ChemInform Abstract: Ligand Assisted Nucleophilic Additions. Control of Site and Face Attack of Nucleophiles on 4‐Oxidoenones.

Abstract

ChemInform Abstract A properly positioned alkoxide-metal complex, possessing a transferable ligand, can exert a high degree of regio-and stereocontrol on the delivery of that ligand to a second reactive site. Thus, the complex (IV) generated from the quinone (I) undergoes Michael addition at the β-position of the unsaturated carbonyl functionality to give the product (V). Similarly, the use of such tandem 1,2/1,4-additions permits the preparation of products with defined stereochemistry such as (VIII) or (XII); the X-ray structure of (VIII) is determined. These conjugate addition processes are not restricted to the delivery of carbon nucleophiles; the alkoxyaluminum hydride complex derived from (XIV) and LiAlH4 delivers a hydride ion at the cis-position with regard to the OH moiety to give the product (XV).

Total Synthesis of (±)-Prostratin

“…In principle, a single nucleophilic addition to 8 could take place at the diastereotopic C8 and C11 positions (1,4-addition) or at C13 (1,2-addition), generating six possible regio-and/or diastereoisomers. Stimulated by the ligand assisted nucleophilic addition (LANA) method by Liotta and co-workers, 66 we first treated 8 with lithium hexamethyldisilazide (LiHMDS) to deprotonate the newly generated C9-hydroxyl group and then added methylmagnesium chloride to achieve the alkoxide-guided face selective 1,4-addition. Two separable diastereomers ($1:1 ratio, 73%) were isolated after silica gel column chromatography.…”