Highly diastereoselective Morita–Baylis–Hillman chemistry: a remote activation effect in the diastereoface selective synthesis of densely functionalized branched cyclic enones from d-glucose

A highly diastereoselective C-2 alkylation of sugar derived cyclic enone 1 in the presence of diethylaluminium iodide by utilizing Morita–Baylis–Hillman chemistry is reported. While diethylaluminium iodide was found to be a suitable Lewis acid for this transformation, the widely employed TiCl4 was ineffective. A plausible mechanism, which considered the involvement of a Zimmerman–Traxler type of closed transition state and an orthoester intermediate, has been discussed.

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(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((S)-hydroxy(4-nitrophenyl) methyl)-2-oxocyclohex-3-enyl acetateC29H27NO8[α]D28=+207.9 (c 3.0, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((S)-(4-cyanophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC30H27NO6[α]D28=+57.8 (c 0.48, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((S)-hydroxy(2-nitrophenyl) methyl)-2-oxocyclohex-3-enyl acetateC29H27NO8[α]D28=+365.0 (c 0.60, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((R)-(2-fluorophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC29H27FO6[α]D28=+60.1 (c 2.03, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((R)-(2,4-difluorophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC29H26F2O6[α]D28=+53.9 (c 1.21, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((S)-(4-chlorophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC29H27ClO6[α]D28=+189.8 (c 0.28, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((R)-(2,3 dichlorophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC29H26Cl2O6[α]D28=+66.6 (c 2.66, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((R)-(2,4 dichlorophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC29H26Cl2O6[α]D28=+155.4 (c 0.71, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((S)-(2,4-dinitrophenyl)(hydroxy)methyl)-2-oxocyclohex-3-enyl acetateC29H26N2O10[α]D28=+219.5 (c 0.76, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(1S,5S,6R)-5,6-Bis(benzyloxy)-3-((R)-(2,3-dichlorophenyl) (hydroxy)methyl)-2-oxocyclohex-3-enyl 4-nitrobenzoateC34H27Cl2NO8[α]D28=-10.6 (c 0.3, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (1S,5S,6R)

(4S,6S,7R,8R,8aS)-6,7-Bis(benzyloxy)-4-(4-cyanophenyl)-2,2-dimethyl-6,7,8,8a-tetrahydro-4H-benzo[d][1,3]dioxin-8-yl acetateC33H33NO6[α]D28=+109.3 (c 0.38, CHCl3)Source of chirality: α,d-glucopyranosideAbsolute configuration: (4S,6S,7R,8R,8aS)