Polysubstituted Oxygen Heterocycles by a Reformatsky-Type Reaction/Reductive Cyclization Approach from Enantiopure β-Ketosulfoxides

Abstract

The stereoselective synthesis of tetrasubstituted tetrahydrofurans and trisubstituted tetrahydropyrans bearing a sulfoxide was achieved by reductive cyclization (Et3SiH/TMSOTf) from the corresponding enantiopure hydroxy ketones protected as a dioxolane. These derivatives are easily accessible from a Reformatsky-type reaction between alpha-bromo-alpha'-sulfinyl ketones and protected alpha- or beta-ketoaldehydes, followed by diastereoselective reduction of the resulting beta-ketosulfoxide.

Asymmetric Total Synthesis of Cladosporin and Isocladosporin

“…The ring-opening of epoxide 21 , deprotection of the 1,3-dithiane group with I 2 , and Me 4 NBH(OAc) 3 reduction of β-hydroxy ketone 12 gave the desired 1,3- anti -diol 11 . Then we turned to the reductive cyclization of hydroxy dioxolanes developed by Colobert and co-workers . Treatment of 11 with an excess of Et 3 SiH (5 equiv), followed by TMSOTf (1.3 equiv) in CH 2 Cl 2 at 0 °C, led to the rapid (within 30 min) formation of the 2,6- cis -THP derivative cis - 4 as a sole diastereomer.…”

Stereoselective Synthesis of 2H‐Chromans by Reductive Deoxygenation of Differently Substituted 2‐Sulfinylmethylchroman‐2‐ols

“…Among the strategies available nowadays for the stereoselective synthesis of cyclic ethers, [15] the Et 3 SiH/TMSOTf-promoted synthesis of ethers by reductive condensation of carbonyl compounds and alkoxysilanes [16] or alcohols [17] has been applied by us to the asymmetric synthesis of a number of different sized systems. Thus, the Et 3 SiH/TMSOTf-promoted reductive cyclization of enantiopure β-hydroxy sulfinyl ketones I (Scheme 1), in turn accessible by the well-established diastereoselective reduction of a suitably functionalized enantiopure β-keto sulfoxide, [18] allowed the synthesis of five-, [19] six-, [19][20][21] seven- [22] and eight-membered [23] cyclic ethers with 2,ω-cis-disubstitution (II) in a highly diastereoselective manner. We tested the validity of our asymmetric Scheme 1.…”

General Access to Concave-Substituted cis-Dioxabicyclo[3.3.0]octanones: Enantioselective Total Syntheses of Macfarlandin C and Dendrillolide A

“…3-Methylcyclohexenone (39) (1.02 mL, 9 mmol) was added dropwise at 0 °C and stirring was continued for 30 min until TLC showed full consumption of the starting material. The reaction was then cooled to −78 °C, and a solution of aldehyde 40 (1.93 g, 14.8 mmol, 1.65 equiv) 43 in Et 2 O (15 mL) was added slowly. The reaction was allowed to warm to rt overnight.…”