Lewis Base-Catalyzed One-Pot Cascade Sequences of O-Alkenyl-Substituted Cyanohydrins: Diastereoselective Synthesis of Multisubstituted Dihydrofurans

Abstract

The first example of the diastereoselective construction of polysubstituted 2,3-dihydrofurans incorporating contiguous quaternary and tertiary carbon centers via a Lewis base-catalyzed one-pot cascade sequence is described. The diversity and complexity of the final products can be efficiently constructed with high diastereoselectivities via this catalytic multistep process under mild reaction conditions.

Organocatalytic Allylic Alkylation of α-(Alkylideneamino)nitriles and Its Application in the Preparation of Multisubstituted 1-Pyrrolines

“…We have demonstrated that allylic substituted α-amino nitriles, readily prepared from a Lewis base-catalyzed allylic alkylation of Morita–Baylis–Hillman (MBH) adducts with α-amino nitriles bearing an α-hydrogen, can serve as versatile scaffolds to prepare a series of nitrogen-containing heterocycles. , In these transformations, N-allylic-substituted α-amino nitriles or C-allylic-substituted α-amino nitriles can undergo Brønsted base- or Lewis base-promoted intramolecular nucleophilic cyclizations to provide azaheterocycles. − In particular, transition metal-free intramolecular carbocyanation and acylcyanation approaches enabled efficient assembly of functionalized isoquinoline, quinoline, pyridine derivatives, and pyrrolo­[2,1- a ]­isoquinoline derivatives incorporating quaternary carbon centers (Scheme a). − As part of our continuous effort to develop efficient metal-free processes for preparing functionalized azaheterocyclic scaffolds, , we envisioned that a Lewis base-catalyzed allylic alkylation of α-(alkylideneamino)­nitrile with an MBH adduct would deliver allylic-substituted α-(alkylideneamino)­nitrile bearing an activated alkene moiety, which may undergo a Lewis base-catalyzed 1,4/1,2-addition tandem sequence to provide a practical approach for accessing multisubstituted 1-pyrrolines incorporating β-quaternary carbon centers in an atom-economic fashion (Scheme b), with the distinct feature that iminyl group serves as an intramolecular tandem addition acceptor. Herein, we report our results.…”

Cyanovinylation of Aldehydes: Organocatalytic Multicomponent Synthesis of Conjugated Cyanomethyl Vinyl Ethers

“…Cyanomethyl vinyl ethers (CMVEs) 1 constitute densely functionalized linear synthetic platforms which have found use as monomeric units in the construction of alkenyl ether-vinyl ester copolymers [ 1 , 2 , 3 , 4 , 5 ], as building blocks in the construction of multi-substituted 2,3-dihydrofurans [ 6 , 7 ] and 2,3-dihydropyrroles [ 7 ], and as convenient platforms for mechanistic investigations in the Claisen rearrangement of allyl vinyl ethers [ 8 , 9 , 10 ] ( Scheme 1 A). They are usually synthesized in a step-wise manner from the corresponding aldehydes through the formation of the O -formyl cyanohydrin intermediate and carbonyl methylenation [ 9 ] ( Scheme 1 B).…”

“…They are usually synthesized in a step-wise manner from the corresponding aldehydes through the formation of the O -formyl cyanohydrin intermediate and carbonyl methylenation [ 9 ] ( Scheme 1 B). When the vinyl moiety is endowed with electron withdrawing groups (e.g., 3 ), the cyanohydrin is directly converted into the conjugated cyanomethyl vinyl ether derivative by the amine-catalyzed Michael addition on the corresponding conjugated alkyne [ 6 , 7 ] ( Scheme 1 B). In both protocols, the corresponding cyanohydrin has to be synthesized and isolated to be used in the following reaction step.…”