Three (-)-fenchyl alcohol derivatives, ¿(1R,2R,4S)-exo-(2-Ar)-1,3, 3-trimethylbicyclo[2.2.1] heptan-2-ol, Ar = o-anisyl (2), 2-N-methylimidazolyl (3), 2-N,N-dimethylbenzylamine (4)¿ were synthesized, characterized by X-ray analyses, and employed as precatalysts in diethyl zinc additions to benzaldehyde. Directions and relative degrees of enantioselectivities are rationalized by QM/MM ONIOM computations of mu-O transition structure models. Enantioselectivities arise from repulsive interactions between "transferring" or "passive" alkyl groups at the zinc centers and the substituents at donor groups or the bicyclo[2.2.1]heptane moieties. These results enable predictions for ligand-tuning to improve catalyst efficiency of fenchone-based ligands in dialkylzinc additions to aldehydes.
Trimethylsilyl substitutions of the fenchyl alcohols [(1R,2R,4S)‐exo‐(2‐Ar)‐1,3,3‐trimethylbicyclo[2.2.1]heptan‐2‐ol, Ar = 2‐methoxyphenyl (1) and Ar = 2‐(dimethylaminomethyl)phenyl (2)] yield the chiral ligands 3 [Ar = 2‐methoxy‐3‐(trimethylsilyl)phenyl] and 4 [Ar = 2‐(dimethylaminomethyl)3‐(trimethylsilyl)phenyl]. Increased reactivities and enantioselectivities in diethylzinc additions to benzaldehyde are obtained from 3 (63% ee R) and 4 (93% ee S), relative to 1 (26% ee S) and 2 (73% ee S). X‐ray crystal structures of 3 and of its methylzinc complex 3‐Zn reveal out‐of‐plane bending of the methoxy groups as major geometrical consequences of the trimethylsilyl substitutions. Analyses of QM/MM ONIOM μ‐O transition‐structure models for 1, 2, 3, and 4 show that trimethylsilyl‐induced distortions of methoxy and of dimethylaminomethyl groups explain the observed increased enantioselectivities.
Chiral, enantiopure aggregates are formed spontaneously by mixing solutions of n-butyllithium with anisyl fenchols. X-ray crystal analyses reveal the structures of these aggregates with different ortho substituents in the anisyl moieties (X), X = H (1-H), SiMe3 (2-H), tBu (3-H) SiMe2(tBu) (4-H) and Me (5-H). While the complex of 1-BuLi shows a 3:1 composition, 2-BuLi, 3-BuLi and 4-BuLi yield 2:2 stoichiometries. The aggregate 5-BuLi crystallizes with a 2:4 composition and hence is a derivative of hexameric n-butyllithium, in which two trans-situated nBuLi molecules are substituted by lithium fencholate moieties. The variety in the synthesized chiral nBuLi aggregates demonstrates the high propensity of anisyl fencholates to chirally modify nBuLi. Variations in the modular ligand structures by alterations of the ortho-substituents (X) enable tunings of compositions and also of enantioselectivities in nBuLi additions to benzaldehyde.
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