Browsing by Author "Brackmann, F."

Protected racemic and enantiomerically pure 3,4-(aminomethano) prolines rac-9 and (2S,2'R,3R,4R)-9 have been prepared applying a titanium-mediated reductive cyclopropanation as a key step. Thus, cyclopropanations of NN-dibenzylformamide with titan acyclopropanes generated in situ from racemic or enantiomerically pure tert-butyl N-Boc-3,4-dehydroprolinates rac-8 or (S)-8 proceed diastereoselectively, and furnish the protected racemic and enantiomerically pure diamino acid 9. The latter was incorporated into three tripeptides containing glycyl, alanyl and phenylalanyl moieties.

tert-Butyl N-[1-(hydroxymethyl)cyclopropyl]carbamate (8) was converted into spirocyclopropanated analogues 14-CP and 14-CT of the insecticide Thiacloprid (2) in six simple steps with overall yields of 24% each, along with their regioisomers 13-CP and 13-CT in overall yields of 17 and 15%, respectively. The spirocyclopropanated analogues 27-CP and 27-CT of the insecticide Imidacloprid (1) were prepared from 8 in five steps in an overall yield of 10% each, along with their regioisomers 20-CP and 20-CT in an overall yield of 8 and 7%, respectively. The key step in all preparations was a cocyclization of an appropiately protected (1-aminocyclopropyl)methyl derivative with S,S-dimethyl cyanodithioirninocarbonate (11) or nitroguanidine (22). The structures of several final products and by-products were verified by X-ray crystal structure analyses.

Methyl 1(tert-butoxycarbonylamino)cyclopropanecarboxylate (9) was converted into the spirocyclopropanated fivemembered ring analogue 7a of Iprodione (1) in five steps with an overall yield of 28 %. The spirocyclopropanated fivemembered ring analogue 8a was prepared from tert-butyl N[1-(hydroxymethyl)cyclopropyl]carbamate (10) in five steps with an overall yield of 19 %. En route to the spirocyclopropanated six-membered ring analogues of Iprodione (1), the oxalic acid diamides 5b and 6b could be obtained starting from 9 or 10 in 33 or 19 % yield, respectively. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).

Straightforward syntheses of cyclopropyl analogues of beta-homoornithine and beta-homoglutamic acid are reported. The key step is the titanium-mediated cyclopropanation of 3-benzyloxypropionic acid N,N-dibenzylamide (6), affording N,N-dibenzyl-N-[1(2-benzyloxyethyl)-2-ethenyleyclopropyl]amine (7) in 56% yield as a 2.5:1 mixture of E- and Z-diastereomers. Further transformations of 7 in 9 and 6 simple steps, respectively, furnished 3,6-bis(N-tert-butoxycarbonylamino)-3,4-methanohexanoic acid (13) and 3(N-tert-butoxycarbonylamino)-3,4-methanohexane-1,6-diacid dimethylester (16) as interesting protected beta-(aminocyclopropyl)carboxylic acid building blocks for potentially active small peptide analogues. The structure of the crystalline intermediate tert-butyl (E)-N-{2-[2-(N-tert-butoxycarbonylamino)ethyl-1-(2-hydroxyethyl)]cyclopropyl) carbamate (12) was proved by X-ray diffraction.