摘要:

I O S Aryl O O Aryl OH 6–10 1–5 i I O OH S Ph O O 11 12 (49% l u = 7 1) i R1 R3 O R2 R1 O S R2 15 • S Ph O O O R3 O S R2 R1 R3 13 O O • 14 • O Stereoselective radical aryl migrations from sulfur to carbon Armido Studer*† and Martin Bossart Laboratorium für Organische Chemie Eidgenössische Technische Hochschule ETH-Zentrum Universitätstrasse 16 CH-8092 Zürich Switzerland Stereoselective radical 1,5 aryl migrations from sulfur (in arenesulfonates) to carbon with diastereoselectivities of up to 14:1 are presented. C(sp2)–C(sp3) bonds occur in many natural products and new methods for their stereoselective formation are important. In the literature there are only a very few methods for stereoselective C(sp3)–aryl bond formation. The Heck1 and Michael2 reactions have to be mentioned at this point.Numerous examples of radical aryl transfers (C?C,3 N?C,4 O?C5 and S?C6) have been published however we were surprised to find only three reports of stereoselective radical aryl migrations.7 Herein we describe highly diastereoselective 1,5 aryl migrations from sulfur to carbon. Motherwell in his pioneering studies has shown that intramolecular ipso substitution in arenesulfonates by aryl radicals is an efficient method for biaryl synthesis.6 Based on our work on the stereoselective phenyl migration from Si to C8 we decided to test arenesulfonates as possible ‘arene sources’ in the intramolecular stereoselective radical ipso substitution reaction. To this end arenesulfonates 1–5 were prepared in moderate to good yields (50–90%) from (like)-4-iodopentan- 2-ol and the corresponding commercially available sulfonyl chlorides in pyridine.9 The racemic‡ iodo alcohol was easily prepared from (meso)-pentan-2,4-diol according to established procedures.10 We were pleased to find that ipso substitution occurs smoothly (Scheme 1 Table 1).Slow addition of tin hydride to 1 in refluxing benzene under optimized conditions§ afforded the known11 alcohol 6 in 76% yield with high selectivity (u:l = 13:1 entry 1). Both electron poor and electron rich arenes can be stereoselectively transferred. Thus the p-fluorophenyl derivative 7 was obtained in 59% yield with a slightly lower selectivity (10:1 entry 2).¶ In the case of the electron rich anisyl and dansyl derivatives a lower yield was observed (8 50% 9:1; 10 52% 11:1 entries 3 and 5). Even heteroarenes can be used in the ipso substitution as shown for the thienyl transfer (9 74% 9:1 entry 4).As a side product the corresponding reduced (dehalogenated) sulfonate was always observed in these aryl migration reactions. In order to study the 1,2-stereoinduction sulfonate 11 was prepared as a 1:1 mixture of diastereoisomers. Aryl migration under analoguous conditions provided alcohol 12 in 49% yield (l:u = 7:1 Scheme 2). The relative configuration of the major isomer was assigned after oxidation (Swern) to the corresponding known12 aldehyde. From the stereochemical outcome of the reactions discussed above we suggest the following model to explain the observed selectivities radical 13 undergoes intramolecular ipso attack at the aryl group of the sulfonate to form cyclohexadienyl radical 14. Products derived from 1,7 addition were not observed.We assume that the low energy transition state for the formation of 14 resembles a chair with the substituents in equatorial positions. Fragmentation (re-aromatization) then affords radical 15 which after SO2 extrusion and reduction leads to the corresponding alcohol. It is not clear how fast the SO2 extrusion process is by which the corresponding alkoxyl radical is formed. However in the crude product mixture of the aryl migration reactions we never observed sulfur-containing products derived from 15; therefore we assume that the SO2 extrusion is faster than trapping of the intermediate radical 15 with Bu3SnH.· According to this model the observed 1,3- (?unlike products) and 1,2-selectivity (? like product) can be readily understood. As a first application of this method we studied a one pot reaction sequence where a radical addition reaction is followed by a stereoselective phenyl migration.Sulfonate 16 was prepared from the corresponding homoallylic alcohol and benzenesulfonyl chloride as described above (43%).9 Radical acceptor 16 and ethyl iodoacetate (1.5 equiv.) were reacted under atom transfer conditions13 in benzene [Bu3SnSnBu3 (10%) hn 300 W sun lamp 0.1 M] to afford iodide 17 which after dilution (? 