Highly Stereoselective Preparation of Chiral α-Substituted Sulfides from α-Chloro Sulfides via 1,2-Asymmetric Induction

Abstract

A C-S stereogenic center is created with efficient stereo­control by 1,2-asymmetric induction due to a vicinal C-O stereogenic center. Propargylic, allylic, and alkyl sulfides are readily prepared in good yield and stereoselectivity from α-chloro sulfides. The allylic sulfide have been converted to the corresponding sulfoxide/sulfilimine/sulfur ylide and subjected to [2,3]-sigmatropic rearrangement. The efficient 1,3-chirality transfer observed in this reaction eventually results in a net 1,4-chirality transfer.

Key words

α-chloro sulfide - rearrangement - sulfoxide - stereo­selective synthesis - asymmetric induction

References and Notes

• 1 Mitzel TM. Palomo C. Jendza K. J. Org. Chem.  2002,  67:  136 
• 2 Frimpong K. Wzorek J. Lawlor C. Spencer K. Mitzel T. J. Org. Chem.  2009,  74:  5861 
• 3 Pelc MJ. Zakarian A. Tetrahedron Lett.  2006,  47:  7519 
• 4 Armstrong A. Challinor L. Moir JH. Angew. Chem. Int. Ed.  2007,  46:  5369 
• 5 Ma M. Peng L. Li C. Zhang X. Wang J. J. Am. Chem. Soc.  2005,  127:  15016 
• 6a Wee AGH. Shi Q. Wang Z. Hatton K. Tetrahedron: Asymmetry  2003,  14:  897 
• 6b Bach T. Korber CJ. J. Org. Chem.  2000,  65:  2358 
• 7a Inoue M. Miyazaki K. Uehara H. Maruyama M. Hirama M. Proc. Natl. Sci. U.S.A.  2004,  101:  12013 
• 7b For a review, see: Dilworth BM. McKervey MA. Tetrahedron  1986,  42:  3731 
• 8a Normant H. Castro CR. C. R. Hebd. Seances Acad. Sci.  1964,  259:  830 
• 8b Gross H. Hoft E. Angew. Chem., Int. Ed. Engl.  1967,  6:  335 
• 8c Ogura K. Fujitha M. Takahashi K. Iida H. Chem. Lett.  1982,  11:  1697 
• 8d Cohen T. Matz JR. J. Am. Chem. Soc.  1985,  106:  6902 
• 8e Nakatsuka S. Takai K. Utimoto K. J. Org. Chem.  1986,  51:  5045 
• 9 Chu DTH. J. Org. Chem.  1983,  48:  3571 
• 10a Paterson I. Fleming I. Tetrahedron Lett.  1979,  993 
• 10b Paterson I. Tetrahedron  1988,  44:  4207 
• 10c Reetz MT. Huttenhain S. Walz P. Lowe U. Tetrahedron Lett.  1979,  4971 
• 10d Groth U. Huhn T. Richter N. Liebigs Ann. Chem.  1993,  49 
• 11a Bohme H. Ber. Dtsch. Chem. Ges.  1936,  69:  1610 
• 11b Vedejs E. Mullins MJ. Renga JM. Singer SP. Tetrahedron Lett.  1978,  519 
• 11c Arai K. Iwamura H. Oki M. Bull. Chem. Soc. Jpn.  1975,  48:  3319 
• 12 Bordwell FG. Pitt BM. J. Am. Chem. Soc.  1955,  77:  572 
• 13 For the preparation of the acetate corresponding to sulfide 6, see: Taniguchi N. J. Org. Chem.  2006,  71:  7874 ; the resulting acetate was hydrolyzed and the hydroxy group protected as its silyl ether
• 14 Anhydrous zinc bromide was prepared as a 1.5 M solution in dry THF by heating at reflux for 2 h a 1.5 M solution of DCE containing excess acid washed zinc, see: Brown DS. Charreau P. Hansson T. Ley SV. Tetrahedron  1991,  47:  1311 
• 16 (Z)-1-Octenylmagnesium bromide was prepared from (Z)-1-bromo octene and Mg turnings while (E)-1-octenyl­­-magnesium chloride was prepared from (E)-1-iodo octene by halogen-metal exchange, see: Ren H. Krasovskiy A. Knochel P. Org. Lett.  2004,  6:  4215 
• 20a Trost BM. Belletire JL. Godleski S. McDougal PG. Balkovec JM. J. Org. Chem.  1986,  51:  2370 
• 20b Trost BM. Bunt RC. Pulley SR. J. Org. Chem.  1994,  59:  4202 
• 21a Miller EG. Rayner DR. Mislow K. J. Am. Chem. Soc.  1966,  88:  3139 
• 21b Braverman S. Stabinsky Y. Chem. Commun.  1967,  270 
• 21c Evans DA. Andrews GC. Acc. Chem. Res.  1974,  7:  147 
• 22 Armstrong A. Emmerson DPG. Org. Lett.  2009,  11:  1547 
• 23a McLaughlin JL. J. Nat. Prod.  2008,  71:  1311 
• 23b Davoren JE. Harcken C. Martin SF. J. Org. Chem.  2008,  73:  391 
• 24 Petranek J. Vecera M. Collect. Czech. Chem. Commun.  1959,  24:  2191 
• 25a Kirmse W. Kapps M. Chem. Ber.  1968,  101:  994 
• 25b Doyle MP. Griffin JH. Chinn MS. van Leusen D. J. Org. Chem.  1984,  49:  1917 
• 26 Calo V. Nacci A. Fiandanese V. Volpe A. Tetrahedron Lett.  1997,  38:  3289 

