Laurence M. Harwood

The direct synthesis of the cyclic sulphamidate of (S)-prolinol: SimultaneousN-protection and activation towards nucleophilic displacement of oxygen.

Abstract The preparation of the cyclic sulphamidate of (S)-prolinol has been achieved by reaction with sulphuryl chloride at low temperature. This material has been shown to be susceptible to acid catalysed nucleophilic attack to furnish 2-(NN-dialkylamino)methyl- and 2-(methoxymethy]pyrrolidines after hydrolysis of the intermediate sulphamic acid derivatives.

A general procedure for the synthesis of isoxazolidin-5-ones

Abstract Conjugate addition of N-substituted hydroxylamines to α,β-unsaturated esters followed by cyclisation of the adducts with lithium bis (trimethylsily)amide provides the first general means of synthesising isoxazolidin-5-ones, the N-benzyl derivatives of which may be hydrogenolised to β-aminoacids.

Development of chiral stabilised azomethine ylids: A chiral memory relay system.

Abstract Chiral, stabilised azomethine ylids incorporated in cyclic templates derived from ( R )- or ( S )-2-phenylglycinol and ( S )-valine undergo enantioselective 1,3-dipolar cycloaddition reactions with a variety of dipolarophiles. Removal of the template in the case of adducts derived originally from ( S )-valine furnishes enantiomerically pure α-substituted proline derivatives.

Development of a chiral stabilised azomethine ylid. A chiral relay system.

Abstract The chiral, stabilised azomethine ylid ( 2 ) derived from ( R )-2-phenylglycinol has been demonstrated to undergo enantioselective 1,3-dipolar cycloaddition reactions with a range of alkene and alkyne dipolarophiles.

The high pressure mediated intramolecular Diels-Alder reaction of furan dienes: a synthetic approach towards daphnanes

Abstract Furan 2 undergoes intramolecular Diels-Alder reaction when subjected to high (14kbar) pressures to give a mixture of endo and exo adducts in which the exo adduct is formed as the kinetic product, at variance with the expected course of events.

Enantiocontrolled construction of bicyclic proline derivatives via one-pot generation and intramolecular trapping of chiral stabilised azomethine ylids

Abstract Aldehydes possessing unsaturation at C-5 or C-6 condense with (5 S )-phenylmorpholin-2-one ( 1 ), generating chiral stabilised azomethine ylids which undergo concommitant diastereospecific intramolecular 3+2 dipolar cycloaddition to furnish adducts ( 2 ), ( 4 ), and ( 5 ) which may be converted to homochiral bicyclic proline derivatives. Reductive desulfurisation of the thioether derivative ( 5 ) leads to (2 S ,4 R ,5 R )-4,5-dimethylproline ( 7 ).

Development of chiral stabilised azomethine ylids: completing the memory relay

Abstract We report how the α-chirality of L-valine can be “memorised” through a sequence involving chirality transfer to a cyclic template, followed by azomethine ylid generation and enantiospecific cycloaddition to regenerate the centre lost during ylid formation. Subsequent removal of the chiral template furnishes α-substituted D-proline derivatives.

Asymmetric cycloadditions of aldehydes to stabilised azomethine ylids: Enantiocontrolled construction of β-hydroxy-α-amino acid derivatives

Abstract In the absence of added dipolarophile, chiral stabilised azomethine ylids derived from the reaction of 5-( S )-phenylmorpholin-2-one ( 1 ) with aldehydes undergo efficient and highly enantiocontrolled cycloaddition with a second molecule of aldehyde to furnish products which may be converted into β-hydroxy-α-amino acids.

Synthesis of homochiral α-amino acids by reductive amination of α-ketoacids via 3-substituted- 5-phenyl-3,4-dehydromorpholin-2-ones: Synthesis of (S)- and (R)-2-aminobutanoic acid

Abstract 2-Oxobutanoic acid has been converted to (R)- or (S)-2-aminobutanoic acid via highly diastereocontrolled hydrogenation of the corresponding homochiral 3-ethyl-5-phenyl-3,4-dehydromorpholin-2-one derivatives.

Synthesis of α-phenyl proline derivatives via 1,3-dipolar cycloaddition of chiral stabilised azomethine ylids

Abstract The preparation of (3S, 5R)-3,5-diphenylmorpholinone 1 and subsequent diastereoselective 1,3-dipolar cycloaddition of its formaldehyde derived azomethine ylid is described. Removal of the chiral template furnishes α-phenyl proline derivatives.