An asymmetric biaryl Suzuki cross-coupling reaction: Stereogenic benzylic carbinols as chiral auxiliaries

FULL PAPER

An Asymmetric Biaryl Suzuki Cross-Coupling Reaction: Stereogenic Benzylic

Carbinols as Chiral Auxiliaries

Pierre-Emmanuel Broutin^[a]and Françoise Colobert*^[a]

Keywords: Asymmetric synthesis / Cross-coupling / Palladium / Suzuki reaction / Stereogenic carbinol / Sulfoxides

Asymmetric biaryl Suzuki coupling reactions were per-

formed with various aryl- or naphthylhalide-bearing enantio-

merically pure benzylic alcohols and aryl- or naphthylbo-

ronic acids (or esters). The stereogenic benzylic alcohol was

introduced by diastereoselective reduction of the arylhalide

bearing a β-keto sulfoxide. In the presence of Pd(OAc)₂/CsF

and dppf or PPh₃excellent yields and atropodiastereoselec-

tivities were obtained. The absolute configurations of the bi-

aryls were determined by X-ray crystallography and ¹H

NMR NOESY experiments.

Germany, 2005)

yls by Suzuki coupling. The first one, described by Uemu-

ra,^[5i]consists of using chiral arene(chromium)halide com-

Introduction

ortho-Substituted biphenyls (or more generally biaryls)^[1–4]plexes. The second is another atropodiastereoselective

are found in a wide variety of natural products including method reported by Lipshutz using a stereocenter attached

alkaloids, coumarins, flavonoids, lignans, etc. Compounds to a phosphane ligand as chiral auxiliary.^[5e]In the third

incorporating biaryl building blocks also find applications strategy, the atroposelectivity is induced by chiral catalysts.

as chiral reagents, chiral phases for chromatography, and This was first illustrated in the total synthesis of Vancomy-

chiral liquid crystals. Many efficient methodologies for cin^[7]by Nicolaou, who obtained a chiral biaryl with up to

asymmetric coupling between the two aromatic portions 55% diastereomeric excess in the presence of a chiral ligand.

have been described using either chiral ligands, stoichiomet- Enantioselective Suzuki couplings induced by a chiral li-

ric chiral auxiliaries, or chiral starting materials.^[5]Cur- gand have also been reported by Cammidge,^[8]Buchwald,^[9]

rently, a very important challenge in the synthetic useful- Baudoin,^[10]Johannsen,^[11]and, very recently, by Mi-

ness of this biaryl coupling reaction is the development of kami.^[12]We recently communicated the use of BINAP or

a highly efficient asymmetric version.

Tol-BINAP in the synthesis of 2,2Ј-dimethoxy-1,1Ј-dinaph-

Since its discovery in 1981 the Suzuki–Miyaura coup- thalene, and showed that the ligand-to-palladium ratio in-

ling^[6]has become a powerful tool for the construction of a fluences the sense of the enantioselection.^[13]

biaryl bond due to its efficiency and wide functional-group

We report here the use of benzylic carbinols as efficient

tolerance. However, efficient methodologies for an asym- stereochemical controllers in the biaryl Suzuki coupling re-

metric Suzuki biaryl coupling reaction are relatively rare action.^[14]This stereogenic alcohol was introduced by the

and have been reported only in the past few years. Three reduction of a β-keto sulfoxide^[15]in the position ortho to

strategies have been applied for the synthesis of chiral biar- the aryl halide unit (Scheme 1).

Scheme 1. Palladium-catalyzed Suzuki coupling with an aryl iodide bearing a β-hydroxysulfoxide

The presence of a chiral center such as a chiral benzylic

alcohol in the ortho position of the aryl halide could be

[a] Laboratoire de stéréochimie associé au CNRS, Université Louis

Pasteur (ECPM)

very useful in the total synthesis of biologically active com-

25 Rue Becquerel, 67087 Strasbourg, France

Fax: +33-3-90-24-27-42

pounds such as (–)-Steganacin,^[16]Korupensamine A,^[17]

and the biaryl unit of Vancomycine,^[18]which could arise

from precursors bearing a benzylic stereocenter (Scheme 2).

E-mail: fcolober@chimie.u-strasbg.fr

Supporting information for this article is available on the

WWW under http://ww w .eurjoc.org or from the author.

Eur. J. Org. Chem. 2005, 1113–1128

DOI: 10.1002/ejoc.200400638

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P.-E. Broutin, F. Colobert

FULL PAPER

Scheme 2. Retrosynthesis of Steganacin, Korupensamine A, and Vancomycin

Table 1. Suzuki reactions of 1–3 with 2-methoxy-1-naphthylboronic acid (4)

Entry^[a]

Substrate

Solvent

Ligand

Biaryl, yield (%)^[b]

dr^[c]

1

2

3

4

5

6

7

8

9

1

2

3

DME

PPh₃

dppf

BINAP

(R)-BINAP

dppf

5, 28

5, 38

5, 69

5, 58

5, 54

5, 56

5, 57

5, 60

6, 33

7, 15

60:40

65:35

60:40

70:30

60:40

70:30

60:40

DME

dioxane

THF

dioxane

DME

A

B

dppf

10

dppf

[a] Reaction conditions: 1–3 (1 equiv.), 4 (1.5 equiv.), Pd(OAc)₂(10 mol%), ligand (15 or 30 mol%), CsF (4.5 equiv.), 50 °C, 3–5 h. [b]

1

Yield of product isolated after chromatography. [c] Determined by H NMR spectroscopy after chromatography.

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Eur. J. Org. Chem. 2005, 1113–1128

Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

Simultaneously to our first communication,^[14]a dia- phenyl^[25](Ligand A)] or imidazolidine ligand [1,3-bis(2,6-

stereoselective Suzuki coupling between a chiral benzylic diisopropylphenyl)imidazolidine^[26](Ligand B)] (Table 1).

alcohol and sterically hindered arylboronic esters was re-

ported in an approach to cyclooctadiene lignans.^[19]

In the coupling reaction with the iodophenyl-containing

β-keto-p-tolylsulfoxide 1, dppf was found to give the best

diastereomeric ratio^[27]in dioxane or THF with CsF as base

(Table 1, entries 5 and 8) but no reaction occurred in the

presence of Ag₂CO₃or K₃PO₄. Changing the substitution

at the sulfoxide did not improve the selectivity and de-

creased the yield (Table 1, entries 9 and 10).

Results and Discussion

Search for the Optimal Experimental Conditions for the

Suzuki Coupling Reaction with Aryl-Halides-Containing β-

Keto Sulfoxides

Suzuki Coupling Reactions with Aryl-Halide-Containing β-

Hydroxysulfoxides

Recently we reported an efficient Suzuki cross-coup-

ling^[13]of sterically hindered substrates inDME using ce-

sium fluoride as a base and Pd(OAc)₂/PPh₃as catalyst. In

order to study the induction from the stereogenic β-keto

sulfoxide to the chiral axis we first explored the Suzuki

coupling reaction between 2-methoxy-1-naphthylboronic

acid (4)^[20]and the readily available enantiopure 1-[(+)-aryl

or (–)-tert-butylsulfinyl]-2-(o-iodophenyl)-2-ethanone (1–3)

under previously reported conditions^[13](Table 1). The

preparation of compounds 1–3 was achieved in good yields

by condensation of the lithiated anion of (+)-[(S)R] methyl

p-tolyl sulfoxide,^[21](+)-[(S)R] (o-dimethylaminophenyl)

methyl sulfoxide,^[22]or (–)-[(S)S] tert-butyl methyl sulfox-

ide^[23]to 2-iodo-1-methylbenzoate in THF (Scheme 3).

In view ofthe modest induction with the β-keto sulfoxide

auxiliaries we reduced the β-keto sulfoxide 1 in order to

obtain the desired stereogenic benzylic alcohol. The re-

duction was performed with DIBAL in the presence of

ZnBr₂, which is known to provide the desired [2R,(S)R]-β-

hydroxysulfoxide

8 in 86% yield and excellent dia-

stereomeric excess (Ͼ98%; Scheme 4).^[28]In this case the

benzyloxy group is syn to the bulky substituent (p-tolyl

group) of the sulfoxide.

Scheme 4. Synthesis of the β-hydroxysulfoxide derivative 8

Table 2 summarizes the results obtained in the palla-

dium-catalyzed Suzuki coupling of 2-methoxy-1-naph-

thylboronic acid (4)^[20]and the enantiopure iodophenyl-

containing β-hydroxysulfoxide 8.

A remarkable stereocontrol (dr = 98:2)^[29]was obtained

with a combination of dppf and Pd(OAc)₂in dioxane or

Scheme 3. Synthesis of the β-keto sulfoxide derivatives 1–3

The Pd-catalyzed Suzuki cross-couplings took place with THF, with a yield of 70% in dioxane at reflux (Table 2, en-

[24]

Pd(OAc)₂

in the presence of a phosphane [PPh₃, dppf, tries 1 and 2). Use of racemic BINAP or 2-(di-tert-butyl-

racemic BINAP, (R)-BINAP, 2-(di-tert-butylphosphanyl)bi- phosphanyl)biphenyl(Ligand A) did not provide any coup-

Table 2. Suzuki reactions of 8 with 2-methoxynaphthylboronic acid (4)

Entry^[a]

Solvent

Ligand

Biaryl 11

dr^[b]

Starting material

yield (%)

Reduction product

yield (%)

yield (%)^[c]

1

2

3

4

5

dioxane

THF

dioxane

dppf

BINAP

A

70

50

0

50

97:3

98:2

9

33

85

Ͼ85

50

20

17

Ͻ15

B

15:85

0

[a] Reaction conditions: 8 (1 equiv.), 4 (2 equiv.), Pd(OAc)₂(10 mol%), bidentate ligand (15 mol%), monodentate ligand (30 mol%), CsF

1

(4 equiv.), 70 °C, 3–5 h. [b] Determined by H NMR spectroscopy of the crude mixtures. [c] Yield of product isolated after chromatog-

raphy.

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1115

P.-E. Broutin, F. Colobert

FULL PAPER

Scheme 5. Synthesis of the protected β-hydroxysulfoxide derivatives 11, 12, 13, 15, and 23

ling product. Surprisingly, 1,3-bis(2,6-diisopropylphenyl) this case a side-product of elimination 16 was obtained in

imidazolidine(Ligand B) gave the coupling product with 48% yield). Compound 15, with an acetoxy group, was ob-

opposite axial chirality (dr = 15:85; Table 2, entry 5). How- tained in 99% yield upon treatment with Ac₂O and DMAP

ever, we also observed the hydrodehalogenation of the aryl in pyridine (Scheme 5).

iodide (20% in the case of the coupling reaction performed

Table 3 summarizes the results obtained in the palla-

in dioxane). Either the free hydroxy group or the acidic pro- dium-catalyzed Suzuki coupling of 2-methoxy-1-naph-

tons of the boronic acid might be responsible for the re- thylboronic acid (4)^[20]and the protected aryl iodides 12–15.

duction of the aryl halide. Thus, we first protected the hy- With methoxy, benzyloxy, and acetoxy derivatives, excellent

droxy group of the β-hydroxysulfoxide derivatives as a yields and diastereomeric excess were obtained in only one

methoxy by treatment with NaH and methyl iodide in hour (Table 3, entries 1, 3, 4). No trace of the other dia-

1

DMF at –20 °C to give 12 in 93% yield starting from the stereomer was detected by H and ¹³C NMR spectroscopy.

iodide, and 13 in 90% yield and 23 in 99% yield starting Starting from the bromide 13 instead of the iodide, the re-

from the corresponding bromides. We also protected the hy- sults were also excellent (Table 3, entry 2). Changing the

droxy group as a benzyloxy by treatment with benzyl chlo- ligand from dppf to PPh₃afforded the coupling product in

ride under the same conditions to give 14 in 52% yield (in a slightly lower yield (93%) but still with excellent diastereo-

Table 3. Suzuki reactions of phenyl-halide-containing protected β-hydroxy derivatives 12–15 with 2-methoxynaphthylboronic acid (4)

Entry^[a]

Halide

Pd(OAc)₂

(mol%)

Ligand

Biaryl, yield

(%)

dr^[b]

(%)

1

2

3

4

5

6

7

8

12

13

14

15

12

10

3

dppf

PPh₃

17, 99

17, 98

18, 97

19, 99

17, 93

17, 68

17, 0

Ͼ99:1

–

2

1

[a] Reaction conditions: 12–15 (1 equiv.), 4 (2 equiv.), Pd(OAc)₂(x mol%), bidentate ligand (1.5x mol%), monodentate ligand (3x mol%),

1

CsF (4 equiv.), 110 °C, 1 h. [b] Determined by H NMR spectroscopy of the crude mixtures.

1116

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Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

Scheme 6. Synthesis of the boronic esters 25, 27, and 28

selectivity (Table 3, entry 5). We also tried to decrease the Scope of the Palladium-Catalyzed Suzuki Coupling

amount of catalyst; 3 mol% Pd(OAc)₂with 9 mol% Reaction with Aryl-Halide-Containing Protected β-

PPh₃was sufficient to obtain the same yield and selectivity. Hydroxysulfoxides

With smaller quantities the yield of coupling product de-

creased, and with 1 mol% Pd(OAc)₂and 3 mol% PPh₃no

reaction occurred (Table 3, entries 6–8).

Table 4 summarizes the results obtained in the palla-

dium-catalyzed Suzuki coupling of various boronic acids^[31]

To investigate the scope of this method, and in order to (4, 24, and 26) or esters^[32](25, 27, and 28) with β-methoxy-

avoid the reductive hydrodehalogenation, we synthesized, in sulfoxide derivatives 12 and 20–23.

good yields, the boronic esters 25, 27, and 28 by condensa-

tion of ethylene glycol with the corresponding boronic acids ronic acid (24) occurred with excellent yield and diastereo-

in the presence of CaH₂in refluxing THF^[30](Scheme 6).

selectivity (Table 4, entry 1). Starting from the bromide 22,

The coupling reaction of 12 with 2-methyl-1-naphthylbo-

Table 4. Suzuki coupling reactions between β-methoxysulfoxide derivatives 12 and 20–23 and boronic acids 4, 24, and 26 or boronic

esters 25, 27, and 28

Entry^[a]

Halide

Boronic

derivative

Ligand

dppf^[d]

Biaryl, yield^[b]

(%)

dr^[c]

1

2

3

4

5

12

20

21

23

22

24

25

27

28

25

27

26

28

25

27

28

4

29 99

30 88

31 82

32 89

33 86

34 86

35 80

35 95

36 88

37 75

38 75

39 93

40 84

Ͼ99:1

90:10

75:25

80:20

95:5

90:10

85:15

75:25

80:20

Ͼ99:1

[e]

PPh_3[e]

PPh₃

6

7^[f]

8^[f]

9

dppf^[d]

[e]

10

11

12

13

PPh_3[e]

PPh₃

24

[a] Reaction conditions: 12, 20–23 (1 equiv.), 4, 24–28 (2 equiv.), CsF (4 equiv.), reflux dioxane, 1 h. [b] Isolated product after chromatog-

1

raphy. [c] Determined by H NMR spectroscopy on the crude mixture. [d] Pd(OAc)₂(10 mol%), dppf (15 mol%). [e] Pd(OAc)₂(3 mol%),

PPh₃(9 mol%). [f] 70 °C.

Eur. J. Org. Chem. 2005, 1113–1128

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1117

P.-E. Broutin, F. Colobert

FULL PAPER

Scheme 7. Suzuki coupling between the sulfone 41 and 2-methoxy-1-naphthylboronic acid (4)

Scheme 8. Suzuki coupling between 44 and 4

with a nitro group in the para position, and 2-methoxy- of 44 with 2-methoxy-1-naphthylboronic acid (4). The

1-naphthylboronic acid (4) or 2-methyl-1-naphthylboronic coupling product 45 was obtained in 89% yield but only a

acid (24), the coupling products were obtained very ef- 55:45 diastereomeric ratio (Scheme 8). Reduction of 17 and

ficiently (Table 4, entries 12, 13). β-Methoxysulfoxide 23, 45 with Raney nickel^[34]gave two different diastereomers,

bearing a naphthyl moiety,gave good yields in the Suzuki thus indicating that the two coupling products have the

coupling with the boronic esters 25, 27, and 28 but control same configuration of the chiral axis (a pair of enantio-

of the axial chirality was slightly lower (up to 85:15 dr) meric biaryls would otherwise have been obtained).

