Optical resolution of trans-bicyclo[2.2.1]heptane-2,3-diamine: chiral recognition in the crystal of its complex with (2R,3R)-O,O′-dibenzoyltartaric acid

A novel asymmetric synthesis of highly enantiomerically enriched norbornane-type diamine derivatives

“…Direct alcoholysis of the intermediate isocyanate by performing the rearrangement in ethanol delivers the corresponding dicarbamate 7, which is converted into the dihydrochloric salt of diamine 8 by reduction and acidic work-up in 71% yield. The absolute configuration of 3Á2HCl was determined by comparison of its sense of optical rotation with that reported in the literature 13 and found to be in accordance with the proposed structure in Scheme 1, which was based on the uniform stereochemical outcome of the asymmetric anhydride opening. Since the value of the optical rotation differed strongly from the published data, the enantiomer ratio of 99:1 was confirmed by HPLC analysis of the corresponding ditosylate 9, using a racemic sample of this compound as reference.…”

“…1 H NMR and 13 NMR spectra were obtained on an Inova 400 spectrometer and were recorded relative to TMS as internal standard. HPLC analysis was performed using a Chiracel OD-H column, 4.6 Â 250 mm, l ¼ 254 nm.…”

“…Only a few years ago, enantiopure 3 was first isolated by resolution of its racemate with O,O 0dibenzoyltartaric acid. 13 Unsatisfyingly, however, this approach afforded the tartaric salt of ent-3 in only 16% yield, based on the racemat. So, a more efficient preparation, which would allow a broader application of this interesting 1,2-diamine, appeared desirable.…”

“…In contrast to the free diamines, 22 the corresponding dihydrochloric salts are stable in air and easy to handle. Since treatment of 3Á2HCl with KOH and distillation under reduced pressure led to the free diamine in only moderate yield, 13 the preferred method was to liberate 3 in situ by addition of an excess of triethylamine before further derivatization. As shown in Scheme 2, this protocol afforded ditosylate 9 as well as salenes 10 and 11 in excellent yields.…”

Bicyclic Conformationally Restricted Diamines

“…The diamine 33a was prepared via N 2 O 4 addition to norbornene 37 followed by reduction (Scheme ), aziridine 38 ring-opening (Scheme ), or double Curtius rearrangement of the corresponding dicarboxylic acid 39 . In the latter approach, enantiopure compounds were obtained using either enantioselective anhydride ring-opening (Scheme ) or resolution with (−)-dibenzoyltartaric acid ((−)-BTA) (Scheme ; the resolution step is not shown) …”