Stereoselective 1,4-Phenyl Migration from Silicon to Carbon in α-Siloxy Cyclic Acetal Systems: A Concise Synthesis of 1,2-cis-Phenyl C-Glycoside and Enantioenriched Silanol

Abstract

The treatment of O-glycoside with alcohol in the presence of montmorillonite K10 clay and 4-Å MS yields the 1,4-aryl migration product with a 1,2-cis-phenyl C-glycoside scaffold and a chiral silyl moiety with high stereoselectivity.Aryl C-glycosides constitute an important class of the Cglycoside family of natural products and have attracted considerable interest because of their diverse biological activities and resistance to acidic and enzymatic hydrolysis. 1 Therefore a number of methods have been developed for the stereoselective formation of the aryl C-glycoside linkage. 2 Among these methods, the reactions of glycosyl donors by intermolecular Friedel-Crafts couplings or by reactions with aryl metal reagents have been well established and these reactions yielded 1,2-trans-aryl C-glycosides, predominantly. In contrast, access to the thermodynamically more unfavorable 1,2-cis-aryl C-glycosides remains relatively undeveloped. 3 To this end, we have recently reported that montmorillonite K10 clay promoted 1,4-aryl or alkenyl migration from silicon to the C1 carbon in cyclic N,O-acetal systems. 4-6 The unique features of this reaction are as follows: (i) the aryl or alkenyl group on the siloxy group migrates intramolecularly in a cis fashion, and (ii) a concomitant nucleophilic substitution of the alkoxy group on the silicon atom proceeds with high stereoselectivity. On the basis of this result, we envisioned that a similar aryl migration of O-glycoside A with a tert-butyldiphenylsilyl group at the C2 hydroxyl group could afford the phenyl C-glycosides B in a 1,2-cis fashion (Scheme 1). Desilylation of B would provide C2 hydroxy phenyl C-glycoside C. Furthermore, the treatment of phenyl C-glycosides B with a base would cause b-elimination and provide enantioenriched silanols D, which are otherwise difficult to obtain. Here, we report the details of the aryl migration in cyclic acetal systems, which provide an effective approach to the stereoselective synthesis of 1,2-cis-phenyl C-glycosides as well as chiral silanol.At the outset, we attempted the phenyl migration of the simple five-membered cyclic hemiacetal 1a with the (tertbutyldiphenylsilyl)oxy group at the C2 position; the cyclic hemiacetal 1a was easily prepared from commercially available (S)-a-hydroxy-g-butyrolactone (97% ee) in two steps [(i) TBDPSCl, imidazole and (ii) DIBAL]. The reaction was performed according to the previously developed protocol; the cyclic hemiacetal 1a was treated with two equivalents of benzyl alcohol in the presence of K10 and 4-Å MS in CH 2 Cl 2 at 0 °C for 12 hours, providing the corresponding aryl migration product 2 in 71% yield with 90% diastereomeric ratio (Scheme 2). 7,8 Some of the aryl migration product 2 may be produced through benzyl acetal 1b; indeed a similar reaction of separately prepared 1b 9 also provided 2 in 46% yield with 90% dr.The exposure of the phenyl migration product 2 to TBAF afforded alcohol 3a as a single diastereomer, which means that the diastereomer of 2 is derived from the silicon stereocenter. T...

A Silicon‐Stereogenic Silanol ‐18O‐Isotope Labeling and Stereogenic Probe Reveals Hidden Stereospecific Water Exchange Reaction

“…Therefore, the synthetic access is challenging. [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ] Although the documented synthetic strategies provide access to chiral silanols, many works focus on the synthetic aspect, while studies on the stability and subsequent chemistry of these components are still underrepresented. These are important for silanols, since the configuration of silanols in solution is not necessarily stable, as described for a bioactive silanol, documenting a racemization of the Si‐chiral compounds in aqueous medium.…”

Single-Atom Ligation of Four Different Alcohols at One Silicon Center: Methodology Development and Proof of Concept

“…Unfortunately, the dr for 67 and 69 was near 1:1 using 2-octanol as auxiliary. Efforts to improve the stereo-control using other chiral auxiliaries are underway (26,27). The mono-specific ligation of HFIP was also true for the TBDPS ether 70, TBDPSOH 77, and TPS ether 80, yielding 71, 78, and 81 respectively.…”