(Table 4, entries 9–11). The coupling reaction between aryl

At the moment we are performing a number of experi-

iodides bearing a methoxy group in the ortho position (21) ments on specific substrates in order to understand this

or a methyl group in the ortho position (20) and phenyl- or high atropodiastereoselectivity and to investigate the sense

naphthylboronic acids or estersafforded the coupling prod- of the chiral induction. The results will be reported in due

ucts in very good yields and selectivities of up to 95:5 dr course.

(Table 4, entries 2–8).

The absolute structures of the compounds 38 and 11

In order to determine the relative contribution of both were determined by X-ray crystallographic analysis.^[35]In

stereogenic centers to the asymmetric induction of the the case of the coupling reaction between 23 and 28, the

coupling reaction, we oxidized the sulfoxide into the corre- absolute configuration of the major diastereomer of 38 is

sponding sulfone 41. The coupling reaction of sulfone de- [aS,2R,(S)R] with the aromatic methoxy in front (Figure 1).

rivative 41 with 2-methoxy-1-naphthylboronic acid (4) af- NOESY correlations were in agreement with the solid-state

forded the corresponding coupling product 42 in 82% yield structure experiment, with a correlation between the aro-

and an 85:15 diastereomeric ratio (Scheme 7). Thus, oxi- matic methoxy and the aromatic hydrogen from the p-tolyl,

dation of the coupling product 17,^[33]obtained as a single

atropodiastereomer, was performed and, as expected, we

obtained exactly the same ¹H NMR spectra as the ¹H

NMR spectra of the major atropoisomer 42. This result in-

dicates that the diastereoselectivity of the coupling reaction

is mainly controlled by the stereogenic benzylic carbon

atom, which is closer to the biaryl C–C bond.

We also synthesized the [2S,(S)R]-β-hydroxysulfoxide 43,

the epimer of 8 at the stereogenic carbon atom, by dia-

stereoselective reduction of the β-keto sulfoxide 1 with DI-

BAL only. Here, the hydroxy group is anti to the bulky sub-

stituent of the sulfoxide. After protection of the hydroxy

group as methoxy (44), we performed the coupling reaction relations (right) of biaryl [aS,1R,(S)R]-38

Figure 1. X-ray crystal structure (left) and NOESY experiment cor-

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Eur. J. Org. Chem. 2005, 1113–1128

Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

and a correlation between H²and the ortho aromatic hydro-

gen of the phenyl moiety.

In the case of the coupling reaction between 8 and 4 in

the presence of ligand B, single crystals of the major dia-

stereomer 11 revealed that the chiral axis was aS with the

naphthylic methoxy in front (Figure 2). NOESY experi-

ments confirmed this configuration, with a correlation be-

tween the H²and the rear-facing naphthyl hydrogen, as well

as a correlation between the OH and the naphthyl hydrogen

H⁸. Thus, using dppf or PPh₃in this coupling reaction gave

the coupling product with an aR chiral axis and the naph-

thylic methoxy at the back. The agreement between the

NOESY correlations and the solid-state structure allowed

us to deduce the absolute configuration of all the major

biaryl products formed from NOESY experiments (see Sup-

porting Information and Scheme 9).

Figure 2. X-ray crystal structure (left) and NOESY experiment cor-

relations (right) of biaryl [aS,1R,(S)R]-11

binaphthyl, and phenylnaphthyl derivatives with an excel-

lent control of the axial chirality and excellent yield. A 1,3-

chirality induction from a stereogenic benzyloxy group to

the chiral axis is mainly responsible for the atropodiastereo-

selectivity. This methodology provides an efficient catalytic

access to axially chiral biaryls bearing a benzylic stereocen-

ter. The synthesis of the biaryl part of Vancomycin as well

Conclusions

We have performed a new atropodiastereoselective Su- as the synthesis of Steganacin using this methodology will

zuki coupling reaction that allows the synthesis of biphenyl, be reported in due course.

Scheme 9. Absolute configuration of the major biaryl compounds obtained in the presence of PPh₃or dppf

Eur. J. Org. Chem. 2005, 1113–1128

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1119

P.-E. Broutin, F. Colobert

FULL PAPER

(+)-[(S)R]-2-[2-(Dimethylamino)phenylsulfinyl]-1-(2-iodophenyl)-

ethanone (3): Orange oil (24% yield). R_f= 0.53 (EtOAc/hexanes,

Experimental Section

1

1:1). [α]²_D⁰= +252 (c = 1, CHCl₃). H NMR (CDCl₃, 200 MHz): δ

General Remarks: Unless otherwise specified, materials were pur-

chased from commercial suppliers and used without further purifi-

cation. THF, diethyl ether, and dioxane were distilled from sodium/

benzophenone immediately before use. Triethylamine and diisopro-

pylamine were distilled from calcium hydride and stored over po-

tassium hydroxide. Moisture-sensitive reactions were conducted in

oven- or flame-dried glassware under an argon atmosphere. All re-

actions were stirred magnetically and monitored by thin-layer

chromatography using precoated silica gel (60 F 254) plates. Col-

umn chromatography was performed with the indicated solvents

using silica gel-60. NMR spectra were recorded at room tempera-

ture using CDCl₃(δ = 7.26 ppm) as the reference (Bruker AC-200,

Bruker Avance 300 and Bruker Avance 400, ¹H at 200, 300 and

400 MHz and ¹³C at 50, 75 and 100 MHz, respectively). Chemical

shifts are expressed in ppm and coupling constants (J) in hertz.

Optical rotations were determined with a Perkin–Elmer 241 MC

polarimeter operating at the sodium D line at 20 °C. IR were re-

= 2.68 (s, 6 H, NMe₂), 4.53 (AB, J_A,B= 13.4 Hz, ∆ν = 75 Hz, 2

H, CH₂), 7.06–7.16 (m, 2 H, H_ar), 7.22–7.52 (m, 4 H, H_ar), 7.82–

7.93 (m, 2 H, H_ar) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ = 44.6

(NMe₂), 64.1 (CH₂), 91.6 (CH_ar), 119.8 (CH_ar), 124.6 (CH_ar), 125.2

(CH_ar), 128.1 (CH_ar), 129.7 (CH_ar), 131.9 (CH_ar), 132.3 (CH_ar),

136.7 (C_ar), 140.7 (C_ar), 142.5 (C_ar), 150.5 (C_ar), 194.7 (CO) ppm.

General Procedure for the Synthesis of Aryl Halides Bearing a β-

Hydroxysulfoxide: A solution of the corresponding β-keto sulfoxide

(15.6 mmol, 1 equiv.) and dry zinc bromide in THF (5 mL) was

stirred at room temp. for 15 min and then cooled to –78 °C. DI-

BALH (1 m in toluene) (31.23 mmol, 2 equiv.) was added dropwise,

the resulting mixture was stirred at –78 °C for 5 h, and then

quenched by addition of a saturated solution of sodium tartrate.

The resulting mixture was vigorously stirred until the phases were

easily separated. The aqueous layer was then extracted with EtOAc

and the combined organic layers were dried over Na₂SO₄, filtered,

and evaporated under reduced pressure. The crude product was

purified by flash chromatography.

corded with a Perkin–Elmer Spectum One spectrophotometer; ν

˜

values are quoted in cm^–1. X-ray diffraction data collection was

carried out with a Kappa CCD diffractometer equipped with an

Oxford liquid N₂device, using graphite-monochromatised Mo-K_α

radiation. Diffraction data were corrected for absorption and ana-

lysed using the OpenMolEn package.^[36]All non-H atoms were re-

fined anisotropically.

(–)-[1R,(S)R]-1-(2-Iodophenyl)-2-(p-tolylsulfinyl)ethanol (8): White

solid (86% yield; 5.2 g, 13.4 mmol; de Ͼ 98%); R_f= 0.3 (EtOAc/

hexanes, 1:1). M.p. 169–173 °C. [α]²_D⁰= –76 (c = 1, CHCl₃). IR

(neat): ν = 3308, 2919, 1583, 1596, 1563, 1493, 1459, 1437, 1399,

˜

1338, 1309, 1221, 1195, 1111, 1071, 1083, 1024, 1010, 987, 910,

835, 808, 760, 735. H NMR (CDCl₃, 300 MHz): δ = 2.41 (s, 3 H,

General Procedure for the Preparation of Aryl Halides Bearing a β-

Keto Sulfoxide (1–3): A solution of nBuLi (1.6 m in hexane,

8.0 mmol, 2 equiv.) was added at –15 °C to a solution of diisopro-

pylamine (8.0 mmol, 2 equiv.) in anhydrous THF (20 mL). After

30 min at –15 °C the reaction mixture was warmed to 0 °C and a

solution of sulfoxide (8.0 mmol, 2 equiv.) in THF (20 mL) was

added. After 30 min the lithiated anion was added dropwise by

cannula at 0 °C to a solution of 2-iodo-1-methyl benzoate

(4.0 mmol, 1 equiv.) in THF (20 mL). The resulting mixture was

warmed to room temp. and after 4 h was hydrolyzed at 0 °C by

addition of a saturated solution of NH₄Cl and acidified to pH 2

with 5% H₂SO₄. The aqueous layer was extracted with EtOAc. The

combined organic layers were then washed with brine, dried with

MgSO₄, and evaporated under reduced pressure. The crude product

was purified by flash chromatography over silica gel.

1

CH₃), 3.02 (AB part of an ABX system, J_A,B= 13.2, J_A,X= 10.1,

J_B,X= 1.6 Hz, ∆ν = 70 Hz, 2 H, CH₂), 4.64 (br. s, 1 H, OH), 5.57

[X part of an ABX system (br. d), J_A,X= 10.1 Hz, 1 H, CH(OH)],

6.97 (td, J = 7.8, 1.7 Hz, 1 H, H_ar), 7.37 (br. t, J = 7.8 Hz, 1 H,

H_ar), 7.49 (A₂B₂, J_A,B= 7.9 Hz, ∆ν = 73 Hz, 4 H, H_ar), 7.61 (dd,

J = 7.8, 1.7 Hz, 1 H, H_ar), 7.78 (dd, 1 H, J = 7.8 Hz, H_ar) ppm.

¹³C NMR (CDCl₃, 75 MHz): δ = 21.4 (CH₃), 62.4 (CH₂), 75.1

[CH(OH)], 96.4 (C_ar), 123.9 (CH_ar), 127.5 (CH_ar), 128.8 (CH_ar),

129.7 (CH_ar), 130.2 (CH_ar), 139.3 (CH_ar), 140.4 (C_ar), 142.2 (C_ar),

143.5 (C_ar) ppm. C₁₅H₁₅IO₂S (386.25): calcd. C 46.64, H 3.91, S

8.3; found C 46.66, H 3.98, S 8.4.

(+)-[1S,(S)R]-1-(2-Iodophenyl)-2-(p-tolylsulfinyl)ethanol (43): White

solid (90% yield; de Ͼ 98%); R_f= 0.47 (EtOAc/hexanes, 1:2). M.p.

127–128 °C. [α]²_D⁰= +173.1 (c = 1, CHCl ). IR (neat): ν = 3264,

˜

(+)-[(S)R]-1-(2-Iodophenyl)-2-(p-tolylsulfinyl)ethanone (1): Yellow

solid (82% yield). R_f= 0.55 (EtOAc). M.p. 65–68 °C. [α]²_D⁰= +133.1

3

1596, 1584, 1563, 1492, 1459, 1436, 1315, 1197, 1110, 1084, 1068,

1

1028, 1009, 808, 756. H NMR (CDCl₃, 300 MHz): δ = 2.45 (s, 3

(c = 1, CHCl ). IR (neat): ν = 3463, 3053, 2920, 1682, 1595, 1579,

˜

3

H, CH₃), 3.00 (AB part of an ABX system, J_A,B= 13.9, J_A,X

=

1493, 1462, 1426, 1398, 1378, 1284, 1254, 1191, 1117, 1084, 1056,

1

1.9, J_B,X= 9.8 Hz, ∆ν = 126 Hz, 2 H, CH₂), 5.10 (d, J = 1.9 Hz, 1

H, OH), 5.33 [X part of an ABX system (br. dt), J_A,X= 1.9, J_B,X

= 9.8 Hz, 1 H, CH(OH)], 6.96 (td, J = 7.8, 1.8 Hz, 1 H, H_ar), 7.39

(m, 1 H, H_ar), 7.51 (A₂B₂, J_A,B= 8.4 Hz, ∆ν = 69 Hz, 4 H, H_ar),

7.69 (br. dd, J = 7.8, 1.4 Hz, 2 H, H_ar) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 21.5 (CH₃), 57.2 (CH₂), 73.4 [CH(OH)], 95.8 (C_ar),

124.7 (CH_ar), 128.1 (CH_ar), 128.8 (CH_ar), 129.6 (CH_ar), 130.2

(CH_ar), 137.9 (C_ar), 139.3 (CH_ar), 142 (C_ar), 143.5 (C_ar) ppm.

C₁₅H₁₅IO₂S (386.25): calcd. C 46.64, H 3.91, S 8.3; found C 46.8,

H 3.89, S 8.36.

1016, 984, 812, 757. H NMR (CDCl₃, 300 MHz): δ = 2.4 (s, 3 H,

CH₃), 4.46 (AB, J_A,B= 13.9 Hz, ∆ν = 58 Hz, 2 H, CH₂), 7.14 (ddd,

J = 7.9, 6.1, 2.9 Hz, 1 H, H_ar), 7.37–7.44 (m, 2 H, H_ar), 7.45 (A₂B,

J_A,B= 8 Hz, ∆ν = 82 Hz, 4 H, H_ar), 7.91 (br. d, J = 7.9 Hz, 1 H,

H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.4 (CH₃), 68.0

(CH₂), 91.6 (C_ar), 124.4 (CH_ar), 128.2 (CH_ar), 129.6 (CH_ar), 130.1

(CH_ar), 132.7 (CH_ar), 139.9 (C_ar), 140.9 (CH_ar), 142.3 (C_ar), 142.3

(C_ar), 194.7 (CO) ppm.

(–)-[(S)S]-2-(tert-Butylsulfinyl)-1-(2-iodophenyl)ethanone (2): Yellow

oil (66% yield). R_f= 0.32 (EtOAc/hexanes, 9:1). [α]²_D⁰= –140.2 (c

= 0.94, CHCl ). IR (neat): ν = 2963, 2868, 1693, 1581, 1560, 1462,

General Procedure for the Synthesis of Aryl Halides Bearing a β-

˜

3

1429, 1392, 1362, 1288, 1246, 1189, 1134, 1039, 987, 885, 789, 749. Methoxysulfoxide: NaH (60%; 6 mmol, 1.2 equiv.) was washed with

¹H NMR (CDCl₃, 200 MHz): δ = 1.32 (s, 9 H, tBu), 4.07 (s, 2 H, hexane. A solution of the β-hydroxysulfoxide (5 mmol, 1 equiv.) in

CH₂), 7.17 (td, J = 7.8, 1.6 Hz, 1 H, H_ar), 7.47 (td, J = 7.8, 1.7

DMF (3 mL) was added at –20 °C to a suspension of NaH in DMF

Hz, 1 H, H_ar), 7.63 (dd, J = 7.8, 1.7 Hz, 1 H, H_ar), 7.95 (br. d, J (2 mL). After 30 min, methyl iodide (2 mmol, 2 equiv.) was added.

= 7.8 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ = 22.8

(tBu), 54.7 (CCH₃), 58.3 (CH₂), 91.4 (C_ar), 128.4 (CH_ar), 129.6

(CH_ar), 132.6 (CH_ar), 140.8 (CH_ar), 142.8 (C_ar), 196.4 (CO) ppm.

The resulting mixture was stirred for 1 h at –20 °C, quenched by

addition of a saturated solution of NH₄Cl, and extracted with

Et₂O. The combined organic layers were then dried with MgSO₄,

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Eur. J. Org. Chem. 2005, 1113–1128

Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

filtered, and the solvents evaporated. The crude product was puri-

fied by flash chromatography over silica gel.

142.9 (C_ar), 158.0 (C_ar) ppm. C₁₇H₁₉IO₃S (430.3): calcd. C 47.45,

H 4.45, S 7.45; found C 47.52, H 4.5, S 7.56.

