The application of a mechanistic model leads to the extension of the Sharpless asymmetric dihydroxylation to allylic 4-methoxybenzoates and conformationally related amine and homoallylic alcohol derivatives.

Abstract

The scope and utility of the Sharpless asymmetric dihydroxylation has been expanded to include the use of allylic 4-methoxybenzoates as precursors of a wide variety of substituted chiral glycerol derivatives. The allylic 4-methoxybenzoyl group was found to be superior to other allylic alcohol protecting groups with respect to both yield and enantiomeric purity of the product. For example, asymmetric dihydroxylation of allyl 4-methoxybenzoate (6a) using the (DHQD)2PYDZ*Os04 (1.0~04) catalyst system affords (S)-3-(4-methoxybenzoyloxy)-1 ,Zpropanediol (7a) in '99% yield and 98% ee. The 4-methoxybenzoates of a variety of other allylic alcohols also serve as excellent substrates, in contrast to the parent alcohols themselves. The efficient asymmetric dihydroxylation of homoallylic 4-methoxyphenyl ethers (12a and 15), allyl 9-fluorenimine (18b), bis(homoally1) 4-methoxybenzoate (14) and other structurally related substrates is also described. This methodology was developed under mechanistic guidance from the transition state model advanced earlier by us for the bis-cinchona alkaloid catalyzed asymmetric dihydroxylation reaction. The 4-methoxybenzoyl group functions not only to selectively protect one of the hydroxy groups of the product triol for subsequent synthetic manipulation but also to provide an extended binding group that participates in hydrophobic and aryl-aryl interactions with the U-shaped binding pocket of the (DHQD)2PYDZ*Os04 catalyst (laOs04), thereby enhancing enantioselectivity.

Total synthesis and absolute configuration of avenolide, extracellular factor in Streptomyces avermitilis

“…Subsequent Sharpless dihydroxylation 9,10 using (DHQ) 2 PHAL as a chiral ligand afforded 5 (93% ee). [11][12][13] (The enantiomeric excess was determined by chiral HPLC analysis (condition: DAICEL CHIRAL-PAK AS-3 (0.46 cm fÂ25 cm), 3:1 hexanes/2-propanol mobile phase (flow rate at 1.0 ml per min) and detection at 254 nm (room temperature, rt)). Tosylation of the primary alcohol followed by a substitution reaction with Me 2 CuCNLi 2 and methanolysis gave diol 6.…”

Total synthesis of diastereomeric marine butenolides possessing a syn-aldol subunit at C10 and C11 and the related C11-ketone

“…The iodide 5 used in our previous work was of 82% ee according to the enantioselectivity of the asymmetric dihydroxylation (see 8 and 9 in Supplementary data). 10 For obtaining accurate optical rotation data of the diastereomers of 1 and 2, an alternative synthesis of 5 from the enantiomerically pure 10 is employed in the current work. We report here on total synthesis of 1c and 1d and the C10 epimers 2a and 2b starting from the alcohols 12c and 12d, which are readily derived from the syn-selective aldol reaction 11 of the norephedrine-derived chiral propionates (1S,2R)-13 and (1R,2S)-13, respectively.…”

From 3,3,4,4-tetraethoxybutyne to carbohydrate mimics

“…When the ester was reacted, however, dihydroxylation took place, but the PMBz protection was not stable enough to prevent cyclization and hemiketal formation. Spectroscopic studies reveal the presence of one PMBz-protected hemiacetal only, conceivably the isomer depicted in Scheme 12, which might indicate that acyl migration takes place during the oxidation process [19]. The mechanism for this transformation is currently under investigation.…”

“…The effect of such protection has so far been investigated for three protected analogues of one compound only, viz. the tetrahydropyranyl (THP) and benzyl (Bn) ethers as well as the p-methoxybenzoate (PMBz) of 1,1-diethoxy-5-hydroxypent-3E-en-2-one (19). When these derivatives of 19, all prepared in excellent yield by standard methods (Scheme 12), were treated with Sharpless' AD-mix α under standard conditions, somewhat surprising results were obtained.…”