15

The reaction of chloro sulfide 7 with 1-octynylmagnesium chloride proceeded to afford the product in lower yield (50%), while reaction with 1-lithio octyne did not yield any desired product.

17

General Experimental Procedure
To a solution of 1-octyne (165 mg, 1.5 mmol) in dry THF (0.8 mL) cooled at -10 ˚C was added i-PrMgCl˙LiCl (1 mL, 1.5 mmol, 1.5 M in THF) and stirred for 30 min at the same temperature. To the so generated Grignard reagent, ZnBr₂ (1.1 mL, 1.65 mmol, 1.5 M in THF) was added at 0 ˚C and stirred for 30 min. To the organozinc reagent maintained at 0 ˚C was added a solution of chloro sulfide (0.5 mmol) in benzene (5 mL), the reaction mixture stirred gradually allowing it to attain r.t., and stirred further for a period of 7 h when TLC examination indicated complete consumption of the chloro sulfide. The reaction mixture was cooled to 0 ˚C and quenched by the addition of an aq sat. NH₄Cl solution. It was allowed to warm to r.t. and diluted with
Et₂O (5 mL), the layers were separated and aqueous layer extracted with Et₂O (3 × 10 mL). The combined organic layers were washed with H₂O (5 mL), brine (5 mL), dried over Na₂SO₄, and the solvent evaporated under reduced pressure to afford a crude compound which was purified by column chromatography using hexanes as the eluent to afford the pure product 9a (192 mg, 0.43 mmol) in 86% yield as a liquid. TLC: R _f = 0.34 (hexanes). IR (KBr): 3445, 3063, 2954, 2928, 1586, 1463, 1384, 1253, 1094, 827, 837, 777, 695 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.60-7.30 (m, 10 H), 4.91 (d, J = 6.8 Hz, 1 H), 4.16 (td, J = 2.3, 6.8 Hz, 1 H), 2.16 (dt, J = 2.3, 6.8 Hz, 2 H), 1.50-1.15 (m, 8 H), 1.00-0.90 (m, 12 H), 0.20 (s, 3 H), 0.0 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 142.00, 135.62, 132.11, 128.58, 127.82, 127.69, 127.36, 126.89, 87.32, 77.45, 48.91, 31.45, 28.51, 28.47, 25.89, 22.62, 18.35, 14.20, -4.55, -4.83. ESI-MS: m/z 469 [M + NH₄]⁺. ESI-HRMS: m/z calcd for C₂₈H₄₀ONaSiS: 475.2467; found: 475.2466.

18

Substrate 13 was prepared by deprotection of acetonide moiety in 10 followed by protection of the resulting diol, see Supporting Information.

19

The signals for the olefinic, methine protons of the acetonide and CH ₂OBn appear downfield in ester 18 compared to the corresponding protons of ester 19, see Supporting Information.