(–)-[1R,(S)R]-1-Iodo-2-[1-methoxy-2-(p-tolylsulfinyl)ethyl]benzene

(+)-[1R,(S)R]-1-Bromo-2-[1-methoxy-2-(p-tolylsulfinyl)ethyl]-4-nitro-

(12): Colorless gum (98.4% yield). R_f= 0.32 (EtOAc/hexanes, 1:1). benzene (22): Colorless gum (93% yield). R_f= 0.29 (Et₂O). [α]²_D⁰

=

[α]²_D⁰= –13.7 (c = 1, CHCl₃). ¹H NMR (CDCl₃, 300 MHz): δ =

2.44 (s, 3 H, CH₃), 3.12 (2 H, AB part of an ABX system, J_A,B

13, J_A,X= 3.2, J_B,X= 10.2 Hz, ∆ν = 86 Hz, CH₂), 3.14 (s, 3 H,

OCH₃), 4.34 (1 H, X part of an ABX system, J_A,X= 3.2, J_B,X

+17.6 (c = 1, CHCl ). IR (neat): ν = 3093, 2928, 1606, 1573, 1525,

˜

3

=

1455, 1346, 1106, 1086, 1046, 1031, 982, 813, 741. ¹H NMR

(CDCl₃, 200 MHz): δ = 2.44 (s, 3 H, CH₃), 3.18 (AB part of an

ABX system, J_A,B= 13.3, J_A,X= 3.2, J_B,X= 9.3 Hz, ∆ν = 60 Hz,

2 H, CH₂), 3.19 (s, 3 H, OMe), 3.65 [X part of an ABX system, J_A,X

= 3.2, J_B,X= 9.2 Hz, 1 H, CH(OMe)], 7.5 (A₂B₂, J_A,B= 8.5 Hz, ∆ν

= 77 Hz, 4 H, H_ar), 7.7 (d, J = 8.8 Hz, 1 H, H_ar), 8.01 (dd, J = 8.8,

=

10.2 Hz, CH(OMe)], 6.99 (br. t, 1 Hd, J = 7.35, 2.07 Hz, H_ar), 7.4

(m, 1 H, H_ar), 7.43 (dd, J = 7.9, 2.0 Hz, 1 H7 Hz, H_ar), 7.51 (4 H,

A₂B₂, J_A,B= 8.3 Hz, ∆ν = 90 Hz, H_ar), 7.71 (dd, J = 7.9, 0.8 Hz,

1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.4 (CH₃), 56.7 2.7 Hz, 1 H, H_ar), 8.34 (d, J = 2.7 Hz, 1 H, H_ar) ppm. ¹³C NMR

(OCH₃), 63.5 (CH₂), 82.1 [CH(OMe)], 97.6 (C_ar), 124.8 (CH_ar),

(CDCl₃, 50 MHz): δ = 21.5 (CH₃), 57.4 (CH₂), 62.3 [CH(OMe)],

127.1 (CH_ar), 128.8 (CH_ar), 129.8 (CH_ar), 129.8 (CH_ar), 139.5 122.7 (CH_ar), 124.1 (CH_ar), 124.7 (CH_ar), 129.2 (C_ar), 130.0 (CH_ar),

(CH_ar), 140.0 (C_ar), 140.7 (C_ar), 141.8 (C_ar) ppm. C₁₆H₁₇IO₂S 134.2 (CH_ar), 140.0 (C_ar), 140.9 (C_ar), 142.1 (C_ar), 148.0 (C_ar) ppm.

(400.27): calcd. C 48.01, H 4.28, S 8.01; found C 48.11, H 4.34, S

(+)-[1R,(S)R]-1-Bromo-2-[1-methoxy-2-(p-tolylsulfinyl)ethyl]naph-

8.05.

thalene (23): White solid (99% yield). M.p. 79–81 °C; R_f= 0.26

(–)-[1R,(S)R]-1-Bromo-2-[1-methoxy-2-(p-tolylsulfinyl)ethyl]benzene

(13): Colorless oil (89.2% yield). R_f= 0.49 (Et₂O). [α]²_D⁰= –3 (c =

(EtOAc/hexanes, 1:1). [α]²_D⁰= +1.1 (c = 1, CHCl ). IR (neat): ν =

˜

3

3054, 2985, 2927, 1596, 1494, 1455, 1399, 1328, 1303, 1258, 1232,

1, CHCl ). IR (neat): ν = 2926, 1595, 1493, 1464, 1436, 1399, 1230, 1107, 1086, 1046, 997, 961, 821, 810, 749. ¹H NMR (CDCl₃,

˜

3

1207, 1117, 1104, 1086, 1047, 981, 808, 761. ¹H NMR (CDCl₃,

200 MHz): δ = 2.46 (s, 3 H, CH₃), 3.18 (s, 3 H, OCH₃), 3.25 (AB

300 MHz): δ = 2.44 (s, 3 H, CH₃), 3.16 (s, 3 H, CH₂), 3.18 (AB part of an ABX system, J_A,B= 13, J_A,X= 3.2, J_B,X= 9.9 Hz, ∆ν

part of an ABX system, J_A,B= 13.1, J_A,X= 3.2, J_B,X= 9.9 Hz, ∆ν

= 81 Hz, 2 H, CH₂), 3.16 (s, 3 H, OCH₃), 4.53 [X part of an ABX

system, J_A,X= 3.2, J_B,X= 9.9 Hz, 1 H, CH(OMe)], 7.15 (dt, J =

7.7, 1.6 Hz, 1 H, H_ar), 7.35 (m, 1 H, H_ar), 7.47 (dd, J = 7.7, 1.6

Hz, 1 H, H_ar), 7.47 (dd, J = 8.0, 1.3 Hz, 1 H, H_ar), 7.5 (A₂B₂, J_A,B

= 8.3 Hz, ∆ν = 86 Hz, 4 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz):

δ = 21.5 (CH₃), 56.94 (OCH₃), 63.48 (CH₂), 77.79 [CH(OMe)],

= 106 Hz, 2 H, CH₂), 4.87 [X part of an ABX system, J_A,X= 3.2,

J_B,X= 9.9 Hz, 1 H, CH(OMe)], 7.54 (ddd, J = 8.3, 7.0, 1.3 Hz, 1

H, H_ar), 7.56 (A₂B₂, J_A,B= 9.04 Hz, ∆ν = 88 Hz, 4 H, H_ar), 7.58

(d, J = 8.7 Hz, 1 H, H_ar), 7.59 (ddd, J = 8.5, 7.0, 1.5 Hz, 1 H, H_ar),

7.82 (ddd, 1 H, J = 8.3, 1.5 Hz, H_ar), 7.85 (d, J = 8.7 Hz, 1 H,

H_ar), 8.24 (br. d, J = 8.5 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃,

50 MHz): δ = 21.5 (CH₃), 57.0 (OCH₃), 63.4 (CH₂), 78.5

122.51 (C_ar), 124.89 (CH_ar), 127.52 (CH_ar), 128.12 (CH_ar), 129.62 [CH(OMe)], 122.9 (C_ar), 123.8 (CH_ar), 124.9 (CH_ar), 127.0 (CH_ar),

(CH_ar), 129.94 (CH_ar), 133.04 (CH_ar), 138.18 (C_ar), 140.32 (C_ar), 127.2 (CH_ar), 127.7 (CH_ar), 128.2 (CH_ar), 128.7 (CH_ar), 129.9

141.99 (C_ar) ppm. C₁₆H₁₇BrO₂S (353.27): calcd. C 54.4, H 4.85, S

9.08; found C 54.2, H 4.9, S 8.93.

(CH_ar), 132.2 (C_ar), 134.4 (C_ar), 136.3 (C_ar), 140.4 (C_ar), 142.0 (C_ar)

ppm. C₂₀H₁₉BrO₂S (403.33): calcd. C 59.56, H 4.75, S 7.95; found

C 59.51, H 7.79, S 7.94.

(–)-[1R,(S)R]-1-Iodo-2-[1-methoxy-2-(p-tolylsulfinyl)ethyl]-6-meth-

ylbenzene (20): White solid (97% yield). R_f= 0.4 (Et₂O). M.p. 101–

(–)-[1R,(S)R]-2-[1-Benzyloxy-2-(p-tolylsulfinyl)ethyl]-1-iodobenzene

(14): Prepared by the same procedure as for the formation of aryl

halides bearing a β-methoxysulfoxide, with BnCl in place of MeI.

Colorless oil (52% yield; 190 mg, 0.4 mmol); R_f= 0.13 (EtOAc/n-

105 °C. [α]²_D⁰= –35.1 (c = 1, CHCl ). IR (neat): ν = 2920, 1571,

˜

3

1493, 1443, 1399, 1243, 1204, 1100, 1081, 1032, 1005, 980, 820,

795, 778. ¹H NMR (CDCl₃, 300 MHz): δ = 2.34 (s, 3 H, CH₃),

2.36 (s, 3 H, CH₃), 3.07 (AB part of an ABX system, J_A,B= 13,

J_A,X= 3, J_B,X= 10.2 Hz, ∆ν = 66 Hz, 2 H, CH₂), 3.07 (s, 3 H,

OCH₃), 4.42 [X part of an ABX system, J_A,X= 3, J_B,X= 10.2 Hz,

hexane, 2:1). [α]²_D⁰= –42.5 (c = 1, CHCl ). IR (neat): ν = 3056,

˜

3

3030, 2920, 2868, 1596, 1584, 1563, 1493, 1455, 1435, 1396, 1346,

1208, 1110, 1084, 1045, 1012, 808, 749, 737, 698. ¹H NMR (CDCl₃,

300 MHz): δ = 2.39 (s, 3 H, CH₃), 3.18 (AB part of an ABX system,

1 H, CH(OMe)], 7,08–7,22 (m, 3 H, H_ar), 7.44 (A₂B₂, J_A,B

=

8.1 Hz, ∆ν = 92 Hz, 4 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): J_A,B= 13, J_A,X= 2.9, J_B,X= 10.2 Hz, ∆ν = 100 Hz, 2 H, CH₂),

δ = 21.5 (CH₃), 29.5 (CH₃), 56.8 (OCH₃), 63.6 (CH₂), 83.1

4.28 (AB, J_A,B= 11.87 Hz, ∆ν = 93 Hz, 2 H, OCH₂Ph), 4.54 [X

[CH(OMe)], 105.1 (C_ar), 124.5 (CH_ar), 125.0 (CH_ar), 128.6 (CH_ar), part of an ABX system, J_A,X= 2.9, J_B,X= 10.17 Hz, 1 H,

129.7 (CH_ar), 129.9 (CH_ar), 140.3 (C_ar), 141.6 (C_ar), 141.9 (C_ar), CH(OBn)], 7.00 (td, J = 7.7, 1.7 Hz, 1 H, H_ar), 7.22–7.46 (m, 10

142.5 (C_ar) ppm. C₁₇H₁₉IO₂S (414.30): calcd. C 49.28, H 4.62, S

7.74; found C 49.31, H 4.68, S 7.8.

H, H_ar), 7.53 (dd, J = 7.7, 1.7 Hz, 1 H, H_ar), 7.76 (dd, J = 7.9, 1.1

Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.5 (CH₃),

64.0 (CH₂), 70.7 (OCH₂Ph), 79.4 [CH(OBn)], 97.5 (C_ar), 125.0

(CH_ar), 127.7 (CH_ar), 128.0 (CH_ar), 128.2 (CH_ar), 128.5 (CH_ar),

129.1 (CH_ar), 130.0 (CH_ar), 130.1 (CH_ar), 137.2 (C_ar), 139.7 (CH_ar),

140.4 (C_ar), 141.1 (C_ar), 141.8 (C_ar) ppm.

(–)-[1R,(S)R]-1-Iodo-6-methoxy-2-[1-methoxy-2-(p-tolylsulfinyl)eth-

yl]benzene (21): White solid (97% yield). R_f= 0.2 (Et₂O). M.p. 74–

75 °C. [α]²_D⁰= –22 (c = 1, CHCl ). IR (neat): ν = 2935, 1651, 1596,

˜

3

1585, 1567, 1493, 1463, 1427, 1398, 1286, 1264, 1108, 1084, 1040,

1014, 985, 808, 775. ¹H NMR (CDCl₃, 300 MHz): δ = 2.44 (s, 3

H, CH₃), 3.15 (s, 3 H, OCH₃), 3.15 (AB part of an ABX system,

J_A,B= 13.2, J_A,X= 3, J_B,X= 10.2 Hz, ∆ν = 74 Hz, 2 H, CH₂), 3.86

(+)-[(S)R]-1-Iodo-2-[2-(p-tolylsulfinyl)vinyl]benzene (16): Colorless

gum (48% yield; E/Z: Ͼ 99:1); R_f= 0.5 (EtOAc). [α]²_D⁰= +94 (c =

1, CHCl ). IR (neat): ν = 3051, 2920, 1595, 1580, 1492, 1458, 1432,

˜

3

(s, 3 H, OCH₃), 4.49 [X part of an ABX system, J_A,X= 3, J_B,X

=

1303, 1178, 1083, 1050, 1013, 958, 806. ¹H NMR (CDCl₃,

10.2 Hz, 1 H, CH(OMe)], 6.75 (dd, J = 8.3, 1.3 Hz, 1 H, H_ar), 7.07 200 MHz): δ = 2.39 (s, 3 H, CH₃), 6.71 (d, J = 15.3 Hz, 1 H,

(dd, J = 7.7, 1.3 Hz, 1 H, H_ar), 7.33 (br. t, 1 H, J = 8 Hz, H_ar),

CH=CH), 6.98 (t, J = 7.9 Hz, 1 H, H_ar), 7.27 (t, J = 7.9 Hz, 1 H,

H_ar), 7.39 (d, J = 7.9 Hz, 1 H, H_ar), 7.44 (A₂B₂, J_A,B= 8 Hz, ∆ν =

7.52 (A₂B₂, J_A,B= 8.1 Hz, ∆ν = 91 Hz, 4 H, H_ar) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ = 21.5 (CH₃), 56.5 (OCH₃), 56.8 (OCH₃), 63.5 78 Hz, 4 H, H_ar), 7.56 (d, J = 15.3 Hz, 1 H, CH=CH), 7.84 (d, J

(CH₂), 82.6 [CH(OMe)], 90.3 (C_ar), 110.6 (CH_ar), 119.5 (CH_ar),

= 7.9 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ = 21.4

125.1 (CH_ar), 129.9 (CH_ar), 129.9 (CH_ar), 140.3 (C_ar), 142.0 (C_ar), (CH₃), 100.2 (C_ar), 124.8 (CH_ar), 127.4 (CH_ar), 128.4 (CH_ar), 130.1

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P.-E. Broutin, F. Colobert

FULL PAPER

(CH_ar), 130.7 (CH_ar), 136.7 (CH_ar), 137.2 (C_ar), 139.4 (CH=CH),

139.9 (CH=CH), 140.4 (C_ar), 141.7 (C_ar) ppm.

General Procedure for the Synthesis of 1,3,2-Dioxaborolane: A sus-

pension of the boronic acid (5 mmol, 1 equiv.), ethylene glycol

(5 mmol, 1 equiv.), and CaH₂(10 mmol, 2 equiv.) in THF (10 mL)

was refluxed for 2 h. The reaction mixture was then cooled to room

temp., filtered through a pad of celite, and washed with EtOAc.

The crude product was used without any further purification.

(+)-[1R,(S)R]-1-(2-Bromophenyl)-2-(p-tolylsulfinyl)ethyl Acetate

(15): Acetic anhydride (50 µL, 0,57 mmol, 1.1 equiv.) was added

dropwise to a solution of β-hydroxysulfoxide 8 (200 mg, 0,52 mmol,

1 equiv.) and DMAP (catalytic amount) in pyridine (7 mL). The

resulting mixture was stirred for 2 h at room temp. and then

quenched by addition of a saturated solution of NH₄Cl. The aque-

ous phase was extracted with EtOAc. The combined organic layers

were dried over MgSO₄, filtered, and the solvents evaporated. The

crude product was purified by flash chromatography over silica gel

(Et₂O). Colorless oil (99% yield; 225 mg, 0.53 mmol); R_f= 0.32

2-(Naphthalen-1-yl)-1,3,2-dioxaborolane (25): White solid (99%

yield). M.p. 36–39 °C. IR (neat): ν = 2911, 1572, 1507, 1396, 1315,

˜

1

1255, 1200, 1135, 1050, 1030, 1015, 938, 803, 779, 747. H NMR

(CDCl₃, 300 MHz): δ = 4.48 (s, 4 H, CH₂), 7,48–7,56 (m, 3 H, H_ar),

7.86 (dd, J = 7.7, 1.5 Hz, 1 H, H_ar), 7.97 (d, J = 8.3 Hz, 1 H, H_ar),

8.12 (d, J = 6.8 Hz, 1 H, H_ar), 8.75 (d, J = 8.3 Hz, 1 H, H_ar) ppm.

