Preparation of New Chiral Building Blocks:  Highly Enantioselective Reduction of Prochiral 1,3-Cycloalkanediones Possessing a Methyl Group and a Protected Hydroxymethyl Group at Their C2 Position with Baker's Yeast or CBS Catalyst

Abstract

Highly enantioselective reduction of five-, six-, seven-, and eight-membered prochiral 1,3-cycloalkanediones possessing a methyl group and a protected hydroxymethyl group at their C2 position with baker's yeast or CBS catalyst and a new efficient and general method for preparing the 1,3-cycloalkanediones have been developed. These baker's yeast mediated reductions were found to produce corresponding ketols with high optical purity (>99% ee) and high yield. All of the prepared ketols and their derivatives, chiral building blocks, have been fully characterized, and their absolute configurations have been determined. These compounds would be useful for the convergent synthesis of complex natural products.

Saccharomyces cerevisiae: a potential stereospecific reduction tool for biotransformation of mono‐ and sesquiterpenoids

“…The use of baker's yeast as a stereospecific reduction biocatalyst has been well documented in the literature. Enantioselective reductions of various compounds, including dicarbonyl compounds (especially α‐ and β‐diketones, keto esters and cycloalkanediones)35, 40, 58, 60, 108, oxocarboxylic acids47, alkyl acetates23, 115 and aromatic ketones18, 67 have been successfully carried out, obtaining products with high enantiomeric excess (ee) in acceptable yields. It is widely used for the asymmetric reduction of prochiral ketones because such reductions with these microorganisms are readily executed and inexpensive.…”

“…However, one of the drawbacks of chemical processes is the formation of undesirable racemic mixtures that could only be avoided through the use of chiral building blocks suitable for the total synthesis of the target molecule. However, these building blocks could hardly be obtained from readily available compounds or natural products108.…”

Synthesis of Quaternary‐Carbon‐Containing and Functionalized Enantiopure Pentanecarboxylic Acids from Biocatalytic Desymmetrization of meso‐Cyclopentane‐1,3‐Dicarboxamides

“…For instance, ozonolysis of 8 followed by reduction15 gave rise to the formation of 2‐hydroxyethyl‐substituted dinitrile 14 in excellent yield. Dehydration16 of 14 gave a good yield of vinyl‐bearing dinitrile 15 , whereas palladium(II) I ‐effected isomerization17 of 8 resulted in the formation of 2‐ E ‐propenyl‐substituted dinitrile 16 almost quantitatively.…”

Copper(I)-Catalyzed Asymmetric Desymmetrization: Synthesis of Five-Membered-Ring Compounds Containing All-Carbon Quaternary Stereocenters

“…General Procedure 4; 2-(Benzyloxy)methyl-2-isopropyl-1,3-dioxolane gave the product (33% yield, BRSM) 1 H NMR (300 MHz, CDCl 3 )  0.89 (d, J = 6.9 Hz, 6H), 2.06 (sept, J = 6.9 Hz, 2H), 2.57-2.78 (m, 4H), 3.74 (s, 2H), 4.36 (s, 2H), 7.15-7.18 (m, 2H), 7.27-7.34 (m, 3H); 13 To a suspension of NaH (60 wt%, 240 mg, 6.0 mmol) and TBAI (185 mg, 0.5 mmol) in DMF (50 mL) were added a solution of (6-methyl-1,4,8,11-tetraoxospiro[4.1.4.2]tridec-6-yl)methanol [2] (1.15 g, 5.0 mmol) in CH 2 Cl 2 (5 mL) and PMBCl (749 L, 5.5 mmol) at 0 °C, and the reaction mixture was stirred for 12 h at room temperature. To a solution of 6-(p-methoxy)benzyloxy-6-methyl-1,4,8,11-tetraoxadispiro [4.1.4.2]tridecane (1.35 g, 3.85 mmol) in THF (20 mL) was added 1N HCl (20 mL) at room temperature, and the reaction mixture was stirred for 3 days at room temperature.…”