Tandem-catalysis-enabled highly chemoselective deoxygenative alkynylation and alkylation of tertiary amides: a versatile entry to functionalized α-substituted amines

Abstract

We report here the highly chemoseive catalytic reductive alkynylation and reductive alkylation of tertiary amides to give propargylamines and α-branched amines, respectively. The method features a tandem iridium (Vaska’s complex)-catalyzed...

Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids

“…In this context, the formation of the C–C bond through catalytic asymmetric reductive alkynylation would not only establish the first asymmetric center but also induce the formation of other stereogenic centers during C–N bond formation (intramolecular reductive amination), constituting a key reaction. Moreover, this methodology highlights the use of alkynes as surrogates for alkyl carbanions 44 , ensuring the necessary chemoselectivity and generality.…”

Dehydrative alkynylation of 3-hydroxyisoindolinones with terminal alkynes for the synthesis of 3-alkynylated 3,3-disubstituted isoindolinones

“…1 Consequently, extensive efforts have been devoted to the development of efficient methods for the construction of organic molecules bearing C(sp)–C(sp 2 ) bonds or C(sp)–C(sp 3 ) bonds. 2 Among strategies for C(sp)–C(sp 3 ) bond formation, 2 e ,3–7 the alkynylation of electrophilic cationic N , O -acetals such as N -acyliminium ions represents one of the key reactions in forming propargylic amines. 2 e ,5 b ,8 However, in these reactions, there are only two examples using readily available terminal alkynes as alkynylation reagents (Scheme 1a).…”

Ir-Catalyzed Chemoselective Reductive Condensation Reactions of Tertiary Amides with Active Methylene Compounds

“…During the past decade, the direct transformation of amides has been attracting increasing attention . Many methods have been developed for the selective reductive transformation of common amides 1 , that is, N- monoacylamines, into diverse classes of N -containing compounds (e.g., 2 and 3 ), which have been experiencing an evolution from using stoichiometric amounts of activating agents or reductants − to catalytic reductive functionalizations (Figure , A). − However, there are very few direct and general C–C bond forming reactions leading to non- N -containing compounds (Figure , B). − This may due to the challenge for the chemoselective cleavage of C–N over C–O bonds of amides . Following the pioneering work of Ghosez and co-workers on the synthesis of cyclic ketones 4 from tert -amides and alkenes (Figure , B1), Hwu (Figure , B2), Charette (Figure , B3), Maulide, and our group ,, have developed few methods for the direct conversion of amides to alcohols 5 and ketones 6 .…”