane/2-propanol, 99:1, λ = 210 nm, t_R(S) = 9.1

min, t_R(R) = 12.5 min.

*E-mail: Sylvain.Juge@u-bourgogne.fr. Tel: +33 (0)3 80 39 61

13.

Notes

The authors declare no competing ﬁnancial interest.

Dimethyl-3-cyclohexenylmalonate, 22: ¹H NMR (300 MHz,

CDCl₃) δ 1.38−1.46 (m, 1H), 1.57−1.83 (m, 3H), 2.00−2.07 (m,

2H), 3.33 (d, J = 9.7 Hz, 1H), 3.78 (2s, 6H), 5.53−5.59 (m, 1H),

5.79−5.84 (m, 1H). The enantiomeric excess was determined by

HPLC analysis on Lux 5 μm cellulose-2, 1.0 mL·min⁻¹, hexane/2-

propanol, 99:1, λ = 210 nm, t_R(S) = 20.1 min, t_R(R) = 21.6 min.

General Procedure for Allylic Alkylation of Benzylamine. To

a Schlenk tube containing phosphine-sulﬁde 13 (0.02 mmol),

[Pd(C₃H₅)Cl₂] (0.01 mmol), and substrate 17 (0.5 mmol) was

added dichloromethane (4 mL). The mixture was stirred 30 min at

room temperature, and dimethylmalonate (0.12 mL, 1.0 mmol)

followed by TBAF (1 M in THF) (1.0 mL, 1.0 mmol) were added.

After 3−4 h, the reaction was diluted with diethyl ether and washed

with a saturated NH₄Cl solution. The organic phase was dried over

MgSO₄, ﬁltered, and concentrated in vacuo to give a residue, which was

puriﬁed by chromatography on silica gel using a mixture of petroleum

ether/ethyl acetate (5:1) as eluent.

ACKNOWLEDGMENTS

■

The authors are grateful for the ﬁnancial support provided by

the “Minister

̀

e de l’Education Nationale et de la Recherche”,

the CNRS (Centre National de la Recherche Scientiﬁque), the

“Conseil Regional de Bourgogne” (grants 3MIM and CDEA/

SMT8). The authors would like also to thank M. J. Penouilh,

̂ ́

M. and F. Picquet at the Welience/Pole Chimie Moleculaire for

the NMR and mass spectrometry analyses and M. J. Eymin for

her skilled technical assistance. A.L. thanks NSERC (Natural

Sciences and Engineering Research Council of Canada) for a

postgraduate scolarship.

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R

DOI: 10.1021/acs.organomet.5b00585

Organometallics XXXX, XXX, XXX−XXX

Organometallics

Article

NOTE ADDED AFTER ASAP PUBLICATION

■

Due to a production error, this paper was published on the

Web on August 27, 2015, with errors in the Results and

Discussion section, the Experimental Section, and the

Supporting Information. The corrected version was reposted

on August 28, 2015.

S

DOI: 10.1021/acs.organomet.5b00585

Organometallics XXXX, XXX, XXX−XXX

Article Doi

Modular P-Chirogenic Phosphine-Sulfide Ligands: Clear Evidence for Both Electronic Effect and P-Chirality Driving Enantioselectivity in Palladium-Catalyzed Allylations

DOI: 10.1021/acs.organomet.5b00585

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