¹¹B NMR (CDCl₃, 128.38 MHz): δ = 35.17 ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ = 65.9 (CH₂), 125.0 (CH_ar), 125.5 (CH_ar),

126.4 (CH_ar), 128.2 (CH_ar), 128.4 (CH_ar), 132.0 (CH_ar), 133.2 (C_ar),

136.1 (CH_ar), 136.8 (C_ar) ppm.

(Et₂O). [α]²_D⁰= +58.8 (c = 1, CHCl ). IR (neat): ν = 3054, 2922,

˜

3

1747, 1494, 1435, 1372, 1233, 1085, 1041, 1013, 977, 933, 880, 761,

731. ¹H NMR (CDCl₃, 300 MHz): δ = 2.108 [s, 3 H, OC(=O)CH₃],

2.42 (s, 3 H, CH₃), 3.26 (AB part of an ABX system, J_A,B= 13.4,

J_A,X= 3, J_B,X= 10.2 Hz, ∆ν = 47 Hz, 2 H, CH₂), 6.08 [X part of

an ABX system, J_A,X= 3, J_B,X= 10.2 Hz, 1 H, CH(OAc)], 6.98

(ddd, J = 7.9, 6.6, 2.5 Hz, 1 H, H_ar), 7.30–7.40 (m, 2 H, H_ar), 7.49

(A₂B₂, J_A,B= 8.5 Hz, ∆ν = 82 Hz, 4 H, H_ar), 7.76 (br. dd, J =

7.9, 1.5 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 20.8

[OC(=O)CH₃], 21.4 (CH₃), 62.5 (CH₂), 74.0 [CH(OAc)], 96.3 (C_ar),

124.6 (CH_ar), 126.9 (CH_ar), 128.8 (CH_ar), 130.1 (CH_ar), 130.1

(CH_ar), 139.8 (CH_ar), 140.3 (C_ar), 140.7 (C_ar), 142.1 (C_ar), 169.3

[OC(=O)CH₃] ppm.

1

2-o-Tolyl-1,3,2-dioxaborolane (27): Colorless oil (99% yield). H

NMR (CDCl₃, 300 MHz): δ = 2.55 (s, 3 H, CH₃), 4.37 [s, 4 H,

(OCH₂)₂], 7,15–7,21 (m, 2 H, H_ar), 7.34 (td, J = 7.5, 1.7 Hz, 1

H, H_ar), 7.81 (dd, J = 7.9, 1.7 Hz, 1 H, H_ar) ppm. ¹¹B (CDCl₃,

128.38 MHz): δ = 34.96 ppm. ¹³C NMR (CDCl₃, 75 MHz): δ =

22.3 (CH₃), 65.8 [(OCH₂)₂], 124.8 (CH_ar), 129.9 (CH_ar), 131.1

(CH_ar), 136.3 (CH_ar), 145 (C_ar) ppm.

2-(2-Methoxyphenyl)-1,3,2-dioxaborolane (28): White solid (99%

yield). M.p. 29–33 °C. IR (neat): ν = 2968, 1597, 1574, 1489, 1457,

˜

(–)-[1R,(S)R]-1-Iodo-2-[1-methoxy-2-(p-tolylsulfonyl)ethyl]benzene

(41): A solution of mCPBA (285 mg, 0.8 mmol, 2.2 equiv.) was

added to a solution of the β-methoxysulfoxide 12 (300 mg,

0.75 mmol, 1 equiv.) in CH₂Cl₂(15 mL). The resulting mixture was

stirred at room temp. for 6 h and then quenched by addition of a

1 m solution of NaOH (15 mL); the aqueous phase was then ex-

tracted with CH₂Cl₂. The organic layers were dried with MgSO₄,

filtered, and concentrated under reduced pressure. The crude pro-

duct was purified by flash chromatography over silica gel (EtOAc/

n-hexane, 1:4). Colorless oil (99% yield; 380 mg; 0.94 mmol). R_f=

0.22 (EtOAc/hexanes, 1:2). [α]²_D⁰= –80.1 (c = 1, CHCl₃). IR (neat):

1435, 1385, 1330, 1272, 1244, 1210, 1074, 1022, 943, 767. ¹H NMR

(CDCl₃, 300 MHz): δ = 3.88 (s, 3 H, OCH₃), 4.38 (s, 4 H, CH₂),

6.9 (br. d, 8.3 H, H_ar), 6.97 (td, J = 0.8 Hz, 7.4 H, H_ar), 7.44 (ddd,

J = 7.4, 1.9 Hz, 8.3 H, H_ar), 7.76 (dd, J = 1.7 Hz, 7.2 H, H_ar)

ppm. ¹¹B NMR (CDCl₃, 128.38 MHz): δ = 34.55 ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ = 55.58 (OCH₃), 65.85 (CH₂), 110.21 (CH_ar),

120.31 (CH_ar), 133.07 (CH_ar), 127.43 (CH_ar), 164.3 (C_ar) ppm.

General Procedure for the Suzuki Coupling Reaction: CsF

(151.8 mg, 1.0 mmol, 4 equiv.) was fused under vacuum in a two-

necked, round-bottomed flask. After cooling to room temperature,

the boronic acid 4 (100.9 mg, 0.5 mmol, 2 equiv.) and dry dioxane

(2.5 mL) were added under argon. The aromatic halide 12 (100 mg,

0.25 mmol, 1 equiv.), palladium acetate (1.68 mg, 0.007 mmol,

3 mol%), dppf (6.23 mg, 0.011, 4.5 mol%), and dry dioxane (5 mL)

were placed in a second round-bottomed flask under argon. This

second reaction mixture was stirred at room temperature for 30 min

and then added to the boronic acid 4 by cannula. This mixture was

stirred under argon at 80 °C for 1 h. It was then cooled to room

temperature, diluted with water (20 mL) and extracted with CH₂Cl₂

(2 × 20 mL). The organic layer was dried (MgSO₄) and the solvents

evaporated. The residue was purified by chromatography over silica

gel.

ν = 3060, 2984, 2929, 2827, 1733, 1597, 1461, 1434, 1301, 1243,

˜

1159, 1140, 1115, 1103, 1013, 987, 818. ¹H NMR (CDCl₃,

300 MHz): δ = 2.46 (s, 3 H, CH₃), 3.17 (s, 3 H, OCH₃), 3.36 [AB

part of an ABX system (m), 2 H, CH₂], 4.94 [X part of an ABX

system, J_A,X= 5.6, J_B,X= 6.8 Hz, 1 H, CH(OMe)], 6.99 (ddd, J =

7.9, 5.6, 3.8 Hz, 1 H, H_ar), 7.30–7.38 (m, 2 H, H_ar), 7.6 (A₂B₂, J_A,B

= 8.3 Hz, ∆ν = 157 Hz, 4 H, H_ar), 7.8 (br. d, J = 7.9 Hz, 1 H, H_ar)

ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.6 (CH₃), 57.1 (OCH₃),

62.0 (CH₂), 81.7 [CH(OMe)], 97.6 (C_ar), 127.3 (CH_ar), 128.3

(CH_ar), 128.9 (CH_ar), 129.6 (CH_ar), 130.1 (CH_ar), 137.6 (CH_ar),

139.8 (C_ar), 140.6 (C_ar), 144.4 (C_ar) ppm.

(+)-[1S,(S)R]-1-Iodo-2-[1-methoxy-2-(p-tolylsulfinyl)ethyl]benzene

(44): White solid (99% yield). R_f= 0.35 (Et₂O). M.p. 79–82 °C.

(–)-[aR,1R,(S)R]-1-[2-(2-Methoxynaphthalen-1-yl)phenyl]-2-(p-to-

lylsulfinyl)ethanol (aR-11): Orange solid (64% yield). R_f= 0.15

(EtOAc/hexanes, 1:1). M.p. 60–64 °C. [α]²_D⁰= –101.6 (c = 1,

[α]²_D⁰= +26.1 (c = 1, CHCl ). IR (neat): ν = 3016, 1561, 1494, 1110,

˜

3

1098, 1038, 1030, 1018, 1009, 981, 801, 751. ¹H NMR (CDCl₃,

300 MHz): δ = 2.38 (s, 3 H, CH₃), 2.92 (AB part of an ABX system,

J_A,B= 13.2, J_A,X= 10.9, J_B,X= 2.4 Hz, ∆ν = 101 Hz, C2 H, H₂),

3.39 (s, 3 H, OCH₃), 5.05 [X part of an ABX system, J_A,X= 10.9,

CHCl ). IR (neat): ν = 3244, 1621, 1593, 1509, 1462, 1254, 1062,

˜

3

1

1019, 1010, 802, 759, 746, 729. H NMR (CDCl₃, 200 MHz): δ =

2.33 (s, 3 H, CH₃), 2.71 (AB part of an ABX system, J_A,B= 13.2,

J_B,X= 2.4 Hz, 1 H, CH(OMe)], 6.98 (td, J = 7.7, 1.8 Hz, 1 H, H_ar), J_A,X= 10.5, J_B,X= 1.9 Hz, ∆ν = 191 Hz, 2 H, CH₂), 3.61 (br. s, 1

7.36 (td, J = 7.7, 1.1 Hz, 1 H, H_ar), 7.44 (dd, J = 7.7, 1.8 Hz, 1 H, H, OH), 3.81 (s, 3 H, OMe), 4.82 [X part of an ABX system, J_A,X

H_ar), 7.43 (A₂B₂, J_A,B= 8.1 Hz, ∆ν = 85 Hz, 4 H, H_ar), 7.8 (dd, = 10.5, J_B,X= 1.9 Hz, 1 H, CH(OH)], 6.88 (A₂B₂, J_A,B= 8.3 Hz,

J = 7.7, 1.1 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = ∆ν = 35 Hz, 4 H, H_ar), 7.09 (d, J = 8.3 Hz, 1 H, H_ar), 7.14 (dd, J

21.3 (CH₃), 57.4 (OCH₃), 64.8 (CH₂), 80.7 [CH(OMe)], 97.7 (C_ar),

= 7.5, 1.3 Hz, 1 H, H_ar), 7.27 (ddd, J = 8.3, 5.6, 1.3 Hz, 1 H, H_ar),

123.9 (CH_ar), 127.2 (CH_ar), 128.8 (CH_ar), 129.9 (CH_ar), 129.9 7.33 (d, J = 9 Hz, 1 H, H_ar), 7.39 (td, J = 8.3, 1.1 Hz, 1 H, H_ar),

(CH_ar), 139.9 (CH_ar), 141.1 (C_ar), 141.4 (C_ar), 141.6 (C_ar) ppm. 7.4 (td, J = 7.5, 1.3 Hz, 1 H, H_ar), 7.48 (td, J = 7.7, 1.1 Hz, 1 H,

C₁₆H₁₇IO₂S (400.27): calcd. C 48.01, H 4.28, S 8.01; found C 48.17,

H 4.36, S 8.14.

H_ar), 7.79 (br. d, J = 7.8 Hz, 1 H, H_ar), 7.88 (d, J = 8.3 Hz, 1 H,

H_ar), 7.92 (d, J = 9 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃,

1122

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Eur. J. Org. Chem. 2005, 1113–1128

Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

50 MHz): δ = 21.3 (CH₃), 56.4 (OMe), 64.3 (CH₂), 68.3 [CH(OH)], (–)-[aR,1R,(S)R]-1-{2-[1-Benzyloxy-2-(p-tolylsulfinyl)ethyl]phenyl}-

113.2 (CH_ar), 122.1 (C_ar), 123.3 (CH_ar), 123.5 (CH_ar), 124.4 (CH_ar), 2-methoxynaphthalene (aR-18): Orange solid (97% yield; dr Ͼ 99:1);

125.4 (CH_ar), 126.7 (CH_ar), 127.7 (CH_ar), 128.0 (CH_ar), 128.2 R_f= 0.25 (Et₂O). M.p. 47–49 °C. [α]²_D⁰= –94 (c = 1, CHCl₃). IR

(CH_ar), 128.9 (C_ar), 129.4 (CH_ar), 129.5 (CH_ar), 130.9 (CH_ar), 133.4 (neat): ν = 2922, 1621, 1593, 1508, 1454, 1380, 1332, 1265, 1253,

˜

1

(C_ar), 133.7 (C_ar), 139.5 (C_ar), 141.1 (C_ar), 141.5 (C_ar), 153.0 (C_ar) 1068, 1040, 806, 747, 697. H NMR (CDCl₃, 300 MHz): δ = 2.39

ppm. C₂₆H₂₄O₃S (416.53): calcd. C 74.97, H 5.81, S 7.7; found C

74.73, H 5.79, S 7.77.

(s, 3 H, CH₃), 2.46 (X part of an ABX system, J_A,X= 12.8, J_B,X=

2.4 Hz, 1 H, CH₂), 3.68 [AB part of an ABX system, J_A,B= 11.2,

J_A,X= 12.8, J_B,X= 2.4 Hz, ∆ν = 134 Hz, 2 H, CH(OBn) + CH₂],

3.7 (s, 3 H, OMe), 4.25 (AB, J_A,B= 11.8 Hz, ∆ν = 135 Hz, 2 H,

CH₂Ph), 6.76 (A₂B₂, J_A,B= 8.2 Hz, ∆ν = 33 Hz, 4 H, H_ar), 7.04

(br. d, J = 8.1 Hz, 1 H, H_ar), 7.11 (dd, J = 7.4, 1.5 Hz, 1 H, H_ar),

7.12 (d, J = 9 Hz, 1 H, H_ar), 7.33 (m, 1 H, H_ar), 7.33–7.43 (m, 5

H, H_ar), 7.4 (m, 1 H, H_ar), 7.44 (td, J = 7.4, 1.5 Hz, 1 H, H_ar), 7.53

(td, J = 7.4, 1.5 Hz, 1 H, H_ar), 7.79 (dd, 1 H, J = 7.8 Hz, H_ar),

8.84 (d, J = 9 Hz, 1 H, H_ar), 8.85 (br. d, J = 7.4 Hz, 1 H, H_ar)

ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.5 (CH₃), 55.8 (CH), 70.5

(CH₂), 74.9 (CH₂), 112.2 (CH_ar), 121.6 (C_ar), 123.8 (CH_ar), 124.0

(CH_ar), 124.5 (CH_ar), 125.7 (CH_ar), 127.1 (CH_ar), 127.3 (CH_ar),

127.6 (CH_ar), 127.9 (CH_ar), 128.1 (CH_ar), 128.4 (CH_ar), 128.5

(CH_ar), 128.9 (C_ar), 129.4 (CH_ar), 129.5 (CH_ar), 131.2 (CH_ar), 133.6

(C_ar), 135.2 (C_ar), 138.2 (C_ar), 138.9 (C_ar), 140.9 (C_ar), 152.3 (C_ar)

ppm.

(–)-[aS,1R,(S)R]-1-[2-(2-Methoxynaphthalen-1-yl)phenyl]-2-(p-tolyl-

sulfinyl)ethanol (aS-11): White cristals; R_f= 0.15 (EtOAc/hexanes,

1:1). M.p. 211–213 °C. [α]²_D⁰= –3.8 (c = 1, CHCl₃). ¹H NMR

(CDCl₃, 200 MHz): δ = 2.39 (s, 3 H, CH₃), 3.03 (AB part of an

ABX system, J_A,B= 13.1, J_A,X= 9.8, J_B,X= 2.3 Hz, ∆ν = 37 Hz,

2 H, CH₂), 3.77 (s, 3 H, OMe), 3.78 (d, J = 1.9 Hz, 1 H, OH), 4.84

[X part of an ABX system (br. d), J_A,X= 9.8 Hz, 1 H, CH(OH)],

7.1–7.54 (m, 11 H, H_ar), 7.76–7.96 (m, 3 H, H_ar) ppm. ¹³C NMR

(CDCl₃, 50 MHz): δ = 21.4 (CH₃), 56.2 (OMe), 63.9 (CH₂), 68.8

[CH(OH)], 112.8 (CH_ar), 122.5 (C_ar), 123.5 (CH_ar), 123.9 (CH_ar),

124.7 (CH_ar), 126.0 (CH_ar), 127.0 (CH_ar), 127.8 (CH_ar), 127.9

(CH_ar), 128.4 (CH_ar), 128.9 (C_ar), 129.8 (CH_ar), 129.9 (CH_ar), 131.0

(CH_ar), 133.3 (C_ar), 133.7 (C_ar), 140.4 (C_ar), 141.3 (C_ar), 141.6 (C_ar),

153.5 (C_ar) ppm.

