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Article

In- or In(I)-Employed Tailoring of the Stereogenic Centers in the Reformatsky-Type Reactions of Simple Ketones, α-Alkoxy Ketones, and β-Keto Esters

Supporting Info

Srinivasarao Arulananda Babu, Makoto Yasuda, Ikuya Shibata, and Akio Baba*

Department of Applied Chemistry and Handai Frontier Research Center, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

J. Org. Chem., 2005, 70 (25), pp 10408–10419

DOI: 10.1021/jo051659w

Publication Date (Web): November 10, 2005

To whom correspondence should be addressed. Tel: +81-6-6879-7384. Fax: +81-6-6879-7387.

, baba@chem.eng.osaka-u.ac.jp

Abstract

Comprehensive studies were carried out on efficient In- or In(I)-based diastereoselective Reformatsky-type reactions of simple ketones, α-alkoxy ketones, and β-keto esters. High anti selectivity was established in the addition of the branched α-halo ester derivatives to simple ketones using indium metal under THF-refluxing conditions. The stereochemistry undoubtedly indicated that the involvement of a cyclic transition state, formed from the ketone and stereochemically preferred transient E-enolate derived from the branched α-halo ester. Next, with the view of tailoring high degree of stereoselection, the concept of chelation-controlled addition of indium enolates was envisioned. In this line, marvelously syn selective additions to α-alkoxy ketones and β-keto esters were established. Interestingly, these diastereoselective additions to α-alkoxy ketones and β-keto esters require either In(I)X or In−InCl₃ systems in toluene under ultrasonication, while very poor efficiency and diastereoselectivity were obtained using indium metal or THF as solvent. The stereochemistry of key products was unambiguously determined by the single-crystal X-ray structure analyses. On the basis of the observed astonishing diastereoselectivities due to strong chelation plausibly, a low-valent RIn(I)-type transient spices could be projected as very reactive spices in the Reformatsky-type reactions.

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