An Overview on the N-Heterocyclic Carbene-Catalyzed Aza-Benzoin Condensation Reaction

Abstract

Abstract:The N-heterocyclic carbene(NHCs)-catalyzed aza-benzoin condensation reaction is an efficient, single step strategy which employs easily available substrates, such as aldehydes and imines, to provide α-amino ketones. The multifunctionality and high reactivity of α-amino ketones makes these structures attractive for medicinal chemistry and as precursors of a variety of amine derivatives. The different electrophilic characteristics of aldehydes and imines ensure a high regioselective reaction. Enantiomerically-enriched α-amino ketones have been synthesized through stereoselective couplings promoted by chiral N-heterocyclic carbenes. One-pot domino procedures, including an aza-benzoin step, allow valuable complex molecules to be accessed.

Asymmetric Transfer Hydrogenation: Dynamic Kinetic Resolution of α-Amino Ketones

“…The reduction of a range of substrates 13b – 13l and 14b – 14l and the precursors to 23 – 27 was undertaken (Figure ). The N -Boc-protected ketones were prepared initially, and then the N -Ts-protected ketones were prepared via their deprotection followed by N -tosylation. A representative series of substrates were prepared with electron-donating (OMe) and electron-withdrawing (Cl) substituents at the o -, m- , and p - positions of each aromatic ring Ar 1 /Ar 2 .…”

“…Compounds 12a – 14a (Table ) were prepared via bromination of α-phenylacetophenone, reaction with potassium phthalimide, and then deprotection and addition of the N-protecting group, whereas 15a was prepared through the reaction of an acylimine with benzaldehyde using a thiazolium catalyst (Supporting Information). A series of conditions were tested using catalyst ( R , R )- 2 .…”

NHC-Catalyzed Aza-Benzoin Condensation of N,N′-Dipyridin-2-yl Aminals with Aldehydes

“…For instance, it is found in the antidepressant bupropion , and the vasoconstrictor adrenalone . α-Amino ketones can be accessed from various substrates, ,− including α-amino acids, , alkenes, and ketones. − Imines provide another synthetic starting point toward α-amino ketones. − The NHC-catalyzed aza-benzoin condensation reaction between aldehydes and imines is a convenient synthetic method for α-amino ketones. − However, since imines may be unstable, it is common to form them in situ (Scheme ). − …”

Organocatalytic Name Reactions Enabled by NHCs

“…At the same time, NHC catalysis often enables highly stereoselective synthesis, which is important in the preparation of natural and/or biologically active compounds. Numerous review papers and books summarize the importance of NHC researchers' achievements [1][2][3][4][5][6][7][8][9]. However, it is hard to look for any article mostly emphasizing the role of N-heterocyclic carbene catalysis in the history of organic chemistry.…”