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. 2013 Oct 6;45(13):1430-1748.

Facile Access to Ring-Fused Aminals via Direct α-Amination of Secondary Amines with ortho-Aminobenzaldehydes. Synthesis of Vasicine, Deoxyvasicine, Deoxyvasicinone, Mackinazolinone and Ruteacarpine

Matthew T Richers  1 , Indubhusan Deb, Alena Yu Platonova, Chen Zhang, Daniel Seidel
Affiliations

Facile Access to Ring-Fused Aminals via Direct α-Amination of Secondary Amines with ortho-Aminobenzaldehydes. Synthesis of Vasicine, Deoxyvasicine, Deoxyvasicinone, Mackinazolinone and Ruteacarpine

Matthew T Richers et al. Synthesis (Stuttg). .

Abstract

Secondary amines undergo redox-neutral reactions with aminobenzaldehydes under conventional and microwave heating to furnish polycyclic aminals via amine α-amination/N-alkylation. This unique α-functionalization reaction proceeds without the involvement of transition metals or other additives. The resulting aminal products are precursors for various quinazolinone alkaloids and their analogues.

Keywords: Aminals; C–H bond functionalization; Friedländer condensation; Quinazolinone alkaloids; Redox Isomerization.

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Figures

Figure 1
Figure 1
Top and side views of the X-ray crystal structures of 9c (left) and 10a (right).
Scheme 1
Scheme 1
Examples of amine α-amination via C–H bond functionalization.
Scheme 2
Scheme 2
Serendipitously discovered redox-neutral formation of aminals.
Scheme 3
Scheme 3
Reactions of pyrrolidine with various ortho-aminobenzaldehydes.
Scheme 4
Scheme 4
Reactions of ortho-aminobenzaldehydes with various cyclic amines.
Scheme 5
Scheme 5
Mechanism of the aminal formation.
Scheme 6
Scheme 6
Optimized microwave conditions for other substrates.
Scheme 7
Scheme 7
Direct comparison of reflux vs. microwave conditions for various amines.
Scheme 8
Scheme 8
Regioselectivity of the aminal formation.
Scheme 9
Scheme 9
Impact of electronic factors on the regioselectivity and yield of the aminal formation.
Scheme 10
Scheme 10
Aminal formation with aminoketones.
Scheme 11
Scheme 11
Formation of aminobenzaldehyde self-condensation products.
Scheme 12
Scheme 12
Decarboxylative formation of aminals.
Scheme 13
Scheme 13
Regioselectivity in the decarboxylative aminal formation.
Scheme 14
Scheme 14
Attempted capture of azomethine ylide intermediates.
Scheme 15
Scheme 15
Attempts to capture azaquinonemethide intermediates.
Scheme 16
Scheme 16
Synthesis of quinazolinone alkaloids and analogues.
See this image and copyright information in PMC

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