0.05 M) was directly transformed upon slow addition of Bu3SnH (1.8 equiv. over 7 h) and AIBN (0.25 Scheme 1 Reagents and conditions i Bu3SnH AIBN syringe pump benzene (0.03 M) Table 1 Stereoselective aryl transfer from sulfur to carbon Entry Sulfonate Aryl Product Yield (%) Ratio (u:l)a 1 1 Ph 6 76 13:1 2 2 4-FC6H4 7 59 10:1 3 3 4-MeOC6H4 8 50 9:1 4 4 thienyl 9 74 9:1 5 5 5-Me2N-naphthyl 10 52 11:1b a Determined by GC analysis.b Determined by 1H NMR spectroscopy. Scheme 2 Reagents and conditions i Bu3SnH AIBN syringe pump benzene (0.05 M) Chem. Commun. 1998 2127 CO2Et O I CO2Et OH Ph O S Ph O O S Ph O O i 16 17 18 (24% u l = 14 1) ii equiv.) to 18 (Scheme 3). Hydroxy ester 18 was isolated in 24% yield (unoptimized) as a 14:1 (u:l) mixture of diastereoisomers. The intermediate iodide 17 was formed with no selectivity as shown in a separate experiment by 1H NMR analysis of a sample taken after the iodine transfer reaction. In summary we have shown that the intramolecular ipso substitution is an efficient method for the stereoselective C(sp2)–C(sp3) bond formation. Since many sulfonyl chlorides are commercially available a variety of aryl groups can be stereoselectively transferred to form products which are difficult to prepare by any other method.We are grateful to Professor Dr D. Seebach for generous financial support and to Professor Dr D. P. Curran for helpful discussions. Notes and References † E-mail studer@org.chem.ethz.ch ‡ All the compounds described herein were prepared as racemic mixtures. In the schemes only one enantiomer is shown. § General procedure Bu3SnH (1.5 equiv.) and AIBN (0.3 equiv.) in benzene (0.8–1.2 M) were added over 7 h (syringe pump) to a refluxing solution of the iodide in benzene (0.03 M). After complete addition the reaction mixture was stirred under reflux for additional 30 min. The mixture was then allowed to cool to room temperature and MeLi (5 equiv.) was slowly added.After stirring for 30 min the reaction mixture was hydrolyzed with saturated aq. NH4Cl. Extraction with Et2O and washing of the organic phase with brine afforded after drying (MgSO4) and purification by flash column chromatography (SiO2 pentane–Et2O) the corresponding alcohol. (MeLi treatment is not neccessary but advantageous since the tin halide formed is transformed to the corresponding methylated compound which is easily removed.) ¶ The relative configurations of the alcohols 7–10 and 18 were assigned by analogy to 6 based on the characteristic chemical shift of the hydrogen atom (of the major isomer) at the newly formed stereogenic center. · We believe that the products are formed under kinetic control; however Motherwell has shown that SO2 extrusion is rather slow in his systems and that in the biaryl synthesis the entire process is probably reversible [ref.6(c)]. Experiments to elucidate the mechanism are planned. 1 M. Shibasaki in Advances in Metal-Organic Chemistry ed. L. S. Liebeskind JAI Greenwich 1996 vol. 5 p. 119. 2 R. E. Gawley and J. Aubé in Principles of Asymmetric Synthesis ed. J. E. Baldwin FRS and P. D. Magnus FRS Pergamon 1996 p. 145; N. Krause Angew. Chem. Int. Ed. 1998 37 283. 3 L. Giraud E. Lacôte and P. Renaud Helv. Chim. Acta 1997 80 2148 and references cited therein. 4 E. Lee H. S. Whang and C. K. Chung Tetrahedron Lett. 1995 36 913. 5 E. Lee C. Lee J. S. Tae H. S. Wang and K. S. Li Tetrahedron Lett. 1993 34 2343; D. Crich and J.-T. Hwang J. Org. Chem. 1998 63 2765. 6 (a) S. Caddick K. Aboutayab K.Jenkins and R. I. West J. Chem. Soc. Perkin Trans. 1 1996 675; F. Aldabbagh and W. R. Bowmann Tetrahedron Lett. 1997 38 3793; (b) W. B. Motherwell and A. M. K. Pennell J. Chem. Soc. Chem. Commun. 1991 877; M. L. E. N. da Mata W. B. Motherwell and F. Ujjainwalla Tetrahedron Lett. 1997 38 137; (c) M. L. E. N. da Mata W. B. Motherwell and F. Ujjainwalla Tetrahedron Lett. 1997 38 141; E. Bonfand W. B. Motherwell A. M. K. Pennell M. K. Uddin and F. Ujjainwalla Heterocycles 1997 46 523. 7 H. J. Köhler and W. N. Speckamp J. Chem. Soc. Chem. Commun. 1980 142; D. L. Clive and T. L. B. Boivin J. Org. Chem. 1989 54 1997; J. Aubé X. Peng Y. Wang and F. Takusagawa J. Am. Chem. Soc. 1992 114 5466. 8 A. Studer M. Bossart and H. Steen submitted for publication. 9 R. S. Tipson J. Org. Chem. 1944 9 235. 10 P. Place M.-L. Roumestant and J. Goré Bull. Soc. Chim. Fr. 1976 169. 11 J. M. Brown and R. G. Naik J. Chem. Soc. Chem. Commun. 1982 348. 12 I. Fleming and J. J. Lewis J. Chem. Soc. Perkin Trans. 1 1992 3257. 13 D. P. Curran M-H. Chen and D. Kim J. Am. Chem. Soc. 1989 111 6265. Received in Cambridge UK 27th August 1998; 8/06718I Scheme 3 Reagents and conditions i Bu3SnSnBu3 (10%) hn ICH2CO2Et benzene (0.1 M); ii Bu3SnH AIBN syringe pump benzene (0.05 M) 2128 Chem. Commun. 1998

ISSN:1359-7345    

DOI:10.1039/a806718j

出版商:RSC    

年代:1998

数据来源: RSC