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Ligand Bite Governs Enantioselectivity: Electronic and Steric Control in Pd‐Catalyzed Allylic Alkylations by Modular Fenchyl Phosphinites (FENOPs)
Author(s) -
Goldfuss Bernd,
Löschmann Thomas,
Rominger Frank
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200400273
Subject(s) - chemistry , allylic rearrangement , steric effects , aryl , denticity , enantiomer , nucleophile , stereochemistry , ligand (biochemistry) , catalysis , electronic effect , enantioselective synthesis , medicinal chemistry , chelation , tsuji–trost reaction , organic chemistry , crystal structure , receptor , alkyl , biochemistry
Abstract Modular fenchyl phosphinites (FENOPs) containing different aryl units—phenyl ( 1 ), 2‐anisyl ( 2 ), or 2‐pyridyl ( 3 )—are efficiently accessible from (−)‐fenchone. For comparison of the influence of the different aryl units on enantioselectivities and reactivities, these FENOPs were employed in Pd‐catalyzed allylic alkylations. The strongly chelating character of P,N‐bidentate 3 is apparent from X‐ray structures with PdCl 2 ([Pd( 3 )Cl 2 ]), and with allyl–Pd units in ([Pd( 3 )(η 1 ‐allyl)] and [Pd( 3 )(η 3 ‐allyl)]). FENOP3 gives rise to a PdL* catalyst of moderate enantioselectivity (42 % ee , R product). Surprisingly, higher enantioselectivities are found for the hemilabile, monodentate FENOPs 1 (83 % ee , S enantiomer) and 2 (69 % ee , S enantiomer). Only small amounts of 1 or 2 generate selective PdL* catalysts, while complete abolition of enantioselectivity appears with unselective PdL* 2 species with higher FENOP concentrations in the cases of 1 or 2 . Computational transition structure analyses reveal steric and electronic origins of enantioselectivities. The nucleophile is electronically guided trans to phosphorus. endo ‐Allyl arrangements are favored over exo ‐allyl orientations for 1 and 2 due to Pd–π–pyridyl interactions with short “side‐on” Pd‐aryl interactions. More remote “edge‐on” Pd–π–aryl interactions in 3 with Pd‐N(lp) coordination favor endo ‐allyl units slightly more and explain the switch of enantioselectivity from 1 ( S ) and 2 ( S ) to 3 ( R ).