Oxidative Divergent Bicyclizations of 1,n‐Enynes through α‐C(sp³)–H Functionalization of Alkyl Nitriles

Abstract

An ew,r adical-mediated, divergentb icyclization of 1,n-enynes by a-C(sp 3 )-H oxidative functionalization of alkyl nitriles is described using the Sc(OTf) 3 andA g 2 Os ystem. Ther eactiona llowst he selectivef unctionalization of one or two C(sp 3 ) À H bonds a to the nitrile group by both oxidants and the substitution effect co-controlled the divergent bicy-clization reactions,a nd offersastep-and atom-economicala ccess to diverse polycycles with broad substrate scope and high selectivity.Scheme 2. Bicyclization of 1,n-enynes with alkyl nitriles. Reaction conditions: 1 (0.2 mmol), 2 (2 mL), Sc(OTf) 3 (10 mol%), Ag 2 O( 2equiv;0 .4 mmol), argon, 120 8 8Ca nd 24 h. The dr value is given in the parenthesis as determined by 1 HNMR analysis of the crude product.Scheme 3. Va riation of other enynes. Reaction conditions: 1 (0.2 mmol), 2 (2 mL), Sc(OTf) 3 (10 mol%), Ag 2 O (2 equiv., 0.4 mmol), argon, 120 8 8Cand 24 h. Scheme4.Control experiments.Scheme5.Possible reaction mechanism.

Visible-Light-Induced Atom Transfer Radical Addition and Cyclization of Perfluoroalkyl Halides with 1,n-Enynes

“…On the basis of the above experimental results and previously reported mechanisms, − a possible mechanism was proposed, as outlined in Scheme . First, the photocatalyst [ fac -Ir­(III)­(ppy) 3 ] is irradiated to the excited state [ fac -Ir­(III)­(ppy) 3 *] under visible light irradiation, which is oxidatively quenched by CF 3 (CF 2 ) 2 CF 2 -I to generate a [ fac -Ir­(IV)­(ppy) 3 ] + complex, a n -C 4 F 9 • radical ( A • ), and an iodine anion.…”

“… − Meanwhile, the introducing halo groups provide good opportunities for further modification of these molecules thus obtained (e.g., by well-established cross-couplings). Remarkably, with the combined efforts from Nevado, Tu, − Li, − Liang, − and other groups, − 1, n -enynes ( n = 6, 7), including benzene-tethered 1,7-enynes and N -tethered 1,6-enynes, have been aroused as versatile starting materials in considerable cyclization cascades, which provide facile accesses to pharmaceutically important heterocyclic motifs. In contrast, the ATRA of fluoroalkyl halides to 1, n -enynes ( n = 6, 7) by a distal addition over more than seven atoms, leading to halofluoroalkytated heterocyclic rings, likely attracted less attention from chemists in the past years.…”

Oxone-Mediated Radical Bicyclization of 1,6-Enynes through Dual α-C(sp3)–H Functionalization of Ketones under Catalyst- and Base-Free Conditions

“…To account for all these observations and the reported literature, ,,− ,− we propose a possible mechanism for the formation of the polycyclic γ-lactams in Scheme . Initially, α-carbonyl radical A is first formed from acetone 2a in the presence of oxone under heating. ,, Subsequently, the addition of radical A across C–C double bond in the 1,6-enyne 1a gives the alkyl radical intermediate B , followed by intramolecular cyclization with C–C triple bond to produce the vinyl radical intermediate C . − The intermediate C undergoes a 1,5-H shift to afford new alkyl radical intermediate D , and then cyclization leads to intermediate E . − Finally, the hydrogen abstraction takes place from solvent to furnish the expected product 3aa . ,− …”

“…Radical bicyclization of 1, n -enynes plays an important role in the synthesis of complex polycyclic hydrocarbons in a one-pot strategy. − In 2015, Tu, Li, and co-workers first reported an unprecedented AgNO 3 -catalyzed spirocyclization of 1,7-enynes with cyclo-1,3-dicarbonyls for the synthesis of spiro-cyclopenta­[ c ]­quinolines . Although dual α-C­(sp 3 )–H functionalization of carbonyls was reported, the process relied on two special substrates (5,5-dimethylcyclohexane-1,3-dione and 1,3-dimethylbarbituric acid), both of them having high reactivity.…”

Radical Annulation for the Synthesis of Cyclopenta[c]chromene Derivatives

“…In 2017, only one reaction of phenol‐linked 1,7‐enyne with acetonitrile (CH 3 CN) was repored by Li′ group, [26b] however, the reaction of malononitrile with phenol‐linked 1,7‐enyne has not been found. Therefore, our radical annulation reaction was initiated by treating 1‐((2‐methylallyl)oxy)‐2‐(phenylethynyl) benzene 1 a and malononitrile 2 a as model substrates to investigate the optimum condition (Table 1).…”