Inversion of diastereoselectivity under high pressure conditions: Diels–Alder reactions of 12-N-substituted derivatives of (−)-cytisine with N-phenylmaleimide

Diels–Alder adducts of 12-N-substituted derivatives of (−)-cytisine with N-phenylmaleimide were synthesized. The conditions of effective diastereodifferentiation were found: the thermal Diels–Alder reaction of 12-N-substituted derivatives of (−)-cytisine with N-phenylmaleimide leads to 3aS, 4R, 12aR, 12bS adducts, while under high pressure, adducts with 3aR, 4S, 12aS, 12bR configurations of new asymmetric centers are formed. The effect of high pressure on the diastereoselectivity of Diels–Alder reaction was rationalized by theoretical DFT calculations.

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(3aS,4R,8S,12R,12aR,12bS)-10-Allyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-1,3,5(4H)-trioneC24H25N3O3[α]D20 = +13.0 (c 0.9 CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aS,4R,8S,12R,12aR,12bS)

(3aR,4S,8S,12R,12aS,12bR)-10-Allyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-1,3,5(4H)-trioneC24H25N3O3[α]D20 = −14.2 (c 1.1, CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aR,4S,8S,12R,12aS,12bR)

(3aS,4R,8S,12R,12aR,12bS)-10-Benzyl-2-phenyloctahydro-1H-4,12a-etheno-8,12-ethanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-1,3,5(4H)-trioneC28H27N3O3[α]D20 = +8.0 (c 1.0 CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aS,4R,8S,12R,12aR,12bS)

(3aR,4S,8S,12R,12aS,12bR)-10-Benzyl-2-phenyloctahydro-H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-1,3,5(4H)-trioneC28H27N3O3[α]D20 = −16.0 (c 0.9 CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aR,4S,8S,12R,12aS,12bR)

(3aS,4R,8R,12R,12aR,12bS)-1,3,5-Trioxo-N,2-diphenyldecahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-10(7H)-carboxamideC28H26N4O4[α]D20 = +15.0 (c 1.2, CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aS,4R,8R,12R,12aR,12bS)

(3aR,4S,8R,12R,12aS,12bR)-1,3,5-Trioxo-N,2-diphenyldecahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-10(7H)-carboxamideC28H26N4O4[α]D20 = +5.0 (c 1.0, CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aR,4S,8R,12R,12aS,12bR)

(3aS,4R,8R,12R,12aR,12bS)-N-Allyl-1,3,5-trioxo-2-phenyldecahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-10(7H)-carboxamideC25H26N4O4[α]D20 = +17.0 (c 1.1, CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aS,4R,8R,12R,12aR,12bS)

(3aR,4S,8R,12R,12aS,12bR)-N-Allyl-1,3,5-trioxo-2-phenyldecahydro-1H-4,12a-etheno-8,12-methanopyrrolo[3′,4′:3,4]pyrido[1,2-a][1,5]diazocine-10(7H)-carboxamideC25H26N4O4[α]D20 = −6.0 (c 1.2, CHCl3)Source of chirality: (−)-cytisineAbsolute configuration: (3aR,4S,8R,12R,12aS,12bR)