Chiral phenylselenyl derivatives of pyrrolidine and Cinchona alkaloids: nitrogen–selenium donating ligands in palladium-catalyzed asymmetric allylic alkylation

Enantiomeric pyrrolidine alcohols and Cinchona alkaloids reacted with PhSeCN/Bu3P in toluene at 0–25 °C to give the corresponding phenyl selenides with complete inversion of configuration at the substitution centers. Thus, the chiral selenoethers obtained were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. When chiral selenium pyrrolidine derivatives were applied, the enantioselectivity observed was improved versus the respective sulfur pyrrolidine derivatives up to over 98% ee. The results suggest that the pyrrolidine selenoethers served as the effective N(sp3), Se-donating chiral ligands. The selenoethers obtained from Cinchona alkaloids also gave the allylic alkylation product with a higher ee over those for the corresponding thioethers. The results are in agreement with nucleophilic attack directed at the allylic carbon located trans to the chalcogen atom in the intermediate η3-allylpalladium complex.

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(1S,3R,4S,8S,9S)-6′-Methoxy-9-phenylselenylcinchonineC26H28N2OSe[α]D = −46.7 (c 1.20, CH2Cl2)Ee >95%Source of chirality: SN2 substitution on natural quinine

(1S,3R,4S,8S,9S)-10,11-Dihydro-6′-methoxy-9-phenylselenylcinchonineC26H30N2OSe[α]D =−73.3 (c 1.80, CH2Cl2)Ee >95%Source of chirality: SN2 substitution on natural dihydroquinine

(1S,3R,4S,8R,9R)-9-PhenylselenylcinchonineC25H26N2Se[α]D = +69.1 (c 0.98, CH2Cl2)Ee >95%Source of chirality: SN2 substitution on natural cinchonine

(1S,3R,4S,8R,9R)-10,11-Dihydro-6′-methoxy-9-phenylselenylcinchonineC26H30N2OSe[α]D = +160.4 (c 0.96, CH2Cl2)Ee >98%Source of chirality: SN2 substitution on natural dihydroquinidine

(R)-(+)-1-Benzyl-3-2-phenylselenyl pyrrolidineC17H19NSe[α]D = +17.6 (c 0.82, CH2Cl2)Ee >95%Source of chirality: SN2 reaction of (−)-(S)-3-hydroxypyrrolidineAbsolute configuration: 3R (determined by chemical correlation)

(−)-(S)-1-Benzyl-2-(phenylselenylmethyl)pyrrolidineC18H21NSe[α]D = −70.2 (c 0.94, CH2Cl2)Ee >95%Source of chirality: transformation of (−)-(S)-benzyl-2-pyrrolidinemethanol

(S)-(+)-(2-Chloro-benzylidene)-(2-methyl-1-phenylselenyl-propyl)-amineC26H30N2OSe[α]D = +119.8 (c 1.06, CH2Cl3)Ee >98%Source of chirality: transformation of l-valinol