Unnatural α-amino
acids are invaluable building blocks in
synthetic organic chemistry and could upgrade the function of peptides.
We developed a new mode for catalytic activation of amino acid Schiff
bases, serving as a platform for highly congested unnatural α-amino
acid synthesis. The redox active copper catalyst enabled efficient
cross-coupling to construct contiguous tetrasubstituted carbon centers.
The broad functional group compatibility highlights the mildness of
the present catalysis. Notably, we achieved successive β-functionalization
and oxidation of amino acid Schiff bases to afford dehydroalanine
derivatives bearing tetrasubstituted carbon. A three-component cross-coupling
reaction of an amino acid Schiff base, alkyl bromides, and styrene
derivatives demonstrated the high utility of the present method. The
diastereoselective reaction was also achieved using menthol derivatives
as a chiral auxiliary, delivering enantiomerically enriched α-amino
acid bearing α,β-continuous tetrasubstituted carbon. The
synthesized highly congested unnatural α-amino acid could be
derivatized and incorporated into peptide synthesis.
Controlling the reactive species during the synthesis of complex aliphatic chains containing a quaternary carbon is incredibly difficult. In this paper, we efficiently controlled both radical and cationic species in the presence of a copper catalyst. This radical-polar crossover reaction system enables the three-component coupling of styrenes, alcohols, and α-bromocarbonyl compounds as a tertiary alkyl source at room temperature. Mechanistic studies indicated that the reaction contains both radical and cationic species.
In this work, we established a general protocol to synthesize single α-tert-alkylated acetaldehydes via Cu-catalyzed hydroxyalkylation of enamides in aqueous solutions. The yields of the products were very high and there was excellent functional group compatibility. Our reaction allows easy access to highly functionalized acetaldehydes that can be used to synthesize further useful compounds including spirocycles. The control experiments revealed that this reaction includes hydroxyalkylation processes via radical reactions.
In this paper, we established highly
efficient Cu-catalyzed tandem
tert
-alkylation C–H
cyclization of α-bromocarbonyls
and methacrylamides to produce substituted oxindoles. The maximum
turnover number was up to 48 000 with reasonable yield. Although
the catalyst loadings were very low, the reaction was not involving
radical chain reaction. The resulting oxindoles were able to transform
into aza-multicyclic compound via a reduction.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.