Stereoselective Synthesis of 1,2,3‐Triol Derivatives from α,β‐Unsaturated Acylsilanes

Abstract

The stereoselective synthesis of 1,2,3‐triol derivatives having contiguous stereogenic centers from α,β‐unsaturated acylsilanes 1 was described. The oxidation of an olefin moiety of 1 with osmium tetroxide proceeded smoothly to give the corresponding 2,3‐syn‐dihydroxyacylsilanes 2. The protection of two hydroxy groups of 2 followed by a nucleophilic reaction to the silyl carbonyl group gave the corresponding silylated triol derivatives (7 and 8) with high stereoselectivity, depending on the kind of nucleophilic reagents. The deprotection for 7 and 8 and the following protodesilylation gave two isomers of possible four 1,2,3‐triol derivatives. The stereoselective triol synthesis by asymmetric diolization of α‐silylated allyl alcohols 11 derived by nucleophilic addition to 1 was also investigated.

Catalytic Asymmetric Hydroalkoxylation and Formal Hydration and Hydroaminoxylation of Conjugated Dienes

“…The structure of compound 9 from a dihydroxylation of 3k was characterized by X-ray crystal analysis, which also sheds light on the absolute configuration of 3k . Previously, a seven-step synthetic route was required to prepare the racemic triol compound 10 from an unstable enol silyl ether (Scheme b) . In comparison, a simple sequential hydration and dihydroxylation from the abundant diene substrate could furnish the optically active triol 10 in high efficiency.…”

“…Previously, a seven-step synthetic route was required to prepare the racemic triol compound 10 from an unstable enol silyl ether (Scheme 5b). 80 In comparison, a simple sequential hydration and dihydroxylation from the abundant diene substrate could furnish the optically active triol 10 in high efficiency. In particular, a stereodivergent synthesis of four challenging triol stereoisomers of 10 was easily achieved by exerting precise stereocontrol in each step independently (Scheme 5b).…”

Mn(I)-Catalyzed Carbon-Skeleton Rearrangement of Tertiary Alcohol-Based Aldol Reaction with Aldehydes

“…Silylation of Ketone 3−1. 16 To a solution of 3−1 (31 mg, 0.10 mmol) and trimethylsilyl chloride (21 mg, 0.20 mmol) in 0.5 mL of THF was added TMPMgCl•LiCl in THF (1.0 M, 0.40 mmol) dropwise, and the mixture was stirred for 36 h at 0 °C. After this period, water was added to the mixture, which was then extracted three times with Et 2 O.…”

Synthesis of Chiral Acyclic Nucleosides by Sharpless Asymmetric Dihydroxylation: Access to Cidofovir and Buciclovir

“…Under 2 mol % K 2 OsO 2 (OH) 4 and 10 mol % L2 , the SAD reaction of 1l proceeded smoothly, affording 0.32 g (88% yield) of the diol 2l with 95% ee. Addition of TBAF resulted in the removal of the TMS group in diol 2l , affording the Bz-protected N 1 -(2,3-dihydroxy­propyl)­cytosine 2a in 73% yield and 95% ee, which could be transformed into the drug ( S )-Cidofovir (Scheme a). Compared to work by the Bronson group to construct Bz-protected-N 1 -(2,3-dihydroxy­propyl)­cytosine 2a in two steps with a 36% total yield, our developed route could afford a 64% total yield in two steps.…”

“…The absolute configuration of product 2a was determined to be the ( S )-configuration by comparison with the reported optical rotation. With the chiral acyclic purine nucleoside 6e as the starting material in hand, the triethylsilyl group could also be removed by treatment with TBAF, affording the chiral diol 7e in 62% yield and 95% ee. After hydrolysis, ( R )-Buciclovir could be obtained in 91% yield (Scheme b).…”