Ruthenium-catalyzed one-pot ring-closing metathesis/syn-dihydroxylation in the synthesis of bicyclic iminosugars

Novel polyhydroxylated derivatives of quinolizidine and decahydropyrido[1,2-a]azepine were prepared starting from a common oxazolidinone. The bicyclic cores were prepared by a ruthenium-catalyzed ring-closing metathesis, followed by re-use of the catalyst in the subsequent syn-dihydroxylation in a one-pot procedure.

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1-{(2S,3S,4S,5R)-3,4,5-Tribenzyloxy-2-[(1R)-1-hydroxyprop-2-en-1-yl]piperidin-1-yl}prop-2-en-1-oneC32H35NO5Source of chirality: chiral pool[α]D23 = +16.1 (c 1, DCM)Absolute configuration: (2S,3S,4S,5R) (1R)

(1R,7R,8S,9S,9aS)-1-Hydroxy-7,8,9-tribenzyloxy-1,6,7,8,9,9a-hexahydro-4H-quinolizin-4-oneC30H31NO5Source of chirality: chiral pool[α]D23 = −111.7 (c 1, DCM)Absolute configuration: (1R,7R,8S,9S,9aS)

(1S,2R,3R,7R,8S,9S,9aR)-1,2,3-Trihydroxy-7,8,9-tribenzyloxyoctahydro-4H-quinolizin-4-oneC30H33NO7Source of chirality: chiral pool[α]D23 = −0.4 (c 1, MeOH)Absolute configuration: (1S,2R,3R,7R,8S,9S,9aR)

1-{(2S,3S,4S,5R)-3,4,5-Trihydroxy-2-[(1R)-1-hydroxyprop-2-en-1-yl]piperidin-1-yl}but-3-en-1-oneC33H37NO5Source of chirality: chiral pool[α]D23 = +0.9 (c 1, DCM)Absolute configuration: (2S,3S,4S,5R) (1R)

(1S,2S,3R,10R,10aS)-1,2,3-Tribenzyloxy-10-hydroxy-1,3,4,7,10,10a-hexahydropyrido[1,2-a]azepin-6(2H)-oneC31H33NO5Source of chirality: chiral pool[α]D23 = −45.7 (c 1, DCM)Absolute configuration: (1S,2S,3R,10R,10aS)

(1S,2S,3R,10S,10aS)-1,2,3-Tribenzyloxy-8,9,10-trihydroxy-octahydropyrido[1,2-a]azepin-6(2H)-oneC31H35NO7Source of chirality: chiral pool[α]D23 = −18.1 (c 1, MeOH)Absolute configuration: (1S,2S,3R,10S,10aS)

(1R)-1-[(2R,3S,4S,5R)-1-Acryloyl-3,4,5-tribenzyloxypiperidin-2-yl]prop-2-en-1-yl acetateC34H37NO6Source of chirality: chiral pool[α]D23 = −6.4 (c 1, DCM)Absolute configuration: (1R)(2R,3S,4S,5R)

(1S,7R,8S,9S,9aR)-2,3-Dihydroxy-7,8,9-tribenzyloxy-4-oxooctahydro-2H-quinolizin-1-yl acetateC32H35NO8Source of chirality: chiral pool[α]D23 = +1.0 (c 1, DCM)Absolute configuration: (1S,7R,8S,9S,9aR)

(1R)-1-[(2R,3S,4S,5R)-1-(But-3-enoyl)-3,4,5-tribenzyloxypiperidin-2-yl]prop-2-en-1-yl acetateC35H39NO6Source of chirality: chiral pool[α]D23 = −6.3 (c 1, DCM)Absolute configuration: (1R)(2R,3S,4S,5R)

(1S,2S,3R,10S,10aR)-1,2,3-Tribenzyloxy-8,9-dihydroxy-6-oxodecahydropyrido[1,2-a]azepin-10-yl acetateC33H37NO8Source of chirality: chiral pool[α]D23 = −11.3 (c 1, DCM)Absolute configuration: (1S,2S,3R,10S,10aR)