Unexpected titanium shifts during cyclopropanation of N,N-dibenzylformamide with ligand-exchanged titanium-alkadiene complexes

A number of readily available dienes and a triene were applied to exchange the alkene ligand on the in situ generated titanium-alkene complexes which react with N,N-dialkylcarboxamides to give N,N-dialkylcyclopropylamines. The ligand-exchanged intermediates were found to give the most highly substituted alkenylcyclopropylamines (abnormal products) in good yields (47-64%), rather than the least substituted alkenylcyclopropylamine (expected products). This has been attributed to an unforeseen and unprecedented titanium migration along the ligand. (C) 1998 Elsevier Science Ltd. All rights reserved

Mono- and disubstituted Nu,Nu-dialkylcyclopropylamines from dialkylformamides via ligand-exchanged titanium-alkene complexes

Dibenzylformamide was treated with cyclohexylmagnesium bromide in the presence of either titanium tetraisopropoxide or methyltitanium triisopropoxide and a variety of cyclic and acyclic alkenes and alkadienes to give new mono- and disubstituted as well as bicyclic dialkylcyclopropylamines (Tables 1-3) in yields ranging from 18 to 90 % (in most cases around 55%). 3-Benzyl-6-(N,N'-dibenzylamino)-3-azabicyclo[3.1.0]hexane (10 a) and the orthogonally bisprotected 3-tert-butoxycarbonyl-6-(N,N-dibenzyl)-3-azabicyclo[3.1.0]hexane (10d) as well as the analogous 6-(N,N-dibenzylamino)bicyclo[3.1.0]hexane (12) were obtained as pure exo diastereomers in particularly high yields (87, 90, and 88 %, respectively) from N-benzylpyrroline (15a), N-Boc-pyrroline (15d; Boc=tert-butyloxycarbonyl) and cyclopentene (19). 1,3-Butadiene (52) and substituted 1,3-butadienes were also aminocyclopropanated quite well to give 2-ethenylcyclopropylamines in good yields (51-64%). Except for alkenyl- and aryl-substituted compounds, N,N-dibenzylcyclopropylamines can be debenzylated by catalytic hydrogenation to the primary cyclopropylamines as demonstrated for 10a and 10d to yield the fully deprotected 10c (93%) and mono-Boc-protected 10f (98%), respectively. The latter are interesting templates for combinatorial syntheses of libraries of small molecules with a well defined distance of 4.3 Angstrom between two nitrogen atoms

Intramolecular titanium-mediated aminocyclopropanation of terminal alkenes: Easy access to various substituted azabicyclo[n.1.0]alkanes

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