Transition‐Metal‐Free Multicomponent Reactions Involving Arynes, N‐Heterocycles, and Isatins

Abstract

Mix and match: With isoquinoline as the nucleophilic trigger, multicomponent reactions afforded spirooxazino isoquinoline derivatives, proceeding through 1,4-dipolar intermediates. The use of pyridine as a nucleophile furnished indolin-2-one derivatives, with the reaction likely proceeding through a pyridylidene intermediate.

Temporary Intramolecular Generation of Pyridine Carbenes in Metal‐Free Three‐Component CH Bond Functionalisation/Aryl‐Transfer Reactions

“…The results of this computational study provided some strong support for both the formation of the pyridylidene 3 by intramolecular proton shift and its nucleophilic addition to N-methyl-isatin (6 a) to give the intermediate zwitterionic adduct Za triggering the final irreversible phenyl transfer with reasonable activation energy barriers for the transition states TS1-TS4 (Figure 2). In particular, these results ruled out the mechanism proposed by Biju and co-workers for the final SnAr step of the reaction; they proposed a sequential mechanism involving a stabilised negatively charged aryl group intermediate, [17] whereas our results indicate that the SnAr step (Za!7 a) actually proceeds through a concerted mechanism via the transition-state TS4. In this transition-state structure, the carbon atom undergoing the nucleophilic substitution is tetracoordinated and adopts a sp 3 -like hybridisation, as shown by bond lengths and angles measurements as well as natural bond orbital (NBO) analyses (Figure 3, see also the Supporting Information).…”

“…The introduction of a 4-amino group on pyrid-2-ylidenes was predicted to increase their stabilisation, [7c] and expectedly, 4-(dimethylamino)pyridine reacted with benzyne (1) and the isatin derivative 6 f, affording the corresponding product 7 j in 52 % yield. [17] …”

“…The model three-component reaction involved pyridine, the benzyne precursor 4 and the isatin derivative 6 a in refluxing THF with KF/ [18]crown-6, and led to the expected bis-arylation product 3-phenoxy-3-(pyridin-2-yl)indolinone 7 a in 64 % isolated yield. [17] The structure of 7 a was deduced from its NMR spectroscopic data and confirmed by X-ray diffraction techniques. [18] The most striking feature in 7 a is the new carbon-carbon bond created between the 2-carbon atom of pyridine and the ketone carbon atom in 6 a by an unprecedented mode of CÀH bond functionalisation.…”

CuI‐Mediated Bromoalkynylation and Hydroalkynylation Reactions of Unsymmetrical Benzynes: Complementary Modes of Addition

“…[19] Namely, the hydroalkynylation products 25m and 25n were efficiently produced in the presence of CuCl when terminal alkynes derived from estradiol and cinchonidine (see SI for details) were used as the trapping agents. This is especially notable because these molecules contain additional potentially competing reactive moieties that include phenol, [8] alcohol, [18] tertiary amine, [19] ether, [20] alkene, [21] cyclic alkane, [22] and quinoline sites [23] . [24] …”

2,3,4,9-Tetrahydro-9-(3-hydroxy-1,4-dioxo-1H-dihydro-naphthalen-2-yl)-8-methoxy-3,3-dimethyl-1H-xanthen-1-one

“…In particular, the recent aryne-based chemistry has made great advances in synthetic chemistry [3][4][5][6][7][8][9][10][11][12][13][14]. Our laboratory is interested in developing domino reactions using arynes.…”