Palladium-Catalyzed Reactions of Hypophosphorous Compounds with Allenes, Dienes, and Allylic Electrophiles:  Methodology for the Synthesis of Allylic H-Phosphinates

Abstract

Hypophosphorous compounds (MOP(O)H(2), M = H, R(3)NH) effectively participate in metal-catalyzed C-P bond-forming reactions with allenes, dienes, and activated allylic electrophiles under mild conditions. The catalytic system Pd(2)dba(3)/xantphos is crucial to avoid or minimize the competitive reductive transfer-hydrogenation pathway available to hypophosphorous acid derivatives. Further investigation into the allylation mechanism provided access to the analogy allylic acetate-allylic phosphinate, which then led to the development of a Pd-catalyzed rearrangement of preformed allylic phosphinates esters and, ultimately, to a catalytic dehydrative allylation of hypophosphorous acid with allylic alcohols. The reactions disclosed herein constitute efficient synthetic approaches, not only to prepare allylic H-phosphinic acids but also their esters via one-pot tandem processes. In addition, the potential of H-phosphinates as useful synthons for the preparation of other organophosphorus compounds is demonstrated.

Synthesis and Biological Applications of Phosphinates and Derivatives

“…A chemical sequence using isoprenylphosphinate 121 as common precursor to three targeted structures 108-110 has been elaborated. Phosphinic acid precursor 120 was obtained by palladiumcatalyzed hydrophosphinylation from isoprene and hypophosphorous acid [104]. The phosphinate 121 was formed by alkylation of isoprenyl-H-phosphinic acid 120 using N-bromoacetyl aspartic acid dibenzyl ester under silyl-Arbusov conditions.…”

Palladium-catalyzed cross-couplings of allylic carbonates with triarylbismuths as multi-coupling atom-efficient organometallic nucleophiles

“…The metal catalyzed reactions of allylic substrates are useful for a variety of synthetic transformations [1][2][3][4][5][6][7][8][9][10]. The reactivity profile of allylic carbonates differ from other allylic substrates in coupling reactions [11][12][13][14][15][16][17][18][19][20][21][22].…”

Recent Progress in Transition Metal-Catalyzed Addition Reactions of H–P(O) Compounds with Unsaturated Carbon Linkages

“…It may involve initial activation of molecular oxygen to generate highly reactive radical species. Allenes and dienes also react with phosphinic acid or its anilinium salt, typically in the presence of Pd 2 (dba) 3 /xantphos (1 mol%) at 110 C (Scheme 57) [61]. Acetonitrile and DMF are the solvents of choice for phosphinic acid and DMF for the anilinium salt.…”