Synlett
DOI: 10.1055/s-0036-1588805
cluster
© Georg Thieme Verlag Stuttgart · New York

Bu4N+-Controlled Addition and Olefination with Ethyl 2-(Trimethylsilyl)acetate via Silicon Activation

Manas Dasa, Atul Manvara, Ian Foxa, b, Dilwyn J. Robertsb, Donal F. O’Shea*a
  • aDepartment of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2, Ireland   Email: donalfoshea@rcsi.ie
  • bIpsen Manufacturing Ireland Ltd, Blanchardstown Industrial Park, Blanchardstown, Dublin 15, Ireland
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Publication History

Received: 30 January 2017

Accepted after revision: 27 March 2017

Publication Date:
02 May 2017 (eFirst)

Published as part of the Cluster Silicon in Synthesis and Catalysis

Abstract

Catalytic Bu4NOAc as silicon activator of ethyl 2-(trimethylsilyl)acetate, in THF, was utilized for the synthesis of β-hydroxy esters, whereas employing catalytic Bu4NOTMS gave α,β-unsaturated esters. The established reaction conditions were applicable to a diverse range of aromatic, heteroaromatic, aliphatic aldehydes and ketones. Reactions were achieved at room temperature without taking any of the specialized precautions that are in place for other organometallics. A stepwise olefination pathway via silylated β-hydroxy esters with subsequent elimination to form the α,β-unsaturated ester has been demonstrated. The key to selective product formation lies in use of the weaker acetate activator which suppresses subsequent elimination whereas stronger TMSO activator (and base) facilitates both addition and elimination steps. The use of tetrabutyl ammonium salts for both acetate and trimethylsilyloxide activators provide enhanced silicon activation when compared to their inorganic cation counterparts.

Supporting Information