Indium‐Mediated Regio‐ and Diastereoselective Reduction of Norbornyl α‐Diketones

Abstract

A novel, efficient, and regio- as well as diastereoselective conversion of non-enolizable bicyclic alpha-diketones into synthetically useful acyloins mediated by indium metal is described. The reduction is highly diastereoselective, leading exclusively to endo-acyloins (endo-hydroxyl groups) in excellent yields, and tolerates a variety of sensitive substituents, such as acetate, ester, and bridgehead halogens. The regioselectivity in the reductions of monosubstituted alpha-diketones varied from 70:30 to 100:0 for the two possible isomeric alcohols. The methodology is extended to the synthesis of highly functionalized cyclopentane carboxaldehydes, potential building blocks in organic syntheses, by cleavage of the acyloins by treating them with Pb(OAc)4 in MeOH/PhH. Allylindium additions to carboxaldehydes 22 have been found to be highly diastereoselective.

Organoindium Reagents: The Preparation and Application in Organic Synthesis

“…When highly functionalized chiral cyclopentane carboxaldehydes were exposed to indium-mediated allylation in DMF, an allylation–lactonization sequence occurred to deliver seven-membered lactones in nearly quantitative yields as single diastereomers (Scheme ) . A transition state involving the chelation of allylindium reagent with the OMe and OEt groups was invoked to account for the excellent diastereoselectivity observed.…”

“…When highly functionalized chiral cyclopentane carboxaldehydes were exposed to indium-mediated allylation in DMF, an allylation−lactonization sequence occurred to deliver sevenmembered lactones in nearly quantitative yields as single diastereomers (Scheme 175). 377 A transition state involving the chelation of allylindium reagent with the OMe and OEt groups was invoked to account for the excellent diastereoselectivity observed. Canac, Levoirier, and Lubineau developed a novel method for the synthesis of C-branched sugars or C-disaccharides by using enantiopure 4-bromo-2-enopyranoside as the allylation agent (Scheme 176).…”

Oxone-Mediated Oxidative Cleavage of β-Keto Esters and 1,3-Diketones to α-Keto Esters and 1,2-Diketones in Aqueous Medium

“…α-Keto esters and 1,2-diketones are very useful compounds for the synthesis of various pharmaceuticals and other organic molecules. They are extensively used as starting materials for intercalation reactions, − the synthesis of carboxylic acids and heterocyclic compounds, the asymmetric synthesis of α-hydroxy ketones, − of acyloins, and the direct synthesis of substituted indoles . 1,2-Diketones have also shown interesting applications as photosensitive agents and photoinitiators. , The practical and efficient synthesis of α-keto esters and 1,2-diketones remains an interesting and challenging goal.…”

A Rapid and Stereoselective Route to the trans-Hydrindane Ring System

“…The precursor endo -homoallyl alcohol 1 could be easily prepared by allylation of aldehyde 4 by any suitable allyl organometallic reagent. Attracted by indium-mediated reactions which have gained increasing importance recently due to their mild nature, functional group tolerance, high stereoselectivity, ease of handling, compatibility with water as a solvent, and insensitivity to air, and also due to our own interest in indium chemistry, we decided to use allylindium reagent for this purpose. Indium-mediated allylation of the aldehyde 4 was performed with different solvent systems (eq 1, Table ).…”