220247-74-5Relevant academic research and scientific papers
Mono- and disubstituted N,N-dialkylcyclopropylamines from dialkylformamides via ligand-exchanged titanium - Alkene complexes
De Meijere, Armin,Williams, Craig M.,Kourdioukov, Alexandre,Sviridov, Sergei V.,Chaplinski, Vladimir,Kordes, Markus,Savchenko, Andrei I.,Stratmann, Christian,Noltemeyer, Mathias
, p. 3789 - 3801 (2002)
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 (10a) 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 10e (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 A between two nitrogen atoms.
Functionalized aminocyclopropanes from functionalized organozinc compounds and N,N-dialkylcarboxamides
Wiedemann, Stefan,Marek, Ilan,De Meijere, Armin
, p. 879 - 882 (2002)
Inter- as well as intramolecular competition experiments have been performed to demonstrate that N,N-dialkylcarboxamides react faster than tert-butyl esters with the titanium intermediates formed from ethylmagnesium bromide and methyltitanium triisopropox
Unexpected titanium shifts during cyclopropanation of N,N- dibenzylformamide with ligand-exchanged titanium-alkadiene complexes
Williams, Craig M.,Chaplinski, Vladimir,Schreiner, Peter R.,De Meijere, Armin
, p. 7695 - 7698 (2007/10/03)
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 intermedia
A New Versatile Reagent for the Synthesis of Cyclopropylamines Including 4-Azaspiro[2.n]alkanes and Bicyclo[n.1.0]alkylamines
Chaplinski, Vladimir,Winsel, Harald,Kordes, Markus,De Meijere, Armin
, p. 111 - 114 (2007/10/03)
The reaction of dialkylcarboxamides 1 with 1 equiv. of methyltriisopropyloxytitanium together with only 1.1 equiv. of a Grignard reagent gives cyclopropylamines 3 in better yields than the previously published method with 2 equiv. of Grignard reagent and 1 equiv. of Ti(OiPr)4. This new protocol can be applied to intramolecular reactions with in situ generation of the Grignard reagent from ω-bromo-N,N-dimethylhexanamide and methyl ω-bromohexanoate yielding the expected 1-dimethylaminocyclo[4.1.0]hexane 15 and the corresponding alcohol 18. Cyclohexylmagnesium bromide or chloride transforms N,N-dibenzylformamide and ethyl acetate to 7-exo-N,N-dibenzylaminonorcarane and 7-exo-hydroxy-7-methylnorcarane. N-Methyl-ε-caprolactam 25b and even the strained N-benzylpropiolactam 25a were converted to the spirocyclopropanated heterocycles 26a,b.
