211. Scope and Limitations of the Reductive Coupling of Aromatic Aldimine Derivatives with Formation of 1,2-Diarylethylenediamine Units, Using Low-Valent Titanium Reagents

Article abstract of DOI:10.1002/hlca.19880710818

Besides the adducts from lithium amides to aromatic aldehydes, iminium salts, aminals, and N-silylimines of aromatic aldehydes are coupled by the black suspension obtained from TiCl4 and Mg turnings in tetrahydrofuran (THF).The 1,2-diarylethylenediamines with tertiary and primary amino groups thus obtained are formed with no or only moderate diastereoselectivity (products 4a-d (Scheme 2) and 5a-e (Scheme 3), respectively); the amine component may contain a strained ring or additional heteroatoms as in azetidin, bis(2-metoxyethyl)amine piperazine, morpholine, and thiomorpholine (products 6a-e; Table 1).By an in-situ procedure, ethylenediamines and propane-1,3-diamines with two secondary amino groups are cyclized with aromatic aldehydes to give exclusively trans-diaryl-substituted piperazine and perhydro-1,4-diazepine derivatives (products 7a-f; Table 2).Enantiomerically pure monocyclic trans,cis-5-alkyl-2,3-diaryl-piperazines and diazabicyclo<4.3.0>nonanes and -<4.4.0>decanes are obtained by employing suitable diamines prepared from the amino acids (S)-alanine, (S)-phenylalanine, (S)-proline, and from (S,S)- or (R,R)-cyclohexane-1,2-diamine, respectively (products 11a-i, 7e; Table 4).The configurations of all products are derived from the high-field NMR spectra, some of which are discussed in detail (Figs. 1 and 2, Tables 3 and 5); all new compounds are fully characterized by their physical data.Depending upon the structure of the components employed, the yields of purified products range from as low as 7percent to essentially quantitative.