Stephen A. Wald

Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate

Abstract A stereospecific method for the synthesis of enantiopure α-aminoketone from its corresponding α-hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupropion and its biologically active hydroxylated metabolite.

A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine

Abstract A convenient and chromatography-free synthesis for the enantiomers of fluoxetine and norfluoxetine is described. The synthesis relied on the use of the CBS reduction, and Hofman rearrangement to establish the key common intermediate 5 , and enrichment of optical purity of the final product by crystallization as the tartrate salt.

Rigid aminoalcohol backbone as a highly defined chiral template for the preparation of optically active tertiary α-hydroxyl acids

Abstract Constrained aminoalcohol derived-ketoester or amides have provided a new entry for the production of enantiopure acid 1 for (S)-oxybutynin.

REMARKABLY SELECTIVE PALLADIUM-CATALYZED AMINATION PROCESS : RAPID ASSEMBLY OF MULTIAMINO BASED STRUCTURES

Abstract Palladium-catalyzed selective amination by a primary amine in the presence of a secondary amine provided up to >99:1 selectivity with high yields.

Asymmetric synthesis of cetirizine dihydrochloride

Abstract Practical route technology for the preparation of ( S )-cetirizine·2HCl via diastereoselective organometallic addition to N - tert -butanesulfinyl aldimines is disclosed.

PALLADIUM CATALYZED AMINATION OF 2-CHLORO-1,3-AZOLE DERIVATIVES : MILD ENTRY TO POTENT H1- ANTIHISTAMINIC NORASTEMIZOLE

Abstract Palladium-catalyzed selective amination of 4-fluorobenzyl-2-chlorobenzimidazole with 4-aminopiperidine provided a simple solution for the norastemizole synthesis. Pd-catalyzed amination of other 2-chloro-1,3-Azole derivatives are exploited.

Enantio- and diastereoselective synthesis of all four stereoisomers of formoterol

Abstract Enantioselective syntheses of all four stereoisomers of formoterol are accomplished using asymmetric catalytic borane reductions with chiral oxazaborolidines as reducing agents.

Pd-catalyzed aminations of aryl triazolones: Effective synthesis of hydroxyitraconazole enantiomers

Abstract A palladium-catalyzed amination of triazolone 3 by piperazine 2 was used as the key step in an efficient synthesis of highly enantiomerically-pure hydroxyitraconazole isomers. Compound 2 (>99%ee) was prepared by reaction of an achiral phenol precursor with the corresponding dioxolyl tosylate (>99% ee), and 3 was made by alkylation of 6 with 7 (>99%ee).

Conformational toolbox of oxazaborolidine catalysts in the enantioselective reduction of α-bromo-ketone for the synthesis of (R,R,)-formoterol

Abstract Several conformationally constrained oxazaborolidine catalysts have been evaluated in the reduction of ketone 1 . Readily accessible (1R, 2S) 1-amino-2-tetralol (BH) derived oxazaborolidine catalyst ( 6b ) proves to be the most effective and practical catalyst in the reduction of bromo-ketone 1 (96% ee).

Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate

Abstract ( S )-1,4-Benzodioxan-2-carboxypiperazine ( S )- 2 , the key chiral intermediate for the synthesis of ( S )-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase ( Serratia ) followed by amide formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with d -tartaric acid. An efficient process for the conversion of ( S )- 2 to ( S )-doxazosin mesylate was developed (80% yield, 99.9% e.e.).