Stereoselective cyclopropanation of chiral 5-substituted dihydro-2H-piperazines

The Simmon–Smith cyclopropanation of enantiomerically enriched dehydropiperazines is reported. The reaction is highly stereoselective and allowed us to prepare new, enantiomerically enriched 3-substituted 2,5-diazabicyclo[4.1.0]heptane cores with high diastereomeric purity and a relative anti-configuration, which was assigned by NMR analysis.

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(1S,3S,6R)-tert-Butyl 5-benzyl-3-methyl-2,5-diazabicyclo[4.1.0]heptane-2-carboxylateC18H26N2O2[α]D28=+3.2 (c 1.0, CHCl3)Source of chirality: l-alanineAbsolute configuration: (1S,3S,6R)

(1S,3S,6R)-tert-Butyl 5-benzyl-3-isopropyl-2,5-diazabicyclo[4.1.0]heptane-2-carboxylateC20H30N2O2[α]D28=-24.3 (c 1.0, CHCl3)Source of chirality: l-valineAbsolute configuration: (1S,3S,6R)

(1S,3S,6R)-tert-Butyl 5-benzyl-3-isobutyl-2,5-diazabicyclo[4.1.0]heptane-2-carboxylateC21H32N2O2[α]D28=+2.6 (c 1.0 CHCl3)Source of chirality: l-leucineAbsolute configuration: (1S,3S,6R)

(1S,3S,6R)-tert-Butyl 5-benzyl-3-(4-benzylbenzyl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylateC31H36N2O3[α]D28=-13.2 (c 1.5, CHCl3)Source of chirality: l-tyrosineAbsolute configuration: (1S,3S,6R)

(1S,3S,6R) tert-Butyl 5-benzyl-3-[(benzyloxy)methyl]-2,5-diazabicyclo[4.1.0]heptane-2-carboxylateC25H32N2O3[α]D28=+19.1 (c 1, CHCl3)Source of chirality: l-serineAbsolute configuration: (1S,3S,6R)