Metal-free, photoredox-catalyzed aromatization-driven deconstructive functionalization of spiro-dihydroquinazolinones with α-CF3 alkenes.

Metal-free, photoredox-catalyzed aromatization-driven deconstructive functionalization of spiro-dihydroquinazolinones with α-CF3 alkenes is presented. The readily available spiro-dihydroquinazolinones reacted efficiently with α-CF3 alkenes during photocatalysis to give the gem-difluoroallylated and the CF3-containing quinazolin-4(3H)-ones in good yields with excellent chemoselectivity. The selectivity depends on the electron effect of substituents in α-CF3 alkenes. A wide range of four-, five-, six-, seven-, eight- and twelve-membered spiro-dihydroquinazolinones were compatible with this transformation. The protocol is also characterized by the mild and redox-neutral reaction conditions, good functional group compatibility and excellent atom economy. Mechanistic studies revealed that the reaction proceeds via a radical pathway.

Aromatization-driven deconstructive functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis.

Aromatization-driven deconstruction and functionalization of spiro dihydroquinazolinones via dual photoredox/nickel catalysis is developed. The aromatization effect was introduced to synergistically drive unstrained cyclic C-C bond cleavage, with the aim of overcoming the ring-size limitation of nitrogen-centered radical induced deconstruction of carbocycles. Herein, we demonstrate the synergistic photoredox/nickel catalyzed deconstructive cross-coupling of spiro dihydroquinazolinones with organic halides. Remarkably, structurally diverse organic halides including aryl, alkenyl, alkynyl, and alkyl bromides were compatible for the coupling. In addition, this protocol is also characterized by its mild and redox-neutral conditions, excellent functional group compatibility, high atom economy, and easy scalability. A telescoped procedure involving condensation and ring-opening/coupling was found to be accessible. This work provides a complementary strategy to the existing radical-mediated C-C bond cleavage of unstrained carbocycles.

Photoredox-catalyzed alkylarylation of activated alkenes via a ring-opening/Truce-Smiles rearrangement cascade.

A photoredox-catalyzed alkylarylation of activated alkenes via a radical C-C bond cleavage/Truce-Smiles rearrangement cascade is developed. The protocol features mild and redox-neutral conditions, broad substrate scope and excellent functional group compatibility, providing a facile and efficient approach to the long-chain distal keto-amides with all-carbon quaternary centers at the alpha position.

Alkoxyl Radical-Mediated Ring Expansion/1,4-Difunctionalization of 1,3-Enynes upon Copper Catalysis.

A redox-neutral copper-catalyzed cascade reaction involving alkoxyl radical-mediated ring expansion/1,4-difunctionalization of 1,3-enynes was developed, offering a straightforward approach to the tetra-substituted allenes with macrolactone, CN, and CF3 functional groups. Remarkably, incorporation of the NH2 group onto the 1,3-enyne moiety enabled further cyclization to give a unique scaffold containing a lactone and an indole moiety.

A cheap metal catalyzed ring expansion/cross-coupling cascade: a new route to functionalized medium-sized and macrolactones.

An efficient alkoxyl radical-triggered ring expansion/cross-coupling cascade was developed under cheap metal catalysis. Through the metal-catalyzed radical relay strategy, a wide range of medium-sized lactones (9-11 membered) and macrolactones (12, 13, 15, 18, and 19-membered) were constructed in moderate to good yields, along with diverse functional groups including CN, N3, SCN, and X groups installed concurrently. Density functional theory (DFT) calculations revealed that reductive elimination of the cycloalkyl-Cu(iii) species is a more favorable reaction pathway for the cross-coupling step. Based on the results of experiments and DFT, a Cu(i)/Cu(ii)/Cu(iii) catalytic cycle is proposed for this tandem reaction.

Regioselective and Diastereoselective Dearomative Multifunctionalization of In-Situ-Activated Azaarenes: An Access to Bridged Azaheterocycles.

Reported herein is an unprecedented multicomponent one-pot dearomative multifunctionalization of commercially available azaarenes through an in situ activation strategy, which not only achieved the first full exploitation of the reactive sites of the azaarenes, but also accomplished the efficient synthesis of bridged hydrogenated pyridines and (iso)quinolines in a highly regioselective and diastereoselective manner. In addition, we could successfully realize the step-controlled dearomative trifunctionalization and bifunctionalization of quinolines.

Regio- and diastereoselective dearomatizations of N-alkyl activated azaarenes: the maximization of the reactive sites.

An unprecedented base-promoted multi-component one-pot dearomatization of N-alkyl activated azaarenes was developed, which enabled the synthesis of complex and diverse bridged cyclic polycycles with multiple stereocenters in a highly regio- and diastereoselective manner. Besides, we realized the step-controlled dearomative bi- and trifunctionalization of quinolinium salts. These transformations not only achieved the maximization of the reaction sites of pyridinium, quinolinium and isoquinolinium salts to enhance structural complexity and diversity, but also opened up a new reaction mode of these N-activated azaarenes. A unique feature of this strategy is the use of easily accessible and bench-stable N-alkyl activated azaarenes to provide maximum reactive sites for dearomative cascade cyclizations. In addition, the salient characteristics including high synthetic efficiency, short reaction time, mild conditions and simple operation made this strategy particularly attractive.