Studies on the Synthesis of DMAP Derivatives by Diastereoselective Ugi Reactions

Abstract

Diastereoselective Ugi reactions of DMAP-based aldehydes with α-amino acids and tert-butyl isocyanide were examined. The reactions of 4-(dimethylamino)-2-pyridine-carboxaldehyde with various α-amino acids afforded 2-substituted DMAP derivatives with low diastereoselectivity. On the contrary, reactions with 4-(dimethylamino)-3-pyridine-carboxaldehyde delivered 3-substituted DMAP derivatives with moderate to high diastereoselectivity. The combination of α-amino acid and DMAP-based aldehyde is thus important to achieve high diastereoselectivity. Kinetic resolution of a secondary alcohol using a chiral DMAP derivative obtained through these reactions was also examined.

α-Amino Acids as Synthons in the Ugi-5-Centers-4-Components Reaction: Chemistry and Applications

“…Dimethylaminopyridine (DMAP)-based aldehydes were used with α-amino acids and tert-butyl isocyanide in the Ugi reaction to produce diverse chiral DMAP derivatives [26]. 4-(dimethylamino)-2-pyridine-carboxaldehyde 62 (Scheme 14) afforded products with low diasteroselectivity compared to 4-(dimethylamino)-3-pyridine carboxaldehyde 65 (Scheme 15).…”

Exploitation of the Ugi 5-Center-4-Component Reaction (U-5C-4CR) for the Generation of Diverse Libraries of Polycyclic (Spiro)Compounds

“…Among MCRs, isocyanide (Koopmanschap et al, 2014 ; Giustiniano et al, 2017 )-based ones, and specifically the Ugi reaction (U-4CR) (Dömling and Ugi, 2000 ; Dömling, 2006 ), are by far the most versatile and exploited ones, also because different variants are available. One of these is the so-called Ugi-5-center-4-component reaction (U-5C-4CR) that, employing α (Demharter et al, 1996 ; Ugi et al, 1996 ; Park et al, 1998 ; Kim et al, 2001 ; Zimmer et al, 2001 ; Liu and Dömling, 2009 ; Mandai et al, 2011 ; Mimura et al, 2015 )- or β (Basso et al, 2004 , 2005 , 2010 )-amino acids as bifunctional reagents, generates α,α′-imino dicarboxylic acid derivatives A according to the general mechanism depicted in Scheme 1 .…”

Enantioselective acyl transfer catalysis by a combination of common catalytic motifs and electrostatic interactions

“…According to our continuous efforts for the development of chiral nucleophilic catalysts 17 18 19 to design an efficient and highly enantioselective acyl transfer catalyst that can be prepared in significant quantities without the need for expensive and/or specialized techniques, we envisioned chiral DMAP derivatives that might contain a binaphthyl unit at C4 position of a pyridine ring ( Fig. 2 ).…”

“…1b ) 9 . A similar approach but involving the C3 site of the heterocyclic ring, has been extensively examined 11 12 13 14 15 16 17 18 19 . Nonetheless, reactivity levels were again generally reduced, probably as a result of hampering of proper electron donation by the amino substituent, which raises the energy of the critical pyridinium ion intermediates (cf.…”