Asymmetric ortho-lithiation of 1, n-dioxa[ n]paracyclophane derivatives for the generation of planar chirality

• Published in: Tetrahedron Vol. 68; no. 5; pp. 1407 - 1416
• Main Authors: Kanda, Kazumasa, Hamanaka, Risa, Endo, Kohei, Shibata, Takanori
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 04.02.2012; Elsevier
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Chemistry, Organic; Enantioselective; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Organic chemistry; ortho-Lithiation; Paracyclophane; Physical Sciences; Planar chirality; Preparations and properties; Science & Technology; ortho-Lithiation; Paracyclophane; Enantioselective; Planar chirality; N-BOC PYRROLIDINE; MIXED DIMER; LITHIUM-AMIDE; GAS-CHROMATOGRAPHY; (+)-SPARTEINE SURROGATE; MESO-EPOXIDES; BRIDGED NADH MODELS; COMPUTER-SIMULATION; CATALYTIC ENANTIOSELECTIVE DEPROTONATION; PARACYCLOPHANES; Enantioselectivity; Nitrogen heterocycle; Stepwise mechanism; Chiral compound; Sparteine; Oxygen heterocycle; Asymmetric induction; Butyllithium; Macrocycle; Planar molecule; Alkaloid; Lithiation; Asymmetric synthesis; Chirality; Enantiomeric excess; Cyclophane; Electrophile
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.12.031

The asymmetric induction of planar chirality in 1, n-dioxa[ n]paracyclophane derivatives via asymmetric ortho-lithiation is described. Enantioselective ortho-lithiation of unflippable 1, n-dioxa[ n]paracyclophanes ( n≤11) using sec-BuLi-(−)-sparteine at −78 °C and subsequent treatment with electrophiles gave the corresponding planar-chiral monosubstituted paracyclophanes with excellent ee. Further lithiation of these compounds and treatment with electrophiles gave planar-chiral paracyclophanes with two different substituents. Dilithiation of unflippable 1, n-dioxa[ n]paracyclophanes gave the corresponding C 2-symmetrical disubstituted products with almost perfect ee. In the case of flippable 1, n-dioxa[ n]paracyclophanes ( n≥12), a stepwise reaction was required for the highly enantioselective formation of disubstituted products. [Display omitted]