Synthesis, properties and applications of chiral allenylindium reagents

Lewis Acid promoted additions of chiral allenylstannanes to aldehydes provide a means to stereoselectively synthesize acyclic compounds with multiple contiguous stereocenters. These organostannane reagents produce adducts with high regio-, diastereo-, and enantioselectivity. However, there are safety concerns associated with using trialkyltin reagents. This endeavor examines our efforts to develop enantioenriched allenylindium reagents as an effective alternative to the existing allenyltin reagents. These allenylindium reagents are derived from either enantioenriched allenyl halides or propargylic mesylates. The mesylate-derived reagents are formed through a transient allenylpalladium species and are superior, in terms of enantioselectivity, to the halide-derived reagents. The reagents derived from chiral mesylates consistently add to aldehydes to produce adducts with >90% ee. The diastereoselectivity of these reactions is dependant on the type of aldehyde used with the additions to branched aldehydes yielding a diastereomeric ratio >95:5. Additions to chiral aldehydes are highly reagent control and have been employed in the construction of stereotriad subunits of polyketide natural products. Additional applications of this novel methodology are investigated including additions to complex stereotriad and epoxy aldehyde substrates.; Overall, these mild, less toxic, and conveniently prepared reagents are comparable to the existing allenylstannane reagents. The Pd/In methodology is also applicable to other propargyl and allylic substrates.