Covering: July 1998 to June 2000. Previous review: J. Chem. Soc., Perkin Trans. 1, 2000, 1.

Synthesis of heterocycles by radical cyclisation

Chemistry of α-oxoesters: a powerful tool for the synthesis of heterocycles.

Iron-Mediated Radical Nitro-Cyclization Reaction of 1,6-Dienes

In an attempt to explore the synthetic utility of a ternary asymmetric catalyst comprising La(NO3)3⋅6H2O, amide-based ligand (R)-L1, and D-valine tert-butyl ester H-D-Val-OtBu, we investigated a catalytic, asymmetric amination of functionalized N-nonsubstituted α-alkoxycarbonyl amides using di-tert-butyl azodicarboxylate as an electrophilic aminating reagent. A highly functionalized, cyclic N-nonsubstituted α-alkoxycarbonyl amide delivered the desired amination product in up to 96 % enantiometric excess, with the requisite functionalities of the polar heads of sphingosines with the appropriate stereochemical arrangement. The rapid asymmetric assembly of these functional groups allowed a concise enantioselective synthetic route to sphingosines to be established with a broad flexibility towards derivative synthesis. These studies have culminated in an efficient catalytic enantioselective total synthesis of immunosuppressive fungal metabolites mycestericin F (3 a) and G (3 b).

Catalytic Asymmetric Amination of N-Nonsubstituted α-Alkoxycarbonyl Amides: Concise Enantioselective Synthesis of Mycestericin F and G

N-N bond cleavage in hydrazines is widely used in the preparation of amines and thus occupies a significant place in organic synthesis. In this paper, we report a new method for the reductive cleavage of N-N bonds in hydrazines by commercially available and cheap aqueous titanium(III) trichloride. The reaction proceeds smoothly under a broad pH range from acidic to neutral and basic conditions to afford amines in good yields. This method is compatible with substrates containing functionalities such as C-C double bonds, benzyl-nitrogen bonds, benzyloxy and acyl groups.

Reduction of hydrazines to amines with aqueous solution of titanium(III) trichloride

Glyoxylic acid diphenylhydrazone (2a) and the corresponding O-benzyloxime (2b) are easily esterified in high yield by β-bromo alcohols. The resulting esters undergo radical cyclization to α-(2,2-diphenylhydrazino)- or α-[(phenylmethoxy)amino]lactones on treatment with tributyltin hydride. Esters for radical cyclization were also made using a β-(phenylseleno) alcohol and an enol ether. Several derivatives of glyoxylic acid were evaluated, but none was as effective as 2a or 2b. The imine 28 was prepared by an indirect route; it undergoes radical cyclization with displacement of the nitrogen substituent (28 → 30) so that an α-amino lactone can be generated by acid hydrolysis of the cyclization product.

Sheldon Hiebert

Papers

Preparation of α-(2,2-Diphenylhydrazino)lactones and Related Compounds by Radical Cyclization: Use of Glyoxylic Acid Hydrazone Derivatives

Preparation of α-(2,2-Diphenylhydrazino)lactones and Related Compounds by Radical Cyclization: Use of Glyoxylic Acid Hydrazone Derivatives.