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

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.