Copper‐Catalyzed Divergent Trifluoromethylation/Cyclization of Unactivated Alkenes

Abstract

Most of the precedent copper-catalyzedtrifluoromethylation reactions of unactivated alkenes concern terminala lkenes, and these processesa re terminated in elimination, or nucleophilic addition, or semipinacol rearrangement, or C À Hb ondf unctionalization steps.I nt his study,w ed evelop at rifluoromethylation method for bothu nactivated terminal and internala lkenes to enable divergent latestage radical cyclization and achieveh igh molecular complexity.T hese cyclizations are well consistent with Baldwins rule.F urthermore,akinetic isotope effect (KIE) studya nd control reactions were conducted,and aplausible mechanism is proposed.

Hydrogen Atom Transfer‐Mediated Domino Cyclisation Reaction to Access (Spiro)Quinazolinones

“…radicophiles for 1,3-dicarbonyl, [7] trifluoromethyl, [8] phosphoryl, [9] and sulfonyl radicals. [10] Since its discovery in the early 1960s, [11] metal-hydride hydrogen atom transfer (HAT) has become aw idely established methodf or the generation of carbon-centred radicals from alkenes [12] and av ariety of radicophiles have provenc ompatible.…”

Synergistic Effect between Ultrasound Irradiation and Na 2 CO 3 in N ‐Acylation Reaction: Applied for the Synthesis of Novel N ‐Acylcyanamide Derivatives

“…On the other hand, using the characteristic structure of N ‐acylcyanamides in organic synthesis can potentially generate biologically active nitrogen‐containing heterocycles (Scheme )In general, the reactivity N ‐acylcyanamides can be assessed by focusing on radical reactions. For example, these compounds can act as radical precursors for the preparation of quinazolinone moiety . Furthermore, radical synthesis of guanidines and acylguanidines from N ‐acylcyanamides has also been reported .…”

“…Taking advantage of radical reactions of N ‐acylcyanamides, several types of these materials have been constructed. This scaffold typically prepared through the N ‐acylation of cyanamide salts, base‐promoted N ‐acylation of cyanamides, two‐step sequence of cyanation/acylation, or acylation/cyanation of amines . Thus, the N ‐acylation of cyanamides seems to be an efficient and general strategy to prepare these materials.…”

“…For example, these compounds can act as radical precursors for the preparation of quinazolinone moiety. [10][11][12][13][14][15][16][17][18] Furthermore, radical synthesis of guanidines and acylguanidines from N-acylcyanamides has also been reported. [19][20][21] Also, acylcyanamides can be applied for the preparation of benzoxazine compounds.…”

Hydrogen Atom Transfer‐Mediated Cyclisations of Nitriles

“…Encouraged by this result, we next appliedo ur methodology to substrates bearing ac yanamide moiety that could undergo at andem cyclisation with an (hetero)aromatic ring (Scheme 7). To our delight, benzamide 45 underwent the desired transformation in very good yield (70 %) to form spiro-quinazolinone 48.W ea lso pursued challengingt argets 49 and 50,o fd irect relevance [29][30][31] to medicinal chemistry programmes. Nicotinic acid-derived substrate 46 gave 49 as the major product (30%), along with as mall amount of 4-substitutedr egioisomer (5 %); analogously,p yrazole 47 was converted to the complex fused heterocycle 50,a no therwise challengingt arget.…”