Practical and Robust Method for Regio- and Stereoselective Preparation of (E)-Ketene tert-Butyl TMS Acetals and β-Ketoester-derived tert-Butyl (1Z,3E)-1,3-Bis(TMS)dienol Ethers

Abstract

We developed an efficient, practical, robust method for the regio- and stereoselective preparation of (E)-ketene trimethylsilyl acetals (KSAs) derived from tert-butyl esters 1. The reaction was performed under convenient reaction conditions; LDA-TMSCl, 0-5 degrees C, and cyclopentyl methyl ether (CPME) solvent. Two kinds of (Z)- and (E)-KSAs derived from alpha-oxygen and alpha-nitrogen-substituted tert-butyl esters, respectively, were also obtained in good yield. The present protocol was successfully applied to a stereocontrolled preparation of useful, but highly reactive (less accessible) beta-ketoester-derived tert-butyl (1Z,3E)-1,3-bis(TMS)dienol ethers 2.

Cyclopentyl Methyl Ether: An Elective Ecofriendly Ethereal Solvent in Classical and Modern Organic Chemistry

“…Okabayashi and co‐workers have screened the influence of different ethereal solvents such as Et 2 O, THF, dioxane, and DME in the regio‐ and stereoselective preparation of synthetically valuable intermediates such as ( E )‐ketene trimethylsilyl acetals (KSAs) starting from tert ‐butyl esters in the presence of lithium diisopropylamide (LDA)/TMSCl at 0–5 °C (Scheme ) . The stereochemistry ( E / Z ) of the KSAs, which subtly depends on the molar ratio, temperature, and solvent, is fundamental, because it profoundly affects the subsequent diastereo‐ and enantioselective C−C bond‐forming events.…”

“…Okabayashi and co-workers have screened the influence of different ethereal solvents such as Et 2 O, THF,d ioxane, and DME in the regio-and stereoselective preparation of synthetically valuablei ntermediates such as (E)-ketene trimethylsilyl acetals (KSAs) starting from tert-butyl esters in the presence of lithium diisopropylamide (LDA)/TMSCl at 0-5 8C( Scheme 10). [24] The stereochemistry (E/Z)o ft he KSAs, which subtly depends on the molar ratio, temperature, and solvent, is fundamental, because it profoundly affectst he subsequentd iastereo-and enantioselective CÀCb ond-forminge vents. Therefore, the use of as uitable reactiont emperature range,f rom À20 to 20 8C, and considering that ab ulky tert-butyl group would be useful to enhancet he E selectivity,t he best result in terms of both yield and regioselectivity is achieved with CPME,w hereas Et 2 O, THF,d ioxane, and DME providep oor regioselectivity,t hus promoting undesirable C-silylation.…”

Hydrolysis of Diazonium Salts Using a Two‐Phase System (CPME and Water)

“…CPME has recently received much attention because of high boiling point (106°C), resistance to peroxide formation, extremely easy dehydration, and high solubility with organic compounds. Also, CPME is applicable for a variety of synthetic methods using organolithium reagents, Grignard reactions, and various cross‐coupling reactions in the presence of Pd catalysts .…”

Studies toward welwitindolinones: formal syntheses of N-methylwelwitindolinone C isothiocyanate and related natural products

“…Treatment of 54 with 2 equiv of NaHMDS and TMSCl in cyclopentyl methyl ether (CPME) gave 55 as a single isomer. 18 Owing to its lability, 55 was coupled directly without purification with 25 in the presence of TMSOTf to deliver the requisite ketoester 42 in 60% over two steps. This outcome was significant for two reasons.…”