The acyl-Claisen rearrangement: development of a novel metal-catalyzed Claisen rearrangement and enanitoselective variants of the acyl-Claisen rearrangement

Citation

Yoon, Tehshik Peter (2002) The acyl-Claisen rearrangement: development of a novel metal-catalyzed Claisen rearrangement and enanitoselective variants of the acyl-Claisen rearrangement. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechTHESIS:01282010-153053761

Abstract

The development of a versatile new variant of the Claisen rearrangement is described. In this new Lewis acid-catalyzed process, the condensation of an allylic amine with a ketene (generated in situ from dehydrohaolgenation of an acid chloride) results in formation of a zwitterionic intermediate. Sigmatropic rearrangement via a highly organized cyclic transition state allows stereospecific access to a diverse range of α,β-disubstituted-γ,δ-unsaturated amides in excellent yields and diastereoselectivities for a range of alkyl-, aryl-, and heteroatom-substituted substrates. The ability of this new methodology to generate quaternary carbon stereocenters on both cyclic and acyclic carbon frameworks is demonstrated. An enantioselective variant of the acyl-Claisen rearrangement employing a chiral magnesium(II)-bis(oxazoline) Lewis acid has been developed. The use of chelating acid chlorides provides excellent organizational control over the transition state, allowing the rearrangement of a range of allyl morpholine substrates to proceed in up to 97% ee. Excellent levels of complementary diastereocontrol can be achieved in a predictable and highly selective manner from the rearrangement of the (E)- and (Z)-isomers of the allyl amine substrates. This reaction is also proficient at accessing quaternary carbon stereocenters. The scope of the enantioselective acyl-Claisen has been expanded by the use of a new chiral boron Lewis acid. This rearrangement does not require chelating acid chloride substrates for good enantioinduction. Thus, a range of α-alkyl-, α-alkoxy-, α-thio-, and α-halogen-substituted Claisen adducts can be produced in up to 93% ee.

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