Mono- and disubstituted N,N-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 (10 d) 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 (15 a), N-Boc-pyrroline (15 d; 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 10 a and 10 d to yield the fully deprotected 10 e (93 %) and mono-Boc-protected 10 f (98 %), respectively. The latter are interesting templates for combinatorial syntheses of libraries of small molecules with a well defined distance of 4.3 A between two nitrogen atoms.
de Meijere
Armin
A
Institut für Organische Chemie, Georg-August-Universität Göttingen, Tammannstrasse 2, Germany. armin.demeijere@chemie.uni-goettingen.de
Williams
Craig M
CM
Kourdioukov
Alexandre
A
Sviridov
Sergei V
SV
Chaplinski
Vladimir
V
Kordes
Markus
M
Savchenko
Andrei I
AI
Stratmann
Christian
C
Noltemeyer
Mathias
M
D000475:Alkenes / Q000737:chemistry*; D005559:Formamides / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D011437:Propylamines / Q000138:chemical synthesis*; D014025:Titanium / Q000737:chemistry*
D000475:Alkenes; D005559:Formamides; D008024:Ligands; D011437:Propylamines; D014025:Titanium