Kenn E. Harding

Stereoselective reactions of N-acyl-N,O-acetals with 2-(trimethysilyloxy)furan

Abstract Reactions of acyclic chiral N-acyl-N,O-acetals with 2-(trimethylsilyloxy)furan and BF 3 ·Et 2 O produces 4- (aminoalkyl)-2-buten-4-olides in 30% to 62% yield and variable diastereomeric excesses of the syn (threo) stereoisomer. Selectivity is dependent on the structure of N-acyl-N,O-acetal used.

1.9 – Electrophilic Heteroatom Cyclizations

This chapter on electrophilic heteroatom cyclizations covers reactions of carboncarbon π-bonds in which activation by an external electrophilic reagent results in addition of an internal heteroatom nucleophile. The general reaction is illustrated in Scheme 1. These cyclization reactions generate heterocyclic products, but many synthetic applications involve subsequent cleavage of the newly formed heterocyclic ring.

Acyclic stereoselection in α-amidoalkylation reactions

Abstract The chiral reagent 7 provides the first example of an acyclic α-amidoalkylation reagent that generates a new stereogenic center with excellent stereoselectivity, and the stereochemistry of the resulting products provides evidence that the N-acylimine intermediate reacts through the cisoid conformation 12 .

Stereoselective synthesis of (±)-erythro- and threo-γ-hydroxynorvaline

Abstract Both diastereomers of racemic γ-hydroxynorvaline were prepared from 4-penten-2-ol to illustrate a new general method for stereoselective synthesis of either erythro- or threo-1,3-amino alcohol systems from a single precursor.

Stereoselective conversion of allylic alcohols to n-acyl-trans-4,5-dialkyloxazolidines.

Abstract The stereoselective synthesis of N-acyl- trans -4,5-dialkyloxazolidines (precursors to threo -β-amino alcohols) through a procedure involving amidomethylation of a 2° allylic alcohol followed by mercuric-ion inititated cyclofunctionalization is reported.

Stereoselective Synthesis of γ-hydroxy-α-amino acids via intramolecular amidomercuration

Abstract A general method for the stereoselective conversion of homoallylic alcohols to erythro- or threo-β-hydroxy-α-amino acids is described. The key step is the stereoselective mercuric ion-initiated cyclofunctionalization of acylaminomethyl ether derivatives of the homoallylic alcohols (3 → 8). The stereochemistry of the products obtained from the cyclofunctionalization is controlled by the choice of reaction conditions. Reaction under conditions of kinetic control leads to predominant formation of cis 4,6-disubstituted tetrahydro-1,3-oxazines, while reaction under conditions which allow for equilibration of the organomercurial intermediates results in the formation of the trans stereoisomer with very high stereoselectivity. Oxidative demercuration and oxidation of the resulting alcohol produces a protected form of the title amino acids (8 → 9 → 10). Cleavage of the tetrahydrooxazine ring with hydrobromic acid then produces the amino acid products asγ-butyrolactone hydrobromides (11 and 12). This general method thus allows for stereoselective synthesis of either diastereomer of the amino acid product starting with a single homoallylic alcohol.

Selectivity in the amination of allylic alcohols via intramolecular amidomercuration

Abstract Intramolecular amidomercuration reactions of acylaminomethyl derivatives of γ-substituted allylic alcohols were examined. The effect of oxygen substitution on the δ carbon and of the geometry of the double bond on the regiochemistry and stereochemistry of the cyclization were established.

On the stereochemistry of biogenetic-like olefin cyclizations

Abstract An analysis of the potential involvement of alicyclic cations in biogenetic-like olefin cyclizations is presented. Application of the concepts of conformational analysis and transition state structures to the intramolecular attack of an olefinic double bond on a conformationally rigid cyclohexyl cation leads to the conclusion that such reactions should proceed with high stereoselectivity. A number of examples of cationic olefin cyclizations, including some undertaken specifically to test the theoretical analysis, are reviewed and discussed in relation to the potential involvement of alicyclic cations as intermediates in these cyclizations. This review illustrates some of the problems encountered in attempting to study mechanisms of olefinic cyclizations related to those involved in in vivo terpenoid biogenesis. The intervention of cyclohexenyl intermediates is implicated as a major cause of formation of large amounts of cis products in cationic olefin cyclizations. The results serve to demonstrate that intrinsic steric factors as well as stereoelectronic factors will favor stereoselective cyclization of polyolefins in enzymatically controlled olefin cyclizations as well as in vitro olefinic cyclizations.

Sequential chirality transfer in intramolecular amidomercuration reactions

Control of absolute stereochemistry in the amination of allyl alcohol is effected by transfer of chirality from a chiral auxiliary to the amidal carbon of an N-acylaminomethyl ether derivative, which upon intramolecular amidomercuration results in a second transfer of chirality to the new CN stereocenter.

Stereoselective synthesis of (±)-threo-γ-hydroxy-β-lysine lactone

Abstract A stereoselective synthesis of racemic threo-γ-hydroxy-β-lysine is reported. The threo aminoalcohol functionality is introduced by mercuric-ion initiated cyclofunctionalization of the acylaminomethyl ether 4a.