Polyoxygenated Tertiary Alcohols: A Kiyooka Approach

Abstract

A Kiyooka aldol approach for the stereoselective synthesis of tertiary alcohols is presented. This approach allows for the incorporation of different substituents at all three remaining positions at the chiral center bearing the tertiary alcohol. To demonstrate the validity of this approach different chiral alcohols were depicted and the relationship of double bond geometry of the ketene acetal and the diastereoselectivity was established.

Stereoselective Synthesis of Allylic Alcohols via Substrate Control on Asymmetric Lithiation

“…To investigate whether a coordinating protecting group (acetonide) would lead to similar results TIB esters 14 a, 15 a and the corresponding Cb analogs 14 b, 15 b were used in each case. TIB ester 14 a gave the formal Felkin products 20 a-23 a (Table 1, entries 1, 3, 5 and 7) with all vinyl boronic esters (16)(17)(18)(19) in very good to excellent selectivities (10 : 1-14 : 1) and excellent yields (72 %-97 %), regardless of their steric demand. The use of Cb analog 14 b (Table 1, entries 2, 4, 6 and 8) did not lead to the corresponding formal anti-Felkin products 20 b-23 b as main products, but instead also favored the formation of the formal Felkin products 20 a-23 a, albeit in lower selectivities (2 : 1-7 : 1) and yields (24 %-86 %).…”

“…In the case of the acetonide-protected anti-diketides (Table 2), TIB ester 15 a afforded formal Felkin products 24 a-27 a (Table 2, entries 1, 3, 5, and 7) with all four vinyl boronic esters (16)(17)(18)(19) in excellent selectivities (� 14 : 1) and very good yields (62 %-79 %). Cb analog 15 b, in contrast to the acetonideprotected syn-diketides (Table 1), afforded the corresponding formal anti-Felkin products 24 b-26 b (Table 2, entries 2, 4 and 6) with the sterically more demanding vinyl boronic esters 16-18.…”

“…The authors have cited additional references within the Supporting Information. [11][12][13][14][15][16][17][18]…”

Synthesis of Desepoxy‐Tedanolide C

“…We started the synthesis with the above described Kiyooka protocol (Scheme 1) to generate the tertiary alcohol. The so‐obtained product was protected as its PMP‐acetal 21 , [8b] which in turn was cleaved by DIBAL‐H reduction and the primary alcohol was Piv‐protected (Scheme 5). TBAF deprotection of the mixed acetal liberated aldehyde 22 which was used in the stereoselective addition of vinyl magnesium bromide to generate allylic alcohol 24 .…”

Copper-Catalyzed Asymmetric Oxidative Desymmetrization of 2-Substituted 1,2,3-Triols

“…Despite the great progress in the asymmetric synthesis of chiral tert -alcohols, − the efficient strategies to prepare enantiomerically enriched glycerol and related derivatives are still underdeveloped. Sharpless–Katsuki asymmetric dihydroxylation and asymmetric epoxidation-nucleophilic ring-opening sequence of 1,1-disubstituted olefins are powerful and reliable approaches to substituted glycerol derivatives. , Enantioselective aldol reactions of α-ketoesters and asymmetric substitution or oxidation reactions of malonate and β-ketoester derivatives would be alternative methods, though additional transformations are commonly required to obtain glycerol and their oxidized derivatives. In this context, the catalytic asymmetric desymmetrization of 2-substituted glycerols in a protecting-group-free fashion would be one of the most straightforward strategies to access chiral glycerol derivatives.…”