Stereoselective total synthesis of (+)-β-conhydrine from d-mannitol

An asymmetric synthesis of the piperidine alkaloid (+)-β-conhydrine has been developed starting from (R)-protected glyceraldehyde as the chiral precursor using Barbier allylation, azide nucleophilic substitution, and ring-closing metathesis as the key steps.

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(1R)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-3-buten-1-olC9H16O3[α]D25=+10.8 (c 0.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,4R)

(1R)-1-[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]-3-butenyl azideC9H15N3O2[α]D25=+5.6 (c 0.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,4S)

tert-Butyl N-{(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-butenyl}carbamateC14H25NO4[α]D25=+29.7 (c 0.51, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,4S)

tert-Butyl N-allyl-N-{(1R)-1-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-butenyl}carbamateC17H29NO4[α]D25=+34.8 (c 0.55, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,4S)

tert-Butyl N-allyl-N-{(1R)-1-[(1S)-1,2-dihydroxyethyl]-3-butenyl}carbamateC14H25NO4[α]D25=+10.3 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,1S)

tert-Butyl N-allyl-N-{(1R)-1-[(2S)oxiran-2-yl]-3-butenyl}carbamateC14H23NO3[α]D25=+7.1 (c 0.8, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2S)

tert-Butyl N-allyl-N-{(1R)-1-[(1R)-1-hydroxypropyl]-3-butenyl}carbamateC15H27NO3[α]D25=+17.2 (c 0.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,1R)

tert-Butyl (2R)-2-[(1R)-1-hydroxypropyl]-1,2,3,6-tetrahydro-1-pyridinecarboxylateC13H23NO3[α]D25=+19.7 (c 0.1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)

tert-Butyl (2R)-2-[(1R)-1-hydroxypropyl]hexahydro-1-pyridinecarboxylateC13H23NO3[α]D25=+15.8 (c 0.3, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)

(1R)-1-[(2R)Hexahydro-2-pyridinyl]propan-1-olC8H17NO[α]D25=+8.1 (c 0.6, EtOH)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)