Peter G. M. Wuts

A cautionary note on the use of p-nitrobenzenesulfonamides as protecting groups

Abstract The cleavage of p -nitrobenzenesulfonamides using thiolate was found to give poor regioselectivity. Cleavage requires addition of thiolate at the sulfonamide carbon, but some addition occurs at the nitro carbon resulting in simple displacement of the nitro group rather than sulfonamide cleavage. The side reaction is most prevalent with cyclic amines and steric effects play only a limited role. This lack of regioselectivity is not observed for o -nitrobenzenesulfonamides.

The oxidation of aldehyde bisulfite adducts to carboxylic acids and their derivatives with dimethylsulfoxide and acetic anhydride

Abstract Bisulfite adducts which are readily formed from aldehydes are conveniently oxidized to carboxylic acids and derivatives by the action of DMSO/Ac 2 O followed by quenching with water, an alcohol or an amine.

Synthesis of (2 R ,3 S )-isobutyl phenylisoserinate, the Taxol ® side chain, from ethyl benzoylacetate

Abstract Reduction of ethyl 2-chloro-3-phenyl-3-oxopropionate with borohydride affords predominately the syn -chlorohydrin. Resolution of this ester with the lipase MAP-10 gives (2 S ,3 R )-2-chloro-3-hydroxypropionic acid which after esterification with MeOH/HCl is converted to the cis -epoxide with potassium carbonate and DMF. Aminolysis of the epoxide with aqueous ammonia results in ring opening and amide formation. The amide is converted to an ester upon treatment with isobutyl alcohol and HCl(g) at 100°C. Neutralization then affords the Taxol ® side chain as the free amine.

Dialkylhydrazides for directed orthometalations

Abstract Dimethylhydrazides are shown to be excellent substrates for the directed orthometalation reaction. The advantage of using the hydrazide is that it is easily removed by treatment with H 5 IO 6 or CuCl 2 to give the carboxylic acid under very mild conditions, in contrast to other amides that generally require harshly acidic conditions to achieve hydrolysis.

A new method for deprotection of benzothiazolesulfonamides using a thiol and base

Abstract Benzothiazolesulfonamides of primary and secondary amines are efficiently cleaved by a nucleophilic aromatic substitution with a thiol and a base such as potassium t-butoxide or diisopropylethyl amine in DMF.

Asymmetric synthesis of (–)-exo-brevicomin. Chirality transfer from a chiral (tetrahy-dropyranyloxyallyl)boronate in the condensation with aldehydes

Chirality transfer from a chiral(γ-tetrahydropyranyloxyally) boronate is employed to secure the asymmetry in the synthesis of(–)-exo-brevicomin.

Development of a practical synthesis of sumanirole

A new synthesis of sumanirole that is being developed to treat Parkinsons disease is described. The basic skeleton is constructed from 8-hydroxyquinoline and elaborated to the key tricylic intermediate 14. Further elaboration affords a 1,2-amino alcohol, which is converted to an aziridine by a new process. Finally, dissolving metal reduction to open the aziridine and protecting group removal affords sumanirole.

Convenient Preparation of Optically Pure 3‐Aryloxy‐pyrrolidines

Abstract Chiral 3‐methanesulfonyl‐1‐Boc‐pyrrolidine and piperidine were reacted with sodium phenolates, resulting in a mixture of displacement and elimination products. Following carbamate deprotection and pH adjustment, the 3‐pyrroline and tetrahydropyridine by‐products resulting from elimination were easily removed through aqueous partitioning and/or concentration. Although the pyrrolidines were formed with a high degree of optical purity, slight racemization was observed for the piperidine case because elevated temperatures were required to effect displacement.