(–)-[aR,1R,(S)R]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfinyl)-

ethyl]phenyl}naphthalene (aR-17): White solid (99% yield). R_f= 0.2

(–)-[aR,2R,(S)R]-1-[2-(2-Methoxynaphthalen-1-yl)phenyl]-2-(p-to-

lylsulfinyl)ethyl Acetate (aR-19): White solid (99% yield; dr Ͼ 99:1);

R_f= 0.32 (EtOAc/hexanes, 2:1). M.p. 45–48 °C. [α]²_D⁰= –58.4 (c =

(Et₂O). M.p. 43–46 °C. [α]²_D⁰= –138 (c = 1, CHCl ). IR (neat): ν =

˜

3

1

2934, 1593, 1508, 1463, 1266, 1254, 1085, 1041, 807, 761, 750. H

1, CHCl ). IR (neat): ν = 2935, 1620, 1593, 1508, 1370, 1257, 1224,

˜

NMR (CDCl₃, 300 MHz): δ = 2.35 (X part of an ABX system,

J_A,X= 12.2, J_B,X= 2.4 Hz, 1 H, CH₂), 2.37 (s, 3 H, CH₃), 3.11 [s,

3 H, CH(OCH₃)], 3.48 [AB part of an ABX system, J_A,B= 11.3,

J_A,X= 12.2, J_B,X= 2.4 Hz, ∆ν = 78 Hz, 2 H, CH₂, CH(OMe)],

3.63 (s, 3 H, OCH₃), 6.82 (A₂B₂, J_A,B= 8.1 Hz, ∆ν = 24 Hz, 4 H,

H_ar), 7.02 (br. d, J = 8.2 Hz, 1 H, H_ar), 7.06 (dd, J = 7.5, 1.2 Hz,

1 H, H_ar), 7.09 (d, J = 8.9 Hz, 1 H, H_ar), 7.3 (ddd, J = 8.2, 6.9, 1.4

Hz, 1 H, H_ar), 7.37 (ddd, J = 8.2, 6.9, 1.4 Hz, 1 H, H_ar), 7.38 (td,

J = 7.4, 1.4 Hz, 1 H, H_ar), 7.48 (td, J = 7.5, 1.4 Hz, 1 H, H_ar), 7.66

(dd, J = 7.8, 1.4 Hz, 1 H, H_ar), 7.82 (d, J = 8.9 Hz, 1 H, H_ar), 7.84

(br. d, J = 8.2 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ

= 21.4 (CH₃), 55.6 [CH(OCH₃)], 56.2 (OCH₃), 64.4 (CH₂), 76.1

[CH(OMe)], 112.1 (CH_ar), 121.4 (C_ar), 123.6 (CH_ar), 123.8 (CH_ar),

124.3 (CH_ar), 125.4 (CH_ar), 126.9 (CH_ar), 127.8 (CH_ar), 127.9

(CH_ar), 128.2 (CH_ar), 128.8 (C_ar), 129.3 (CH_ar), 129.3 (CH_ar), 131.1

(CH_ar), 133.5 (C_ar), 135.2 (C_ar), 138.6 (C_ar), 139.2 (C_ar), 140.8 (C_ar),

152.2 (C_ar) ppm. C₂₇H₂₆O₃S (430.56): calcd. C 75.32, H 6.09, S

8.34; found C 75.55, H 6.18, S 8.09.

3

1034, 1020, 806. ¹H NMR (CDCl₃, 300 MHz): δ = 2.08 (s, 3 H,

CH₃), 2.36 (s, 3 H, OAc), 2.92 (AB part of an ABX system, J_A,B

= 13.4, J_A,X= 11.1, J_B,X= 2.07 Hz, ∆ν = 180 Hz, 2 H, CH₂), 3.79

(s, 3 H, OMe_ar), 5.83 [X part of an ABX system, J_A,X= 11.1, J_B,X

= 2.07 Hz, 1 H, CH(OAc)], 6.87 (A₂B₂, J_A,B= 8.2 Hz, ∆ν = 26 Hz,

4 H, H_ar), 6.99 (br. d, J = 8.4 Hz, 1 H, H_ar), 7.11 (dd, J = 7.4, 1.6

Hz, 1 H, H_ar), 7.23 (d, J = 9 Hz, 1 H, H_ar), 7.24 (ddd, J = 8.4, 6.8,

1.4 Hz, 1 H, H_ar), 7.33 (ddd, J = 8.1, 6.8, 1.2 Hz, 1 H, H_ar), 7.4

(td, J = 7.4, 1.5 Hz, 1 H, H_ar), 7.46 (td, J = 7.4, 1.5 Hz, 1 H, H_ar),

7.64 (dd, J = 7.7, 1.6 Hz, 1 H, H_ar), 7.8 (br. d, J = 8.1 Hz, 1 H, H_ar),

7.82 (d, J = 9 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ

= 20.9 (CH₃), 21.4 (OCOCH₃), 56 (OMe), 64 (CH₂), 68.1

[CH(OAc)], 112.6 (CH_ar), 120.8 (C_ar), 123.3 (CH_ar), 123.4 (CH_ar),

124 (CH_ar), 125.5 (CH_ar), 126.7 (CH_ar), 127.9 (CH_ar), 128.1 (CH_ar),

128.2 (CH_ar), 128.6 (C_ar), 129.4 (CH_ar), 129.6 (CH_ar), 131.5 (CH_ar),

133.3 (C_ar), 134.1 (C_ar), 138.1 (C_ar), 139.5 (C_ar), 140.9 (C_ar), 153.1

(C_ar), 169.2 (OCOMe) ppm. C₂₈H₂₆O₄S (428.28): calcd. C 73.34,

H 5.71, S 6.99; found C 73.29, H 5.77, S 6.89.

(–)-[aS,1R,(S)R]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfinyl)-

ethyl]phenyl}naphthalene (aS-17): White gum; R_f= 0.17 (EtOAc/

(–)-[aS,1R,(S)R]-1-{2-[1-Methoxy-2-(p-tolylsulfinyl)ethyl]phenyl}-2-

methylnaphthalene (aS-29): White solid (99% yield; dr Ͼ 99:1); R_f

= 0.28 (Et₂O). M.p. = 123–126 °C. [α]²_D⁰= –27.4 (c = 1, CHCl₃).

hexanes, 2:1). [α]²_D⁰= –8.6 (c = 1, CHCl ). IR (neat): ν = 2927,

˜

3

1621, 1594, 1509, 1464, 1332, 1255, 1266, 1176, 1111, 1067, 1021,

975, 921, 869, 811, 763. H NMR (CDCl₃, 300 MHz): δ = 2.31 (s, ¹H NMR (CDCl₃, 300 MHz): δ = 2.02 (s, 3 H, CH₃), 2.35 (s, 3 H,

3 H, CH₃), 2.76–2.85 [X part of an ABX system (m), 1 H, CH₂], CH₃), 2.47 (X part of an ABX system, J_A,X= 12.4, J_B,X= 1.9 Hz,

2.87 [s, 3 H, CH(OCH₃)], 3.44–3.53 [AB part of an ABX system 1 H, CH₂), 3.06 (s, 3 H, OCH₃), 3.39 [AB part of an ABX system,

(m), 2 H, CH(OMe) + CH₂], 3.72 (s, 3 H, OCH₃), 7.03 (A₂B₂, J_A,BJ_A,B= 11.1, J_A,X= 12.3, J_B,X= 1.9 Hz, ∆ν = 36 Hz, CH₂, 2 H,

1

= 7.9 Hz, ∆ν = 57 Hz, 4 H, H_ar), 7.03 (br. d, J = 8.4 Hz, 1 H, H_ar),

CH(OMe)], 6.78 (A₂B₂, J_A,B= 8.2 Hz, ∆ν = 44 Hz, 4 H, H_ar), 6.96

7.08 (dd, J = 7.4, 1.4 Hz, 1 H, H_ar), 7.17 (d, J = 9 Hz, 1 H, H_ar), (br. d, J = 8.3 Hz, 1 H, H_ar), 7.07 (dd, J = 7.5, 1.4 Hz, 1 H, H_ar),

7.21 (ddd, J = 8.4, 6.8, 1.5 Hz, 1 H, H_ar), 7.3 (ddd, J = 8.1, 6.8, 7.22 (d, J = 8.3 Hz, 1 H, H_ar), 7.3 (ddd, J = 8.3, 6.9, 1.3 Hz, 1 H,

1.3 Hz, 1 H, H_ar), 7.39 (td, J = 7.4, 1.4 Hz, 1 H, H_ar), 7.5 (td, J =

H_ar), 7.4 (td, J = 7.3, 1.4 Hz, 1 H, H_ar), 7.45 (ddd, 1 H, J = 8.1,

7.4, 1.4 Hz, 1 H, H_ar), 7.66 (dd, J = 7.6, 1.4 Hz, 1 H, H_ar), 7.78 6.9, 1 Hz, H_ar), 7.51 (td, J = 7.5, 1.4 Hz, 1 H, H_ar), 7.68 (dd, J =

(d, J = 8.1 Hz, 1 H, H_ar), 7.83 (d, J = 9 Hz, 1 H, H_ar) ppm. ¹³C

NMR (CDCl₃, 75 MHz): δ = 21.4 (CH₃), 56.0 [CH(OCH₃)], 56.2

(OCH₃), 64.3 (CH₂), 75.9 [CH(OMe)], 112.8 (CH_ar), 121.6 (C_ar),

7.3, 1.3 Hz, 1 H, H_ar), 7.71 (d, J = 8.3 Hz, 1 H, H_ar), 7.86 (d, J =

8.1 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 20.2

(CH₃), 21.3 (CH₃), 56.3 (OCH₃), 64.5 (CH₂), 76.1 [CH(OMe)],

123.4 (CH_ar), 123.9 (CH_ar), 124.3 (CH_ar), 125.7 (CH_ar), 126.3 123.6 (CH_ar), 125.0 (CH_ar), 125.5 (CH_ar), 125.8 (CH_ar), 126.3

(CH_ar), 127.8 (CH_ar), 128.0 (CH_ar), 128.4 (CH_ar), 128.6 (C_ar), 129.2 (CH_ar), 127.4 (CH_ar), 127.9 (CH_ar), 127.9 (CH_ar), 128.2 (CH_ar),

(CH_ar), 129.4 (CH_ar), 131.2 (CH_ar), 132.7 (C_ar), 135.4 (C_ar), 138.2 128.4 (CH_ar), 129.4 (CH_ar), 130.5 (CH_ar), 131.8 (C_ar), 132.2 (C_ar),

(C_ar), 139.3 (C_ar), 141.1 (C_ar), 153.8 (C_ar) ppm.

132.6 (C_ar), 134.6 (C_ar), 137.7 (C_ar), 138.2 (C_ar), 138.9 (C_ar), 140.8

Eur. J. Org. Chem. 2005, 1113–1128

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1123

P.-E. Broutin, F. Colobert

(C_ar) ppm. C₂₇H₂₆O₂S (414.56): calcd. C 78.23, H 6.32, S 7.73; H, OMe), 3.6 [AB part of an ABX system, J_A,B= 13.1, J_A,X= 2.9,

FULL PAPER

found C 78.13, H 6.37, S 7.62.

J_B,X= 10.9 Hz, ∆ν = 150 Hz, 2 H, CH(OMe), CH₂], 6.76 (br. d, J

= 8.3 Hz, 1 H, H_ar), 6.76 (dd, J = 7.5, 1.8 Hz, 1 H, H_ar), 6.85 (td,

J = 7.5, 1 Hz, 1 H, H_ar), 7.19 (br. d, J_A,B= 7.5 Hz, ∆ν = 63 Hz, 1

H, H_ar), 7.22 (A₂B₂, J = 7.8 Hz, 4 H, H_ar), 7.27 (ddd, J = 8.3, 7.5,

1.8 Hz, 1 H, H_ar), 7.32 (td, 1 H, J = 7.5 Hz, H_ar), 7.39 (br. d, J =

7.5 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 20.1

(CH₃), 21.5 (CH₃), 55.0 (OMe), 56.0 (OMe), 65.0 (CH₂), 75.8

(CH), 110.8 (CH_ar), 120.54 (CH_ar), 123.02 (CH_ar), 124.24 (CH_ar),

127.09 (C_ar), 128.04 (CH_ar), 128.63 (CH_ar), 129.2 (CH_ar), 129.7

(CH_ar), 129.8 (CH_ar), 137.0 (C_ar), 137.1 (C_ar), 137.5 (C_ar), 139.9

(C_ar), 141.2 (C_ar), 156.4 (C_ar) ppm. C₂₄H₂₆O₃S (394.53): calcd. C

73.06, H 6.64, S 8.13; found C 72.9, H 6.75, S 7.95.

[1R,(S)R]-1-{2-[1-Methoxy-2-(p-tolylsulfinyl)ethyl]-6-methyl-

phenyl}naphthalene (30): Orange solid (88% yield; dr 90:10); R_f=

0.24 (Et₂O). C₂₇H₂₆O₂S: calcd. C 78.23, H 6.32, S 7.73; found C

78.11, H 6.46, S 7.67.

[aS,1R,(S)R]-30:¹H NMR (CDCl₃, 300 MHz): δ = 1.81 (s, 3 H,

CH₃), 2.36 (s, 3 H, CH₃), 2.4 (X part of an ABX system, J_A,X

=

12.3, J_B,X= 1.9 Hz, 1 H, CH₂), 3.03 (s, 3 H, OMe), 3.47 [AB part

of an ABX system, J_A,B= 11.3, J_A,X= 12.3, J_B,X= 1.9 Hz, ∆ν =

34 Hz, 2 H, CH₂, CH(OMe)], 6.79 (A₂B₂, J_A,B= 8.3 Hz, ∆ν =

21 Hz, 4 H, H_ar), 6.99 (dd, J = 6.8, 1 Hz, 1 H, H_ar), 7.08 (d, J =

8.3 Hz, 1 H, H_ar), 7.26 (br. d, J = 6.8 Hz, 1 H, H_ar), 7.35 (dd, J =

8.3, 6.8 Hz, 1 H, H_ar), 7.36 (ddd, J = 8.0, 6.8, 1.3 Hz, 1 H, H_ar), (–)-[aR,1R,(S)R]-2Ј-Methoxy-6-[1-methoxy-2-(p-tolylsulfinyl)ethyl]-

7.42 (t, J = 7.5 Hz, 1 H, H_ar), 7.51 (br. d, J = 7.5 Hz, 1 H, H_ar), 2-methylbiphenyl (aR-32): Yellow solid (19% yield). R_f= 0.25

7.53 (ddd, J = 8.0, 6.8, 1 Hz, 1 H, H_ar), 7.57 (br. d, J = 8.3 Hz, 1

(Et₂O). M.p. 133–135 °C. [α]²_D⁰= –19.4 (c = 0.5, CHCl₃). IR (neat):

H, H_ar), 7.92 (br. d, J = 8 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, ν = 2929, 1594, 1581, 1500, 1459, 1301, 1263, 1242, 1108, 1042,

˜

75 MHz): δ = 19.9 (CH₃), 21.4 (CH_3ar), 30.2 (OMe), 56.0 (CH₂),

1023, 1010, 976, 813, 772. ¹H NMR (CDCl₃, 300 MHz): δ = 1.9 (s,

64.8 (CH), 75.6 (CH_ar), 123.4 (CH_ar), 123.7 (CH_ar), 125.0 (CH_ar), 3 H, CH₃), 2.42 (s, 3 H, CH₃), 2.62 (X part of an ABX system,

125.1 (CH_ar), 125.7 (CH_ar), 125.8 (CH_ar), 126.0 (CH_ar), 126.1 J_A,X= 2.8, J_B,X= 12.4 Hz, 1 H, CH₂), 3 (s, 3 H, OMe), 3.48 [AB

(CH_ar), 126.5 (CH_ar), 127.4 (CH_ar), 128.3 (CH_ar), 129.5 (C_ar), 131.8 part of an ABX system, J_A,B= 10.9, J_A,X= 2.8, J_B,X= 12.4 Hz,

(C_ar), 133.5 (C_ar), 136.2 (C_ar), 137.2 (C_ar), 137.5 (C_ar), 138.8 (C_ar), ∆ν = 42 Hz, 2 H, CH(OMe), CH₂], 3.52 (s, 3 H, OMe), 6.73 (br.

