title: Stereodivergence in amine-catalyzed regioselective [4 + 2] cycloadditions of β-substituted cyclic enones and polyconjugated malononitriles.
abstract: Switchable reaction patterns of β-substituted cyclic enones via amine-based dienamine activation are reported. While γ-regioselective vinylogous Michael addition was observed with alkylidenemalononitriles, a completely different [4 + 2] cycloaddition was obtained with allylidene- or alkynylidenemalononitrile substrates, affording densely substituted bicyclo[2.2.2]octanes or analogous architectures with moderate to excellent diastereo- and enantioselectivity by the catalysis of primary amines from natural quinidine or quinine. Importantly, high diastereodivergence was achieved through unusual hydrogen-bonding interactions of multifunctional primary-amine catalytic systems. Endo cycloadducts were efficiently produced using a combination of 9-amino-9-deoxyepiquinidine and salicylic acid, while exo variants were obtained using 6'-hydroxy-9-amino-9-deoxyepiquinidine. Moreover, we successfully isolated the Michael addition intermediates in some cases, indicating that the above [4 + 2] reaction via dienamine catalysis may proceed by a stepwise Michael-Michael cascade rather than by a concerted Diels-Alder cycloaddition pathway.
authors.affiliation: Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education, West China School of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhou
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000588:Amines; D009570:Nitriles; C000945:dicyanmethane