Modular synthesis of cyclic cis- and trans-1,2-diamine derivatives

Abstract

Structurally diverse carbocycles with two vicinal nitrogen-substituents were prepared in expedient three-component reactions from simple amines, aldehydes, and nitroalkenes. trans,trans-6-Nitrocyclohex-2-enyl amines were obtained in a one-pot domino reaction involving condensation, tautomerisation, conjugate addition, and nitro-Mannich cyclisation. Upon employment of less nucleophilic carboxamides, a concerted Diels-Alder cycloaddition mechanism operated to give the corresponding cis,trans-nitrocyclohexenyl amides. Both types of substituted carbocycles offer ample opportunities for chemical manipulations at the core and periphery. Ring oxidation with MnO2 affords substituted nitroarenes. Reduction with Zn/HCl provides access to various trans- and cis-diaminocyclohexenes, respectively, in a straight-forward manner. With enantiopure secondary amines, a two-step synthesis of chiral nitrocyclohexadienes was developed (82-94% ee).

1,3-Cyclohexadien-1-Als: Synthesis, Reactivity and Bioactivities

“…In this sense, even when cross-condensation is performed, the autocondensation reaction should be considered as a possible background reaction. In the case of the use of citral, there is frequently the presence of the citral homodimer among the reaction products [57,58], as well as in organocatalyzed cycloaddition in multicomponent reactions [59]. The first use of proline as a catalyst begins with its application in the biomimetic cyclization of citral, synthesizing unsaturated aldehydes (Scheme 29) [54,55].…”

“…In this sense, even when cross-condensation is performed, the autocondensation reaction should be considered as a possible background reaction. In the case of the use of citral, there is frequently the presence of the citral homodimer among the reaction products [57,58], as well as in organocatalyzed cycloaddition in multicomponent reactions [59]. Among the different organocatalysts, the aminocatalysts proline, MacMillan's 138 or 139, and Hayashi-Jorgensen's 137 [60] catalysts can promote Michael addition by iminium salt formation with the acceptor enal.…”

Diastereoselective multicomponent Amine-Aldehyde-Dienophile (AAD) process for the synthesis of polysubstituted cyclohex-2-enylamines

“…13 C NMR δ: 23.3 (=CCH 3 ), 29.7 (=CCH 2 ), 39.1, 41.4 (2xCHC=O), 50.7 (NCH 2 Ph), 53.5 (NCHCH=), 126. 6,128.9,129.0,129.1,129.2,129.3,130.3,131.4,139.7 (ArC,C=C), 177.2, 177.9 (2xC=O). MS (EI) m/z: 346 (M + , 7%), 345 (26), 255 (32), 241 12 4.2.6.…”

“…4.2.10. (3aS,4R,7aS)-2-Phenyl-4-{[(R)-1-phenylethyl]amino}-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H) 6,127.1,127.3,127.7,128.8,128.9,129.3,131.8 (ArC,C=C),177.5,178.9 (2xC=O). MS (EI) m/z: 346 (M + , <1%), 331 14, 173 (43), 120 (100), 106 27 1702,1498,1380,1242,1176,1045,749, 692 cm -1 .…”

“…Few works have been reported using a multicomponent Amine-Aldehyde-Dienophile (AAD) reaction to obtain a cyclohex-2-en-1-amine skeleton 4. Thus, in 2014, Weber and co-workers 6 performed the AAD…”