140.8 (C_ar) ppm.

d, 1 H, J = 8.2, 0.9 Hz, H_ar), 6.79 (dd, J = 7.4, 1.7 Hz, 1 H, H_ar),

6.92 (td, J = 7.4, 1.1 Hz, 1 H, H_ar), 7.19 (A₂B₂, J_A,B= 7.9 Hz, ∆ν

[aR,1R,(S)R]-30:¹H NMR (CDCl₃, 300 MHz): δ = 1.83 (s, 3 H,

CH₃), 2.29 (s, 3 H, CH₃), 2.4 [A part of an ABX system (m), 1 H, = 36 Hz, 4 H, H_ar), 7.19 (br. d, J = 7.3 Hz, 1 H, H_ar), 7.3 (ddd, J

CH₂], 2.72 (B part of an ABX system, J = 12.8 Hz, 1 H, CH₂), = 8.2, 7.4, 1.7 Hz, 1 H, H_ar), 7.31 (t, J = 7.3 Hz, 1 H, H_ar), 7.39

2.85 (s, 3 H, OMe), 3.23 [X part of an ABX system, J_A,X= 10.8,

J_B,X= 3 Hz, 1 H, CH(OMe)], 6.75–7.92 (m, 14 H, H_ar) ppm.

(br. d, J = 7.3 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ

= 20.26 (CH₃), 21.51 (CH₃), 54.82 (OMe), 56.12 (OMe), 64.37

(CH₂), 76.45 (CH), 110.48 (CH_ar), 121.01 (CH_ar), 122.7 (CH_ar),

124.63 (CH_ar), 126.85 (C_ar), 128.01 (CH_ar), 128.83 (CH_ar), 129.47

(CH_ar), 129.74 (CH_ar), 131.09 (CH_ar), 136.9 (C_ar), 137.16 (C_ar),

137.52 (C_ar), 139.52 (C_ar), 141.17 (C_ar), 155.15 (C_ar) ppm.

[1R,(S)R]-6-[1-Methoxy-2-(p-tolylsulfinyl)ethyl]-2,2Ј-dimethylbiphe-

nteyl (31): Orange gum (82% yield; dr: 75:25); R_f= 0.27 (Et₂O).

C₂₄H₂₆O₂S: calcd. C 76.15, H 6.92, S 8.47; found C 75.79, H 6.88,

S 8.23.

[aS,1R,(S)R]-31:¹H NMR (CDCl₃, 300 MHz): δ = 1.18 (s, 3 H, [1R,(S)R]-1-{2-Methoxy-6-[1-methoxy-2-(p-tolylsulfinyl)ethyl]-

CH₃), 1.86 (s, 3 H, CH₃), 2.41 (s, 3 H, CH₃), 2.52 (X part of an

ABX system, 1 H, CH₂), 2.99 (s, 3 H, OMe), 3.57 [AB part of an

ABX system, J_A,B= 10.9, J_A,X= 2.69, J_B,X= 12.5 Hz, ∆ν = 66 Hz,

phenyl}naphthalene (33): White solid (86.1% yield; dr 95:5); R_f=

0.28 (Et₂O). C₂₇H₂₆O₃S: calcd. C 75.32, H 6.09, S 7.45; found C

74.84, H 6.12, S 7.54.

2 H, CH(OMe), CH₂], 6.73 (br. d, J = 7.5 Hz, 1 H, H_ar), 7.04 (br. [aR,1R,(S)R]-33:¹H NMR (CDCl₃, 300 MHz): δ = 2.36 (s, 3 H,

t, J = 7.5 Hz, 1 H, H_ar), 7.09 (br. t, J = 7.5 Hz, 1 H, H_ar), 7.18 (m, CH₃), 2.37 (X part of an ABX system, 1 H, CH₂), 3.04 (s, 3 H,

1 H, H_ar), 7.19 (A₂B₂, J_A,B= 8.3 Hz, ∆ν = 51 Hz, 4 H, H_ar), 7.19 OMe), 3.46 [AB part of an ABX system, J_A,B= 11, J_A,X= 2.3,

(m, 1 H, H_ar), 7.31 (t, J = 7.7 Hz, 1 H, H_ar), 7.4 (d, J = 7.7 Hz, 1

J_B,X= 12.5 Hz, ∆ν = 55 Hz, 2 H, CH(OMe), CH₂], 3.57 (s, 3 H,

H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 19.3 (CH₃Ј), 19.9 OMe), 6.78 (A₂B₂, J_A,B= 8.3 Hz, ∆ν = 28 Hz, 4 H, H), 6.95 (d, J

(CH₃), 21.5 (CH₃), 56.0 (OMe), 64.5 (CH₂), 75.2 (CH), 123.5

(CH_ar), 124.2 (CH), 125.7 (C_ar), 127.1 (CH_ar), 128.0 (CH_ar), 128.4

= 8.3 Hz, 1 H, H_ar), 7.01 (dd, J = 7, 1.3 Hz, 1 H, H_ar), 7.11 (d, J

= 8.3 Hz, 1 H, H_ar), 7.27 (dd, J = 7.8, 1 Hz, 1 H, H_ar), 7.33 (dd, J

(CH_ar), 129.5 (CH_ar), 129.7 (CH_ar), 129.8 (CH_ar), 130.3 (CH_ar), = 8.3, 7 Hz, 1 H, H_ar), 7.34 (ddd, J = 8.3, 6.8, 1.3 Hz, 1 H, H_ar),

135.7 (C_ar), 136.3 (C_ar), 136.4 (C_ar), 137.7 (C_ar), 140.3 (C_ar), 141.5 7.49 (t, J = 8.3 Hz, 1 H, H_ar), 7.52 (m, 1 H, H_ar), 7.76 (br. d, J =

(C_ar) ppm.

8.3 Hz, 1 H, H_ar), 7.9 (br. d, J = 8 Hz, 1 H, H_ar) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ = 21.5 (CH₃), 55.8 (OMe), 56.2 (OMe), 64.5

[aR,1R,(S)R]-31:¹H NMR (CDCl₃, 300 MHz): δ = 1.8 (s, 3 H,

CH₃), 1.84 (s, 3 H, CH₃), 2.39 (s, 3 H, CH₃), 2.75 (m, 1 H, CH₂), (CH₂), 75.4 (CH), 110.3 (CH_ar), 118.1 (CH_ar), 123.8 (CH_ar), 125.0

3 (s, 3 H, OMe), 3.4 [m, 2 H, CH(OMe), CH₂], 6.72–7.41 (m, 11 (CH_ar), 125.3 (CH_ar), 126.0 (CH_ar), 126.3 (CH_ar), 126.4 (CH_ar),

H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 19.2 (CH₃), 20.0 127.6 (CH_ar), 128.3 (CH_ar), 128.5 (C_ar), 129.5 (CH_ar), 129.6 (CH_ar),

(CH₃), 21.4 (CH₃), 56.3 (OMe), 64.5 (CH₂), 76.5 (CH), 122.9

(CH_ar), 124.5 (CH), 124.4 (C_ar), 126.2 (CH_ar), 127.4 (CH_ar), 127.9

132.5 (C_ar), 133.5 (C_ar), 133.6 (C_ar), 138.9 (C_ar), 139.3 (C_ar), 141.0

(C_ar), 157.4 (C_ar) ppm.

(CH_ar), 129.4 (CH_ar), 129.5 (CH_ar), 129.9 (CH_ar), 134.5 (CH_ar), [aS,1R,(S)R]-33:¹H NMR (CDCl₃, 300 MHz): δ = 2.3 (s, 3 H,

136.5 (C_ar), 136.6 (C_ar), 139.3 (C_ar), 139.5 (C_ar), 139.8 (C_ar), 141.3 CH₃), 2.7 (AB part of an ABX system, J_A,B= 12.5, J_A,X= 3.1,

(C_ar) ppm.

J_B,X= 10 Hz, ∆ν = 115 Hz, 2 H, CH₂), 2.84 (s, 3 H, OMe), 3.25

(X part of an ABX system, J_A,X= 3.1, J_B,X= 10 Hz, 1 H, CH),

3.59 (s, 3 H, OMe), 6.50–7.90 (m, 14 H, H_ar) ppm.

(+)-[aS,1R,(S)R]-2Ј-Methoxy-6-[1-methoxy-2-(p-tolylsulfinyl)ethyl]-

2-methylbiphenyl (aS-32): Yellow solid (70% yield). R_f= 0.18

(Et₂O). M.p. 148–150 °C. [α]²_D⁰= +1.8 (c = 0.6, CHCl₃). IR (neat):

[2R,(S)R]-2-Methoxy-6-[1-methoxy-2-(p-tolylsulfinyl)ethyl]-2Ј-meth-

ylbiphenyl (34): Light-yellow solid (86% yield; dr 90:10); R_f= 0.41

ν = 2919, 1596, 1496, 1465, 1436, 1295, 1265, 1243, 1228, 1187,

˜

1

1101, 1040, 1027, 799, 782. H NMR (CDCl₃, 300 MHz): δ = 1.9 (Et₂O/CH₂Cl₂, 2:1).

(s, 3 H, CH₃), 2.41 (s, 3 H, CH₃), 2.71 (X part of an ABX system, [aR,1R,(S)R]-34: ¹H NMR (CDCl₃, 300 MHz): δ = 1.87 (s, 3 H,

J_A,X= 2.9, J_B,X= 10.9 Hz, 1 H, CH₂), 3 (s, 3 H, OMe), 3.59 (s, 3

CH₃), 2.44 (s, 3 H, CH₃), 2.98 (AB part of an ABX system, J_A,B

1124

www.eurjoc.org

Eur. J. Org. Chem. 2005, 1113–1128

Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

= 12.6, J_A,X= 10.9, J_B,X= 2.8 Hz, ∆ν = 293 Hz, 2 H, CH₂), 3.09

(s, 3 H, OMe), 3.68 (s, 3 H, OMe), 3.75 (X part of an ABX system,

J_A,X= 10.9, J_B,X= 2.8 Hz, 1 H, CH), 6.76 (d, J = 7.5 Hz, 1 H,

7.22 (ddd, J = 8.3, 6.8, 1.2 Hz, 1 H, H_ar), 7.27 (ddd, J = 8.3, 6.8,

1.2 Hz, 1 H, H_ar), 7.42 (dd, J = 8.3, 7 Hz, 1 H, H_ar), 7.46 (ddd, J

= 8.3, 6.8, 1.2 Hz, 1 H, H_ar), 7.53 (ddd, J = 8.3, 6.8, 1.2 Hz, 1 H,

H_ar), 6.89 (d, J = 7.9 Hz, 1 H, H_ar), 7.04 (t, J = 7.5 Hz, 1 H, H_ar), H_ar), 7.78 (d, J = 8.7 Hz, 1 H, H_ar), 7.86 (d, J = 8.3 Hz, 1 H, H_ar),

7.14 (m, 1 H, H_ar), 7.2 (A₂B₂, J = 8.1 Hz, 4 H, H_ar), 7.2 (m, 1 H, 7.91 (d, J = 8.3 Hz, 1 H, H_ar), 7.96 (d, J = 8.3 Hz, 1 H, H_ar), 8.03

H_ar), 7.21 (m, 1 H, H_ar), 7.41 (t, J_A,B= 8.1 Hz, ∆ν = 36 Hz, 1 H,

(d, J = 8.7 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ =

21.5 (CH₃), 56.1 (OMe), 64.2 (CH₂), 75.8 (CH), 123.0 (CH_ar), 123.8

H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 19.4 (CH₃), 21.4

(CH₃), 55.5 (OMe), 56.1 (OMe), 64.2 (CH₂), 75.9 (CH), 109.9 (CH_ar), 125.0 (CH_ar), 125.7 (CH_ar), 126.1 (CH_ar), 126.2 (CH_ar),

(CH_ar), 117.8 (CH_ar), 124.3 (CH_ar), 125.3 (CH_ar), 127.2 (CH_ar), 126.4 (CH_ar), 126.6 (CH_ar), 126.7 (CH_ar), 126.9 (CH_ar), 127.8

128.9 (CH_ar), 129.1 (CH_ar), 129.5 (C_ar), 129.8 (CH_ar), 129.8 (CH_ar), (CH_ar), 127.9 (CH_ar), 128.3 (CH_ar), 129.1 (CH_ar), 129.4 (CH_ar),

134.7 (C_ar), 136.8 (C_ar), 138 (C_ar), 139.3 (C_ar), 141.4 (C_ar), 156.5

132.7 (C_ar), 132.9 (C_ar), 133.0 (C_ar), 133.5 (C_ar), 134.5 (C_ar), 135.0

(C_ar), 136.7 (C_ar), 138.8 (C_ar), 141.0 (C_ar) ppm.

(C_ar) ppm. [aS,1R,(S)R]-34:¹H NMR (CDCl₃, 300 MHz): δ = 1.88

(s, 3 H, CH₃), 2.42 (s, 3 H, CH₃), 2.81 (m, 1 H, CH₂), 2.99 (s, 3 H, [aS,1R,(S)R]-36:¹H NMR (CDCl₃, 300 MHz): δ = 2.33 (s, 3 H,

OMe), 3.44–3.49 [m, 2 H, CH₂, CH(OMe)], 3.68 (s, 3 H, OMe), CH₃), 2.78 (X part of an ABX system, J_A,X= 12.6, J_B,X= 3 Hz, 1

6.76–7.44 (m, 11 H, H_ar) ppm.

H, CH₂), 3.04 (s, 3 H, OMe), 3.46 (B part of an ABX system, J =

10.9, 12.6, 3 Hz, 1 H, CH₂), 3.58–3.64 [A part of an ABX system

(m), 1 H, CH(OMe)], 6.81–8.82 (m, 17 H, H_ar) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ = 30.3 (CH₃), 56.5 (OMe), 64.4 (CH₂), 76.3

(CH), 122.7 (CH_ar), 124.1 (CH_ar), 125.3 (CH_ar), 125.4 (CH_ar), 125.4

(CH_ar), 125.9 (CH_ar), 126 (CH_ar), 126.4 (CH_ar), 127.7 (CH_ar), 127.8

(CH_ar), 128 (CH_ar), 128.1 (CH_ar), 128.4 (CH_ar), 129.1 (CH_ar), 129.5

(CH_ar), 131.7 (C_ar), 133.1 (C_ar), 133.1 (C_ar), 133.5 (C_ar), 134.6 (C_ar),

134.9 (C_ar), 136.3 (C_ar), 138.9 (C_ar), 141.2 (C_ar) ppm.

(–)-[aS,1R,(S)R]-2,2Ј-Dimethoxy-6-[1-methoxy-2-(p-tolylsulfinyl-

ethyl]biphenyl (aS-35): White solid (70% yield). R_f= 0.23 (Et₂O).

M.p. 118–120 °C. [α]²_D⁰= –74.7 (c = 1.1, CHCl ). IR (neat): ν =

˜

3

2941, 2922, 1594, 1581, 1466, 1436, 1293, 1266, 1231, 1250, 1231,

1106, 1070, 1043, 1030, 986, 910, 806, 758, 750. ¹H NMR (CDCl₃,

300 MHz): δ = 2.43 (s, 3 H, CH₃), 2.59 (AB part of an ABX system,

J_A,B= 12.6, J_A,X= 10.9, J_B,X= 2.8 Hz, ∆ν = 246 Hz, 2 H, CH₂),

3.04 (s, 3 H, OMe), 3.5 (s, 3 H, OMe_arЈ), 3.58 (X part of an ABX

system, J_A,X= 10.9, J_B,X= 2.8 Hz, 1 H, CH), 3.66 (s, 3 H, OMe_ar),

6.71 (dd, J = 8.3, 0.9 Hz, 1 H, H_ar), 6.85 (dd, J = 7.2, 1.8 Hz, 1

H, H_ar), 6.89 (dd, J = 8.1, 0.9 Hz, 1 H, H_ar), 6.93 (td, J = 7.2, 1.1

Hz, 1 H, H_ar), 7.17 (dd, J = 8, 0.8 Hz, 1 H, H_ar), 7.19 (A₂B₂, J_A,B

= 7.9 Hz, ∆ν = 31 Hz, 4 H, H_ar), 7.3 (ddd, J = 8.3, 7.2, 1.8 Hz, 1

H, H_ar), 7.38 (t, J = 8 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 21.5 (CH₃), 54.9 (OMe), 55.8 (OMe), 56.2 (OMe),

64.1 (CH₂), 76.2 (CH), 110.5 (CH_ar), 110.6 (CH_ar), 117.3 (CH_ar),

120.8 (CH_ar), 123.8 (C_ar), 124.6 (CH_ar), 126.4 (C_ar), 128.8 (CH_ar),

129.1 (CH_ar), 129.8 (CH_ar), 132 (CH_ar), 139.2 (C_ar), 139.5 (C_ar),

141.2 (C_ar), 155.4 (C_ar), 157 (C_ar) ppm. C₂₄H₂₆O₄S (394.53): calcd.

