Catalytic asymmetric synthesis of α- and β-amino phosphonic acid derivatives

Abstract

Catalytic asymmetric reactions provide one of the most powerful and economical synthetic approaches to a variety of enantiomerically enriched compounds. As being analogues of the corresponding alpha- and beta-amino acids, optically active alpha- and beta-amino phosphonic acid derivatives have found widespread use in medicinal chemistry and the pharmaceutical sciences. Using catalytic amounts of chiral materials, asymmetric synthesis of enantiomerically enriched alpha- and beta-amino phosphonates has been a subject of growing interest. This tutorial review contains a compilation of the catalytic asymmetric synthetic methods developed to date and highlights their utility for obtaining these target compounds.

Enantioselective conjugate addition of dialkyl phosphites to nitroalkenes

“…2 Although numerous methods are available in the literature for the synthesis of β-nitro/aminophosphonates, [2][3] there are only handful of approaches for the asymmetric synthesis of such compounds. [3][4] This is despite the fact that introduction of chirality in the flexible aminophosphonic acid chain is likely to enhance its diverse and potent biological properties. The early asymmetric approaches relied primarily on substrate controlled diastereoselective additions.…”

“…14 However, Lewis acids generated by combinations of cinchonine L1 and (S)-BINOL L4 with Ti(O i Pr) 4 , provided only poor results (Table 1, entries 6-7).…”

“…12 Yet another property of such P-nucleophiles is the tautomerism that exists between phosphite (T1) and phosphonate (T2) (Scheme 1). 4 It has been reported that T2 is the active nucleophile while T1 is the resting species. …”

Synthesis of Tröger’s base bis(α-aminophosphonate) derivatives

“…3,4 The other approach is Pudovik reaction where the imines are reacted with dialkylphosphites in the presence of a base or Lewis acid catalyst. 5 Literature is littered with plenty of information on the diverse catalysts 6,8 that accomplish these protocols as well as novel green protocols based on microwave, 9 ultrasound, 10 use of ionic liquids 11,12 etc.…”

Catalytic Hydrogenation of α‐Iminophosphonates as a Method for the Synthesis of Racemic and Optically Active α‐Aminophosphonates

“…[1] A wide range of possibilities of practical use of a-aminophosphonates has stimulated considerable interest in the development of methods for their synthesis. Much experimental material, which is summarized in the monograph [1] and reviews, [2][3][4][5][6] has been accumulated in this area. Considerable recent attention has been focused on the most straightforward approach to a-aminophosphonates based on the rhodium-and ruthenium-catalyzed hydrogenation (first of all, enantioselective [7][8][9][10][11][12][13][14] ) of the corresponding olefinic precursors, and excellent results have been achieved.…”