Cu-catalyzed asymmetric conjugate reduction of β-substituted α,β-unsaturated phosphonates: an efficient synthesis of optically active β-stereogenic alkylphosphonates

Cu‐Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

“…Recently, the organocatalyzed Michael addition of α‐substituted nitrophosphonates to nitroolefins13 and trimethylphosphonoacetate to α,β‐unsaturated aldehydes14 has been described. Chiral β‐substituted alkylphosphonates have been prepared by using Rh‐catalyzed asymmetric hydrogenation of the corresponding β‐disubstituted α‐β‐unsaturated phosphonates15 and through a Cu‐catalyzed asymmetric conjugate reduction 16…”

Organosilanes in Metal-Catalyzed, Enantioselective Reductions

“…Hu and Zheng employed the combination Cu­(OAc) 2 ·H 2 O/( R )-SEGPHOS ( R )-L2 )/PMHS/ t- BuOH to successfully achieve β-aryl-α,β-vinyl phosphonates (Scheme ). Two alkyl substituted examples produced promising, although lesser, results (68% yield and 89% ee; 68% yield and 86% ee) …”

“…Two alkyl substituted examples produced promising, although lesser, results (68% yield and 89% ee; 68% yield and 86% ee). 181 Buchwald et al coupled styrenes with pyridines with high enantioselectivity and strong regioselectivity for C−C bond formation at the 4-position (rr average of 22:1 for 1,4:1,2 reduction) (Scheme 229). 182 The initial products formed from the dimethoxymethylsilane reductive dearomatization could be further oxidized to 4-alkylated pyridines or reduced to the corresponding piperidine (Scheme 230).…”

Synthetic methods : Part (ii) Oxidation and reduction methods

“…Elsewhere the Yun group report the use of the same JosiPhos ligand (and analogues) to effect Cu-catalysed conjugate reduction of b,b-diaryl acrylonitriles 253 and applied this methodology to the asymmetric synthesis of tolterodine (Scheme 70). 254 Other reports of Cu-catalysed methods include the Koskinen group's report of conjugate reduction of stereochemically labile a,b-unsaturated amino ketones 255 and Hu, Zheng and co-workers' report 256 of asymmetric conjugate reduction of b-substituted a,b-unsaturated phosphonates (wherein the substrates are regioisomeric to the b,g-unsaturated phosphonates they are able to reduce with a Rh-catalyst; see Scheme 45). Non-copper methods of note include Arseniyadis, Cossy and co-workers' report of enantioselective conjugate reduction of b-azolecontaining a,b-unsaturated aldehydes 257 (catalysed by a homochiral imidazolidinone and proceeding in up to 94% e.e.…”