Regio‐, Diastereo‐, and Enantioselective Synthesis of vic‐Diols via α‐Silyl Ketones According to the SAMP/RAMP Hydrazone Method

Abstract

L-Selectride reductions a-Silylated ketones 5 or 10 of high enantiomeric purity (ee 2 goo/,) are easily available by silylation or silylation/alkylation of ketones 1 or 6, resp., according to the SAMP/RAMP hydrazone method. Reduction of 5 or 10 with L-selectrideg, followed by oxidative cleavage of the C-Si bond, leads to vic-diols 11 -13 with high diastereoselectivity (de 2 90%) and without racemization. The stereoselectivity of the reduction depends on the structure of the a-silyl ketones 5 or 10, the reducing reagents, and the solvents used.Asymmetric synthesis of uic-diols has recently received considerable attention, because vic-diols are common structural features of many natural products'), useful chiral building blocks in the synthesis of biologically active compounds'), and valuable intermediates in a variety of synthetic transformations ' 1.These approaches have been carried out by enantioselective ring opening by epoxide hydrase4', ring opening by diastereoselective epoxidation of chiral allylic alcohols "chiral pool" syntheses from natural products6) including diastereoselective 1,2-additions of organometallics to a-alkoxy aldehydes &), stereospecific coupling of chiral boronic esters with chiral lithio esters followed by hydrolysis7), homologation of alkylboronates followed by hydrolysis *), and asymmetric osmylation of olefins with chiral amines as ligands'). On the other hand, stereoselective reductions to form uicdiols have also been described based on diastereoselective reduction of a-hydroxy ketones'"), but little attention has been paid to enantioselective syntheses of vic-diols by enantio-and diastereoselective reductions, although in the realm of aliphatic ketones efficient techniques") are now at hand to selectively introduce stereocenters on acyclic carbon chains '*). Therefore, the development of still more versatile and effective diastereo-and enantioselective syntheses of uic-diols is of considerable interest.In continuation of our efforts to further explore the utility of the SAMPIRAMP hydrazone method13), we now report on a convenient synthesis of vic-diols with high regio-, diastereo-and enantioselectivity. Enantioselective Synthesis of a-Silyl Ketones 5 and 10 a-Silyl Ketones 5 and 10 were synthesized from symmetrical dialkyl ketones 1 or unsymmetrical methyl alkyl ketones 6 according to Schemes 3 and 4.Symmetrical dialkyl ketones 1, after conversion into their corresponding SAMP hydrazones (S)-2, are metalated with lithium diisopropylamide and then a-C-silylated with isopropoxydimethylsilyl chloride.The a-silylated SAMP hydrazones 3 (de 2 90%) thus obtained are cleaved oxidatively and free of racemization with ozone affording, after chromatographic separation of (S)-4 (recycling of the chiral auxiliary), the ct-silyl ketones (R)-5 of high enantiomeric purity

Enantioselective Synthesis of Vicinal ( R , R )-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase

“…The 1 H and 13 C NMR spectra of chemically prepared 2,3-pentanediol showed the presence of two diastereoisomers, (2RS,3RS) and (2RS,3SR) in their racemic forms, showing a good agreement with NMR data described before (31). Thus, the pair (2R,3S) plus (2S,3R) [abbreviated (2RS,3SR)] showed the chemical shifts at ␦ 3.81 ppm (for H-2), ␦ 3.55 (for H-3), ␦ 1.15 (for H-1), and ␦ 1.00 (for H-5) (see Fig.…”

Regio‐ and Stereoselective Reduction of Diketones and Oxidation of Diols by Biocatalytic Hydrogen Transfer

“…The commercial mixture of meso ‐2,5‐hexanediol ( meso ‐ 5c ) and rac ‐2,5‐hexanediol [(2 R *,5 R *)‐ 5c ] was separated by silica gel chromatography (toluene/EtOAc = 1:1). The following all ‐ rac ‐diols were obtained by reduction of the corresponding diketone with the appropriate amount of NaBH 4 in EtOH as described previously,8a and the products were identified by comparison of the NMR data with that from the literature: 2,3‐pentanediol 1c ,15 2,3‐heptanediol 2c ,16 and 3,4‐hexanediol 4c 17. Diols (2 R *,3 R *)‐ 6c and (2 R *,3 S *)‐ 6c were synthesized as described starting from E ‐ and Z ‐2‐octene, respectively 18…”

Stereochemical Control in Organic Synthesis Using Silicon-Containing Compounds

“…However, the transition structure based on the Felkin−Anh model appears to be surprisingly sensitive to the length of the carbon chains on the ketone, with the α-silyl ketone 1563 giving, with just as good selectivity, the anti alcohol 1564 , and hence the anti diol 1565 . The temperature and the reducing agent have a large effect on the degree of selectivity, and the presence or absence of Lewis acids also affects its sense (Scheme ) 380 …”