C 70.22, H 6.38, S 7.81; found C 70.11, H 6.5, S 7.46.

[1R,(S)R]-2-[1-Methoxy-2-(p-tolylsulfinyl)ethyl]-1-(o-tolyl)naphtha-

lene (37): Orange solid (75% yield; dr 75:25); R_f= 0.29 (Et₂O).

[aS,1R,(S)R]-37:¹H NMR (CDCl₃, 300 MHz): δ = 1.7 (s, 3 H,

CH₃), 2.44 (s, 3 H, CH₃), 2.59 (X part of an ABX system, J_A,X

=

2.6, J_B,X= 12.6 Hz, 1 H, CH₂), 3.04 (s, 3 H, OMe), 3.77 [AB part

of an ABX system, J_A,B= 11, J_A,X= 2.6, J_B,X= 12.6 Hz, ∆ν =

71 Hz, 2 H, CH(OMe), CH₂], 6.87 (dd, J = 7.3, 1.3 Hz, 1 H, H_ar),

7.1 (m, 1 H, H_ar), 7.13 (m, 1 H, H_ar), 7.14 (m, 1 H, H_ar), 7.24

(A₂B₂, J_A,B= 8.2 Hz, ∆ν = 45 Hz, 4 H, H_ar), 7.29 (m, 1 H, H_ar),

7.34 (m, 1 H, H_ar), 7.46 (ddd, J = 8.2, 6.9, 1.3 Hz, 1 H, H_ar), 7.68

(d, J = 8.7 Hz, 1 H, H_ar), 7.86 (d, J = 8.1 Hz, 1 H, H_ar), 7.93 (d,

J = 8.7 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 19.6

(Me), 21.5 (CH₃), 56.1 (OMe), 64.2 (CH₂), 75.3 (CH), 123.1 (H_ar),

124.3 (CH_ar), 125.7 (H_ar), 126.2 (H_ar), 126.2 (H_ar), 126.4 (H_ar),

127.5 (H_ar), 128.0 (H_ar), 128.7 (H_ar), 129.4 (H_ar), 129.7 (CH_ar),

129.8 (H_ar), 130.3 (C_ar), 132.0 (C_ar), 133.1 (C_ar), 133.3 (C_ar), 136.4

(C_ar), 136.9 (C_ar), 138.1 (C_ar), 141.6 (C_ar) ppm.

(+)-[aR,1R,(S)R]-2,2Ј-Dimethoxy-6-[1-methoxy-2-(p-tolylsulfinyl)-

ethyl]biphenyl (aR-35): Light-yellow solid (10% yield). R_f= 0.13

(Et₂O). M.p. 134–137 °C. [α]²_D⁰= +35.5 (c = 1, CHCl₃). IR (neat):

ν = 2921, 1596, 1582, 1496, 1466, 1438, 1292, 1254, 1102, 1068,

˜

1037, 1027, 986, 910, 808, 801, 758, 738. ¹H NMR (CDCl₃,

300 MHz): δ = 2.41 (s, 3 H, CH₃), 2.98 (s, 3 H, OMe), 3.04 (AB

part of an ABX system, J_A,B= 13, J_A,X= 10.9, J_B,X= 2.8 Hz, ∆ν

= 219 Hz, 2 H, CH₂), 3.58 (s, 3 H, OMe), 3.66 (s, 3 H, OMe_ar),

3.77 (X part of an ABX system, J_A,X= 10.9, J_B,X= 2.8 Hz, 1 H,

CH), 6.74 (br. d, J = 8.3 Hz, 1 H, H_ar), 6.81 (dd, J = 7.3, 2.3 Hz,

1 H, H_ar), 6.85 (td, J = 7.3, 0.9 Hz, 1 H, H_ar), 6.89 (dd, J = 8.3,

0.9 Hz, 1 H, H_ar), 7.17 (dd, J = 8.3, 0.9 Hz, 1 H, H_ar), 7.23 (A₂B₂,

J_A,B= 7.7 Hz, ∆ν = 48 Hz, 1 H, H_ar), 7.26 (td, J = 7.3, 2.3 Hz, 1

H, H_ar), 7.39 (t, J = 8.3 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 21.47 (CH_3ar(pTol)), 55.2 (OMe), 55.9 (OMe), 56.0

(OMe), 64.2 (CH₂), 75.4 (CH), 110.3 (CH_ar), 110.9 (CH_ar), 117.8

(CH_ar), 120.3 (CH_ar), 124.3 (CH_ar[pTol)), 124.3 (C_ar), 127.2 (C_ar),

128.7 (CH_ar), 129.1 (CH_ar), 129.7 (CH_ar), 130.5 (CH_ar), 138.7 (C_ar),

139.9 (C_ar), 141.3 (C_ar), 157.0 (C_ar), 157.0 (C_ar) ppm.

[aS,1R,(S)R]-37:¹H NMR (CDCl₃, 300 MHz): δ = 1.78 (s, 3 H,

CH₃), 2.41 (s, 3 H, CH₃), 2.82 (X part of an ABX system, J_A,X

=

2.6, J_B,X= 10.8 Hz, 1 H, CH₂), 3.02 (s, 3 H, OMe), 3.63 (AB part

of an ABX system, J = 10.8, 2.6, 10.8 Hz, 2 H, CH(OMe), CH₂),

6.83–7.95 (m, 14 H, H_ar) ppm.

(+)-[aS,1R,(S)R]-1-(2-Methoxyphenyl)-2-[1-methoxy-2-(p-tolylsulfi-

nyl)ethyl]naphthalene (aS-38): White solid (60% yield). R_f= 0.2

(Et₂O). M.p. 131–133 °C. [α]²_D⁰= +28.4 (c = 1, CHCl₃). IR (neat):

ν = 2922, 1597, 1492, 1448, 1431, 1248, 1231, 1103, 1084, 1044,

˜

1028, 992, 965, 835, 812, 780, 762, 752. ¹H NMR (CDCl₃,

300 MHz): δ = 2.43 (s, 3 H, CH₃), 2.99 (s, 3 H, OMe), 3.22 (AB

part of an ABX system, J_A,B= 12.8, J_A,X= 11.1, J_B,X= 2.8 Hz,

∆ν = 244 Hz, 2 H, CH₂), 3.52 (s, 3 H, OMe), 3.95 (X part of an

ABX system, J_A,X= 11.1, J_B,X= 2.8 Hz, 1 H, CH), 6.8 (d, J =

8.5 Hz, 1 H, H_ar), 6.9 (dd, J = 7.4, 2.2 Hz, 1 H, H_ar), 6.94 (td, J =

7.4, 1 Hz, 1 H, H_ar), 7.2 (br. d, J = 6.8 Hz, 1 H, H_ar), 7.27 (A₂B₂,

[1R,(S)R]-2-[1-Methoxy-2-(p-tolylsulfinyl)ethyl]-1,1Ј-binaph-

thalenyl (36): White solid (88% yield; dr 85:15); R_f= 0.25 (Et₂O/ J_A,B= 7.9 Hz, ∆ν = 58 Hz, 4 H, H_ar), 7.31 (ddd, J = 8.1, 6.8, 1.3

EtOAc, 4:1). Hz, 1 H, H_ar), 7.33 (m, 1 H, H_ar), 7.45 (ddd, J = 8.1, 6.8, 1.2 Hz,

[aS,1R,(S)R]-36:¹H NMR (CDCl₃, 300 MHz): δ = 2.38 (s, 3 H, 1 H, H_ar), 7.67 (d, J = 8.7 Hz, 1 H, H_ar), 7.85 (br. d, J = 8.1 Hz, 1

CH₃), 2.49 [X part of an ABX system (m), 1 H, CH₂], 3.04 (s, 3

H, OMe), 3.58–3.68 [AB part of an ABX system (m), 2 H,

CH(OMe), CH₂], 6.83 (s, 4 H, H_ar), 6.94 (d, J = 8.3 Hz, 1 H, H_ar),

H, H_ar), 7.93 (d, J = 8.7 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 21.5 (CH₃), 55.1 (OMe), 55.9 (OMe), 64.1 (CH₂),

75.8 (CH), 110.9 (CH_ar), 120.4 (CH_ar), 123.0 (CH_ar), 124.3 (CH_ar),

7.01 (d, J = 8.3 Hz, 1 H, H_ar), 7.12 (dd, J = 7, 1.1 Hz, 1 H, H_ar), 125.8 (C_ar), 126.0 (CH_ar), 126.1 (CH_ar), 126.3 (CH_ar), 127.9 (CH_ar),

Eur. J. Org. Chem. 2005, 1113–1128

P.-E. Broutin, F. Colobert

FULL PAPER

128.7 (CH_ar), 129 (CH_ar), 129.7 (CH_ar), 130.8 (CH_ar), 132.6 (C_ar), (CH_ar), 124.8 (CH_ar), 125.7 (CH_ar), 127.1 (CH_ar), 128.1 (CH_ar),

133.1 (C_ar), 133.9 (C_ar), 135.3 (C_ar), 139.9 (C_ar), 141.4 (C_ar), 157.3 128.3 (CH_ar), 128.6 (CH_ar), 129.6 (CH_ar), 131.9 (C_ar), 132.0 (C_ar),

(C_ar) ppm.

132.0 (C_ar), 132.1 (CH_ar), 132.6 (C_ar), 139.1 (C_ar), 140.8 (C_ar), 141.2

(C_ar), 145.3 (C_ar), 148.5 (C_ar) ppm. C₂₇H₂₅NO₄S (459.56): calcd. C

70.57, H 5.48, N 3.05, S 6.98; found C 70.49, H 5.61, N 3.22, S

6.98.

[aR,1R,(S)R]-1-(2-Methoxyphenyl)-2-[1-methoxy-2-(p-tolylsulfinyl)-

ethyl]naphthalene (aR-38): Yellow solid (15% yield). R_f= 0.3

(Et₂O). M.p. 162–165 °C. [α]²_D⁰= –28.1 (c = 0.21, CHCl₃). IR (neat):

(+)-[aR,1S]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfonyl)ethyl]-4-

nitrophenyl}naphthalene (aR-42). Major Atropodiastereomer: Brown

solid (70% yield). R_f= 0.25 (EtOAc/hexanes, 1:1). M.p. 159–162 °C.

ν = 2922, 1597, 1492, 1448, 1431, 1248, 1231, 1103, 1084, 1044,

˜

1028, 992, 965, 835, 812, 780, 762, 752. ¹H NMR (CDCl₃,

300 MHz): δ = 2.44 (s, 3 H, CH₃), 2.67 (X part of an ABX system,

J_A,X= 3.2, J_B,X= 12.6 Hz, 1 H, CH₂), 3.03 (s, 3 H, OMe), 3.48 (s,

[α]²_D⁰= +4.5 (c = 1, CHCl ). IR (neat): ν = 1594, 1510, 1462, 1301,

˜

3

1311, 1255, 1247, 1134, 1112, 1084, 1062, 818, 811, 168, 743. ¹H

NMR (CDCl₃, 300 MHz): δ = 2.36 (s, 3 H, CH₃), 2.77 (s, 3 H,

CH[OCH₃)), 3.46 (AB part of an ABX system, J_A,B= 14.7, J_A,X

= 9.7, J_B,X= 2.2 Hz, ∆ν = 29 Hz, 2 H, CH₂), 3.89 (s, 3 H, OCH₃),

4.21 [X part of an ABX system, J_A,X= 9.7, J_B,X= 2.2 Hz, 1 H,

CH(OMe)], 7.13–7.21 (m, 2 H, H_ar), 7.27 (ddd, J = 8.2, 6.7, 1.5

Hz, 1 H, H_ar), 7.34 (ddd, J = 8.1, 6.7, 1.5 Hz, 1 H, H_ar), 7.35 (A₂B₂,

J_A,B= 8.3 Hz, ∆ν = 107 Hz, 4 H, H_ar), 7.41 (d, J = 8.9 Hz, 1 H,

H_ar), 7.42 (td, J = 7.3, 1.8 Hz, 1 H, H_ar), 7.47 (td, J = 7.3, 1.5 Hz,

1 H, H_ar), 7.55 (m, J = 8.1 Hz, 1.5 Hz, 1 H, H_ar), 7.86 (dd, 1 H, J

= 8.9 Hz, H_ar), 7.98 (d, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 21.5 (CH₃), 55.9 [CH(OCH₃)], 56.2 (OCH₃), 63.0

(CH₂), 75.3 [CH(OMe)], 112.8 (CH_ar), 121.3 (C_ar), 123.4 (CH_ar),

124.3 (CH_ar), 125.6 (CH_ar), 126.4 (CH_ar), 127.9 (CH_ar), 128.0

(CH_ar), 128.1 (CH_ar), 128.3 (CH_ar), 128.9 (C_ar), 129.2 (CH_ar), 130.0

(CH_ar), 131.3 (CH_ar), 133.1 (C_ar), 135.4 (C_ar), 137.2 (C_ar), 138.5

(C_ar), 143.8 (C_ar), 153.9 (C_ar) ppm. C₂₇H₂₆O₄S (446.56): calcd. C

72.62, H 5.87, S 7.18; found C 72.81, H 5.94, S 7.21.

3 H, OMe), 3.66 [AB part of an ABX system, J_A,B= 10.9, J_A,X

=

3.2, J_B,X= 12.6 Hz, ∆ν = 67 Hz, 2 H, CH₂, CH(OMe)], 6.81 (d, J

= 8.5 Hz, 1 H, H_ar), 6.89 (dd, J = 7.3, 1.9 Hz, 1 H, H_ar), 6.98 (td,

J = 7.5, 1.1 Hz, 1 H, H_ar), 7.22 (br. d, J = 8.5 Hz, 1 H, H_ar), 7.23

(A₂B₂, J_A,B= 8.5 Hz, ∆ν = 43 Hz, 4 H, H_ar), 7.3 (ddd, J = 8.3, 6.8,

1.5 Hz, 1 H, H_ar), 7.39 (ddd, J = 8.3, 7.5, 1.9 Hz, 1 H, H_ar), 7.44

(ddd, J = 8.1, 6.8, 1.3 Hz, 1 H, H_ar), 7.68 (d, J = 8.7 Hz, 1 H, H_ar),

7.85 (br. d, J = 8.3 Hz, 1 H, H_ar), 7.92 (d, J = 8.7 Hz, 1 H, H_ar)

ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.5 (CH₃), 54.9 (OMe),

56.2 (OMe), 64.1 (CH₂), 76.5 (CH), 110.6 (CH_ar), 120.9 (CH_ar),

122.5 (CH_ar), 124.6 (CH), 125.5 (C_ar), 125.9 (CH_ar), 126.0 (CH_ar),

126.1 (CH_ar), 127.9 (CH_ar), 128.6 (CH_ar), 129.2 (CH_ar), 129.8

(CH_ar), 132.1 (CH_ar), 132.7 (C_ar), 133.2 (C_ar), 134.5 (C_ar), 134.8

(C_ar), 139.5 (C_ar), 141.3 (C_ar), 155.8 (C_ar) ppm.

