Highly diastereoselective addition of chiral H-phosphonate to tert-butylsulfinyl aldimines: a convenient approach to (R)-α-aminophosphonic acids

Asymmetric synthesis of organophosphorus compounds using H–P reagents derived from chiral alcohols

“…47 In continuation of our interest in the asymmetric synthesis of α-aminophosphonates, we have developed an improved protocol for the highly diastereoselective hydrophosphonylation of imines with (R,R)-TADDOL H-phosphonate (2) based on the use of enantiomerically pure (S)-N-tert-butylsulfinyl imines (14a-d) at room temperature and with the use of K 2 CO 3 as a base (Scheme 5). 48 The desired α-aminophosphonates (15a-d) were obtained in good yields (80-87%) and excellent diastereoselectivities (dr >95 : 5 in the majority of cases); consequently, pure major diastereomers could be easily isolated by simple crystallization. Subsequent removal of the chiral auxiliary Organic & Biomolecular Chemistry Review bound to the phosphorus atom and a tert-butylsulfiny protecting group led to enantiomerically pure (R)-α-aminophosphonic acids (16a-d) in good yields (72-92%).…”

“…A broad substrate scope, mild and simple reaction conditions, high yields and diastereoselectivity and simple isolation of major diastereoisomer can be considered as the main advantages of this protocol (Scheme 5). 48 Vicario et al used (R,R)-TADDOL H-phosphonate (2) for hydrophosphonylation of imine 17 and obtained the corresponding racemic α-aminophosphonate 18 (yield 93%, dr 77 : 23) that after chlorination with an excess of trichloroisocyanuric acid (TCCA) followed by the treatment with an excess of poly-(4-vinylpyridine) (Poly-Py) gave α-ketiminophosphonate 19 (Scheme 6). 49 The latter was subjected to nucleophilic addition of Grignard reagents at −80 °C.…”

Probing the reactivity of H-phosphonate derivatives for the hydrophosphonylation of various alkenes and alkynes under free-radical conditions

“…In this regards, their incorporation into numerous compounds has been extensively studied. 2,3 Thus, a large number of synthetic strategies have been proposed [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] as alternatives to traditional methods, i.e. the Michaelis-Arbuzov [20][21][22][23] or the Michaelis-Becker approach.…”

Sequential Deprotonation–Alkylation of Binaphthyloxy-Substituted Phosphonochalcogenoates: Chiral Tri- and Tetrasubstituted Carbon Centers Adjacent to a Phosphorus Atom

“…Optically active phosphonic acids and their derivatives ( I ) with chiral carbon centers adjacent to the phosphorus atom are not only biologically relevant but also versatile synthetic intermediates toward optically active organophosphorus compounds . Accordingly, several synthetic methods for the formation of I with trisubstituted carbon atoms have been developed in past decades − involving the asymmetric addition of phosphorus anions to unsaturated compounds such as carbonyl compounds and imines (Scheme a, method a), the asymmetric reduction of vinyl phosphonates (Scheme a, method b), the asymmetric addition of carbon nucleophiles to unsaturated carbon atoms adjacent to the phosphorus atom (Scheme a, method c), and the addition of carbanions adjacent to the phosphorus atom to electrophiles with chiral ligands (Scheme a, method d) .…”