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.

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

References and Notes

<A NAME="RS00910ST-1">1</A> Mitzel TM. Palomo C. Jendza K. J. Org. Chem.  2002,  67:  136 

<A NAME="RS00910ST-2">2</A> Frimpong K. Wzorek J. Lawlor C. Spencer K. Mitzel T. J. Org. Chem.  2009,  74:  5861 

<A NAME="RS00910ST-3">3</A> Pelc MJ. Zakarian A. Tetrahedron Lett.  2006,  47:  7519 

<A NAME="RS00910ST-4">4</A> Armstrong A. Challinor L. Moir JH. Angew. Chem. Int. Ed.  2007,  46:  5369 

<A NAME="RS00910ST-5">5</A> Ma M. Peng L. Li C. Zhang X. Wang J. J. Am. Chem. Soc.  2005,  127:  15016 

<A NAME="RS00910ST-6A">6a</A> Wee AGH. Shi Q. Wang Z. Hatton K. Tetrahedron: Asymmetry  2003,  14:  897 

<A NAME="RS00910ST-6B">6b</A> Bach T. Korber CJ. J. Org. Chem.  2000,  65:  2358 

<A NAME="RS00910ST-7A">7a</A> Inoue M. Miyazaki K. Uehara H. Maruyama M. Hirama M. Proc. Natl. Sci. U.S.A.  2004,  101:  12013 

<A NAME="RS00910ST-7B">7b</A> For a review, see: Dilworth BM. McKervey MA. Tetrahedron  1986,  42:  3731 

<A NAME="RS00910ST-8A">8a</A> Normant H. Castro CR. C. R. Hebd. Seances Acad. Sci.  1964,  259:  830 

<A NAME="RS00910ST-8B">8b</A> Gross H. Hoft E. Angew. Chem., Int. Ed. Engl.  1967,  6:  335 

<A NAME="RS00910ST-8C">8c</A> Ogura K. Fujitha M. Takahashi K. Iida H. Chem. Lett.  1982,  11:  1697 

<A NAME="RS00910ST-8D">8d</A> Cohen T. Matz JR. J. Am. Chem. Soc.  1985,  106:  6902 

<A NAME="RS00910ST-8E">8e</A> Nakatsuka S. Takai K. Utimoto K. J. Org. Chem.  1986,  51:  5045 

<A NAME="RS00910ST-9">9</A> Chu DTH. J. Org. Chem.  1983,  48:  3571 

<A NAME="RS00910ST-10A">10a</A> Paterson I. Fleming I. Tetrahedron Lett.  1979,  993 

<A NAME="RS00910ST-10B">10b</A> Paterson I. Tetrahedron  1988,  44:  4207 

<A NAME="RS00910ST-10C">10c</A> Reetz MT. Huttenhain S. Walz P. Lowe U. Tetrahedron Lett.  1979,  4971 

<A NAME="RS00910ST-10D">10d</A> Groth U. Huhn T. Richter N. Liebigs Ann. Chem.  1993,  49 

<A NAME="RS00910ST-11A">11a</A> Bohme H. Ber. Dtsch. Chem. Ges.  1936,  69:  1610 

<A NAME="RS00910ST-11B">11b</A> Vedejs E. Mullins MJ. Renga JM. Singer SP. Tetrahedron Lett.  1978,  519 

<A NAME="RS00910ST-11C">11c</A> Arai K. Iwamura H. Oki M. Bull. Chem. Soc. Jpn.  1975,  48:  3319 

<A NAME="RS00910ST-12">12</A> Bordwell FG. Pitt BM. J. Am. Chem. Soc.  1955,  77:  572 

<A NAME="RS00910ST-13">13</A> 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

<A NAME="RS00910ST-14">14</A> 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 

<A NAME="RS00910ST-15">15</A>

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.

<A NAME="RS00910ST-16">16</A> (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 

<A NAME="RS00910ST-17">17</A>

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.

<A NAME="RS00910ST-18">18</A>

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

<A NAME="RS00910ST-19">19</A>

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.

<A NAME="RS00910ST-20A">20a</A> Trost BM. Belletire JL. Godleski S. McDougal PG. Balkovec JM. J. Org. Chem.  1986,  51:  2370 

<A NAME="RS00910ST-20B">20b</A> Trost BM. Bunt RC. Pulley SR. J. Org. Chem.  1994,  59:  4202 

<A NAME="RS00910ST-21A">21a</A> Miller EG. Rayner DR. Mislow K. J. Am. Chem. Soc.  1966,  88:  3139 

<A NAME="RS00910ST-21B">21b</A> Braverman S. Stabinsky Y. Chem. Commun.  1967,  270 

<A NAME="RS00910ST-21C">21c</A> Evans DA. Andrews GC. Acc. Chem. Res.  1974,  7:  147 

<A NAME="RS00910ST-22">22</A> Armstrong A. Emmerson DPG. Org. Lett.  2009,  11:  1547 

<A NAME="RS00910ST-23A">23a</A> McLaughlin JL. J. Nat. Prod.  2008,  71:  1311 

<A NAME="RS00910ST-23B">23b</A> Davoren JE. Harcken C. Martin SF. J. Org. Chem.  2008,  73:  391 

<A NAME="RS00910ST-24">24</A> Petranek J. Vecera M. Collect. Czech. Chem. Commun.  1959,  24:  2191 

<A NAME="RS00910ST-25A">25a</A> Kirmse W. Kapps M. Chem. Ber.  1968,  101:  994 

<A NAME="RS00910ST-25B">25b</A> Doyle MP. Griffin JH. Chinn MS. van Leusen D. J. Org. Chem.  1984,  49:  1917 

<A NAME="RS00910ST-26">26</A> Calo V. Nacci A. Fiandanese V. Volpe A. Tetrahedron Lett.  1997,  38:  3289