(–)-[aR,1R,(S)R]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfinyl)eth-

yl]-4-nitrophenyl}naphthalene (aR-39): Light-yellow solid (93%

yield). R_f= 0.13 (Et₂O). M.p. 72–75 °C. [α]²_D⁰= –80.3 (c = 1,

CHCl ). IR (neat): ν = 1740, 1730, 1604, 1522, 1455, 1435, 1344,

˜

3

(–)-[aS,1R]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfonyl)ethyl]-4-

nitrophenyl}naphthalene (aS-42). Minor Atropodiastereomer: Brown

gum (12% yield). R_f= 0.13 (EtOAc/hexanes, 1:1). [α]²_D⁰= –64.4 (c

1304, 1248, 1125, 1086, 1031, 897, 811, 738. ¹H NMR (CDCl₃,

300 MHz): δ = 2.39 (s, 3 H, CH₃), 2.79 (AB part of an ABX system,

J_A,B= 12.9, J_A,X= 11, J_B,X= 2.4 Hz, ∆ν = 296 Hz, 2 H, CH₂),

3.15 (s, 3 H, OMe), 3.67 (s, 3 H, OMe), 3.73 (X part of an ABX

= 0.22, CHCl ). IR (neat): ν = 2925, 2849, 1621, 1594, 1508, 1448,

˜

3

1

1315, 1301, 1256, 1137, 1085, 1067, 1020, 986, 810, 746. H NMR

system, J_A,X= 11, J_B,X= 2.4 Hz, 1 H, CH), 6.85 (A₂B₂, J_A,B

=

(CDCl₃, 300 MHz): δ = 2.04 (s, 3 H, CH₃), 2.38 [s, 3 H,

CH(OCH₃)], 3.97 (AB part of an ABX system, J_A,B= 14.4, J_A,X

= 10.7, J_B,X= 1.6 Hz, ∆ν = 168 Hz, 2 H, CH₂), 3.23 (s, 3 H,

OCH₃), 4.37 [X part of an ABX system, J_A,X= 10.7, J_B,X= 1.6 Hz,

1 H, CH(OMe)], 7.13–7.99 (m, 14 H, H_ar) ppm. ¹³C NMR (CDCl₃,

75 MHz): δ = 21.55 (CH₃), 55.87 [CH(OCH₃)], 56.78 (OCH₃),

62.48 (CH₂), 74.95 [CH(OMe)], 112.71 (CH_ar), 121.32 (C_ar), 123.62

(CH_ar), 123.97 (CH_ar), 125.48 (CH_ar), 127 (CH_ar), 127.47 (CH_ar),

128.09 (CH_ar), 128.29 (CH_ar), 128.32 (CH_ar), 129.1 (C_ar), 129.26

(CH_ar), 129.89 (CH_ar), 131.36 (CH_ar), 133.54 (C_ar), 135.09 (C_ar),

136.65 (C_ar), 138.84 (C_ar), 143.57 (C_ar), 152.78 (C_ar) ppm.

8.1 Hz, ∆ν = 35 Hz, 4 H, H_ar), 6.95 (br. d, J = 8.7 Hz, 1 H, H_ar),

7.12 (d, J = 9 Hz, 1 H, H_ar), 7.27 (d, J = 8.7 Hz, 1 H, H_ar), 7.35

(ddd, J = 8.3, 6.9, 1.4 Hz, 1 H, H_ar), 7.43 (ddd, J = 8.3, 6.9, 1.5

Hz, 1 H, H_ar), 7.88 (d, J = 8.3 Hz, 1 H, H_ar), 7.9 (d, J = 9 Hz, 1

H, H_ar), 8.24 (dd, J = 8.3, 2.5 Hz, 1 H, H_ar), 8.54 (d, J = 2.5 Hz,

1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 50 MHz): δ = 21.5 (CH₃), 55.6

[CH(OCH₃)], 56.8 (OCH₃), 63.9 (CH₂), 75.9 (CH), 111.9 (CH_ar),

119.2 (C_ar), 121.0 (CH_ar), 123.0 (CH_ar), 123.5 (CH_ar), 123.9 (CH_ar),

124.2 (CH_ar), 127.7 (CH_ar), 128.3 (CH_ar), 128.9 (C_ar), 129.6 (CH_ar),

130.5 (CH_ar), 132.7 (C_ar), 132.7 (CH_ar), 139.3 (C_ar), 141.2 (C_ar),

141.7 (C_ar), 142.4 (C_ar), 148.4 (C_ar), 152.0 (C_ar) ppm. C₂₇H₂₅NO₅S

(475.56): calcd. C 68.19, H 5.3, N 2.95, S 6.74; found C 67.87, H

5.53, N 3, S 6.47.

(+)-[aR,1S,(S)R]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfinyl)eth-

yl]phenyl}naphthalene (aR-45). Major Atropodiastereomer: White

solid (49% yield). R_f= 0.3 (EtOAc/hexanes, 1:1). M.p. 155–158 °C.

(–)-[aS,1R,(S)R]-1-{2-[1-Methoxy-2-(p-tolylsulfinyl)ethyl]-4-nitro-

phenyl}-2-methylnaphthalene (aS-40): Light-orange solid (84%

yield). R_f= 0.23 (Et₂O). M.p. 187–189 °C. [α]²_D⁰= –16 (c = 1,

[α]²_D⁰= +214.4 (c = 1.2, CHCl ). IR (neat): ν = 2923, 1622, 1594,

˜

3

1510, 1461, 1356, 1333, 1257, 1105, 1067, 1031, 1016, 801, 764,

1

745. H NMR (CDCl₃, 300 MHz): δ = 2.38 (s, 3 H, CH₃), 3 [s, 3

CHCl ). IR (neat): ν = 2948, 1596, 1510, 1342, 1213, 1097, 1083,

H, CH(OCH₃)], 3.01 (AB part of an ABX system, J_A,B= 13.3, J_A,X

˜

3

1043, 979, 912, 916, 747. ¹H NMR (CDCl₃, 300 MHz): δ = 2.02 (s, = 10.7, J_B,X= 2.1 Hz, ∆ν = 50 Hz, 2 H, CH₂), 3.85 (s, 3 H, OCH₃),

3 H, CH₃), 2.37 (s, 3 H, CH₃), 2.83 (AB part of an ABX system,

J_A,B= 12.8, J_A,X= 10.7, J_B,X= 2.5 Hz, ∆ν = 259 Hz, 2 H, CH₂),

3.13 (s, 3 H, OMe), 3.58 [X part of an ABX system, J_A,X= 10.7,

J_B,X= 2.5 Hz, 1 H, CH(OMe)], 6.82 (A₂B₂, J_A,B= 8.2 Hz, ∆ν =

4.42 [X part of an ABX system, J_A,X= 10.7, J_B,X= 2.1 Hz, 1 H,

CH(OMe), CH₂], 7.18–7.51 (m, 11 H, H_ar), 7.62 (dd, J = 7.6, 1.4

Hz, 1 H, H_ar), 7.85 (dd, J = 8.2, 2.2 Hz, 1 H, H_ar), 7.97 (d, J =

8.9 Hz, 1 H, H_ar) ppm. ¹³C NMR (CDCl₃, 75 MHz): δ = 21.3

52 Hz, 4 H, H_ar), 6.88 (br. d, J = 8.3 Hz, 1 H, H_ar), 7.25 (d, J = (CH₃), 55.8 [CH(OCH₃)], 56.6 (OCH₃), 66.3 (CH₂), 74 [CH(OMe)],

8.3 Hz, 1 H, H_ar), 7.3 (d, J = 8.3 Hz, 1 H, H_ar), 7.36 (ddd, J = 8.2, 121.7 (CH_ar), 121.3 (C_ar), 123.4 (CH_ar), 123.7 (CH_ar), 124.5 (CH_ar),

6.9, 1.3 Hz, 1 H, H_ar), 7.5 (ddd, J = 8.2, 6.9, 1.3 Hz, 1 H, H_ar), 125.9 (CH_ar), 126.4 (CH_ar), 128 (CH_ar), 128.1 (CH_ar), 128.2 (CH_ar),

7.78 (d, J = 8.4 Hz, 1 H, H_ar), 7.9 (d, J = 8 Hz, 1 H, H_ar), 8.27 (d,

J = 8.3 Hz, 1 H, 2.5 Hz, H_ar), 8.58 (dd, 1 H, J = 2.5 Hz, H_ar) ppm.

¹³C NMR (CDCl₃, 75 MHz): δ = 20.2 (CH₃), 21.5 (CH₃), 57.0

(OCH₃), 64.0 (CH₂), 75.9 (CH), 121.5 (CH_ar), 123.2 (CH_ar), 123.7

129 (C_ar), 129.7 (CH_ar), 130 (CH_ar), 131.3 (CH_ar), 133.4 (C_ar), 135.9

(C_ar), 139.1 (C_ar), 140.9 (C_ar), 142.1 (C_ar), 154 (C_ar) ppm.

C₂₇H₂₆O₃S (430.56): calcd. C 75.32, H 6.09, S 7.45; found C 75.09,

H 6.35, S 7.37.

1126

www.eurjoc.org

Eur. J. Org. Chem. 2005, 1113–1128

Asymmetric Biaryl Suzuki Cross-Coupling Reaction

FULL PAPER

[3] S. P. Stanforth, Tetrahedron 1998, 54, 263–303.

[4] L. Pu, Chem. Rev. 1998, 98, 2405–2494.

(+)-[aS,1S,(S)R]-2-Methoxy-1-{2-[1-methoxy-2-(p-tolylsulfinyl)eth-

yl]phenyl}naphthalene (aS-45). Minor Atropodiastereomer: White

solid (40% yield). R_f= 0.1 (EtOAc/hexanes, 1:1). M.p. 41–43 °C.

[5] a) A. I. Meyers, K. A. Lutomski, J. Am. Chem. Soc. 1982, 104,

879–881; b) A. I. Meyers, R. J. Himmelsbach, J. Am. Chem.

Soc. 1985, 107, 682–685; c) J. M. Wilson, D. Cram, J. Org.

Chem. 1984, 49, 4930–4943; d) J. M. Wilson, D. J. Cram, J. Am.

Chem. Soc.1982, 104, 881–884; e) B. H. Lipshutz, J. M. Keith,

Angew. Chem. Int. Ed. 1999, 38, 3530–3533; f) K. S. Feldmann,

R. S. Smith, J. Org. Chem. 1996, 61, 2606–2612; g) S. Saito, T.

Kano, H. Muto, M. Nakadai, H. Yamamoto, J. Am. Chem.

Soc. 1999, 121, 8943–8944; h) G-G. Lin, M. Zhong, Tetrahe-

dron: Asymmetry 1997, 8, 1369–1372; i) K. Kamikawa, M. Ue-

mura, Synlett 2000, 938–949; j) J. Brusse, J. L. G. Groenendijk,

J. M. te Copele, A. C. A. Jansen, Tetrahedron 1985, 41, 3313–

3319; k) T. Hayashi, K. Hayashizaki, T. Kiyoi, Y. Ito, J. Am.

Chem. Soc. 1988, 10, 8153–8156; l) T. Hayashi, K. Hayashizaki,

Y. Ito, Tetrahedron Lett. 1989, 30, 215–218; m) T. Hayashi, S.

Niizuma, T. Kamikawa, N. Suzuki, Y. Uozumi, J. Am. Chem.

Soc. 1995, 117, 9101–9102; n) T. Kamikawa, T. Hayashi, Tetra-

hedron 1999, 55, 3455–3466.

[6] F. Diederich, P. J. Stang, in Metal-Catalyzed Cross Coupling

Reactions, Wiley-VCH, Weinheim, 1998, pp. 49–97.

[7] K. C. Nicolaou, H. Li, C. N. C. Boddy, J. M. Ramanjulu, T.-Y.

Yue, S. Natarajan, X.-J. Chu, S. Bräse, F. Rübsam, Chem. Eur.

J. 1999, 5, 2584–2601.

[8] a) A. N. Cammidge, K. V. L. Crepy, Chem. Commun. 2000,

1723–1724; b) , A. N. Cammidge, K. V. L. Crepy, Tetrahedron

2004, 60, 4377–4386.

[α]²_D⁰= +257.8 (c = 1.9, CHCl ). IR (neat): ν = 2934, 1620, 1593,

˜

3

1508, 1463, 1380, 1333, 1265, 1253, 1105, 1086, 1047, 1017, 806,

760, 749. ¹H NMR (CDCl₃, 300 MHz): δ = 2.32 (s, 3 H, CH₃),

2.49 (AB part of an ABX system, J_A,B= 13.3, J_A,X= 10.7, J_B,X

2.4 Hz, ∆ν = 61 Hz, 2 H, CH₂), 2.37 [s, 3 H, CH(OCH₃)], 2.88 (s,

3 H, OCH₃), 4.56 [X part of an ABX system, J_A,X= 10.7, J_B,X

=

2.4 Hz, 1 H, CH(OCH₃)], 6.93 (A₂B₂, J_A,B= 8.1 Hz, ∆ν = 69 Hz,

4 H, H_ar), 7.01–7.04 (m, 1 H, H_ar), 7.19–7.25 (m, 2 H, H_ar), 7.32–

7.50 (m, 4 H, H_ar), 6.68 (dd, J = 7.6, 1.6 Hz, 1 H, H_ar), 7.92 (d, J

= 8.2 Hz, 1 H, H_ar), 8 (d, J = 8.9 Hz, 1 H, H_ar) ppm. ¹³C NMR

(CDCl₃, 75 MHz): δ = 21.3 (CH₃), 55.9 [CH(OCH₃)], 57 (OCH₃),

64.6 (CH₂), 74.2 [CH(OMe)], 112.9 (CH_ar), 121.4 (C_ar), 123.3

(CH_ar), 123.9 (CH_ar), 124.3 (CH_ar), 125.5 (CH_ar), 126.5 (CH_ar),

127.8 (CH_ar), 128.1 (CH_ar), 128.4 (CH_ar), 129.2 (C_ar), 129.5 (CH_ar),

130 (CH_ar), 131.4 (CH_ar), 133.8 (C_ar), 135.4 (C_ar), 139.4 (C_ar), 141

(C_ar), 141.7 (C_ar), 153 (C_ar) ppm.

X-ray Analysis of (–)-[aS,1R,(S)R]-(11): C₂₆H₂₄O₃S,

415.54 g mol^–1, orthorhombic, space group

P2₁2₁2₁,

11.1954(3) Å, 11.6368(3) Å, 16.6489(4) Å, V

M

a

=

b

=

c

=

2169.00(9) Å³, Z = 4, colorless crystal 0.12 × 0.08 × 0.06 mm³,

D_calcd.= 1.27 g cm^–3, F₀₀₀= 876, µ(Mo-K_α) = 0.174 cm^–1, θ_max

=

173 K. A total of 6311 reflections were collected. The final cycle of

the full-matrix least-squares refinement was based on 3256 ob-

served reflections [I Ͼ 3σ(I)] and 275 variable parameters and con-

verged with unweighted and weighted agreement factors of R =

0.046 and R_w= 0.059, respectively (GOF = 1.025). The maximum

peak in the final difference Fourier map corresponded to

0.678 e Å^–3.

[9] J. Yin, S. L. Buchwald, J. Am. Chem. Soc. 2000, 122, 12 051–

12 052.

[10] A. Herrbach, A. Marinetti, O. Baudoin, D. Guenard, F. Guer-

itte, J. Org. Chem. 2003, 12, 4897–4905.

[11] J. F. Jensen, M. Johannsen, Org. Lett. 2003, 5, 3025–3028.

[12] K. Mikami, T. Miyamoto, M. Hatano, Chem. Commun. 2004,

2082–2083.

X-ray Analysis of (+)-[aS,1R,(S)R]-(38): C₂₇H₂₆O₃S,

M

=

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The diastereomeric ratio was established by H NMR studies:

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www.eurjoc.org

1127

P.-E. Broutin, F. Colobert

FULL PAPER

[29] The diastereomeric ratio was established by H NMR studies:

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1

[33] We oxidized 17 using the same experimental procedure as for

the synthesis of 41 starting from 12 (see Experimental Section).

[34] Reduction of 17 and 45 was performed in MeOH using Raney

Ni at room temperature.

[35] We thank Dr. Nathalie Gruber for assistance with the

analysis of the crystal structure (Service commun Rayons X,

4

rue Blaise Pascal, 67070 Strasbourg cedex, E-mail:

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sercomrx@chimie.u-strasbg.fr).

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Delft, The Netherlands, 1997.

Received September 9, 2004

1128

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An asymmetric biaryl Suzuki cross-coupling reaction: Stereogenic benzylic carbinols as chiral auxiliaries

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