Benzyne reaction with imines

The formation of anthracene in reactions of 185 and 186 with benzyne, which was unexplained by Wittig et aZ., possibly is due to an alternative reaction of the intermediate zwitterion (202) with another molecule of benzjme or with a benzyne precursor. Benzyne reacted with the isoindole (206) to give the tetramethyltriptycene (208) and, in a separate run using excess of the benzyne precursor, W-benzylcarbazole. The latter product would appear to be made up of the iV-benzyl group from an intermediate anthracen-9,10-imine (207) and two molecules of benzyne. Mass spectral evidence also implicated the adduct 207, and the formation of 208 was attributed to benzyne-induced deamination of 207 to 1,4,9,10-tetramethylanthracene, which was trapped by further addition of benzyne across the 9- and 10-positions. 

Dihydroacridines are formed along with 5,6-diphenyl-5,6-dihydrophenanthridines in the reaction of benzyne with imines such as PhCH NPh, which confirms the intermediacy of henzazetidines (C.W.6. Fishwick, R. C. Gupta and R. C. Storr, J. chem. Soc. Perkin I, 1984, 2827). 

Benzynes and substituted benzynes react with isoindoles to give the 9,10-dihydroanthracene-9,10-imines (92).33 A considerable number of substituted compounds of this type have been prepared.27 Triptycene derivatives (i.e., the benzyne adducts of the anthracene system) have been encountered as unexpected products from the reaction of benzyne with 2-benzyl-1,3,4,7-tetramethylisoindole.114... 

Arynes are novel reaction intermediates that react with dienes or 1,3-dipoles to give the corresponding cycloadducts. Recently, many researchers have reported the reaction of benzyne prepared from 2-(trimethylsilyl)phenyl triflate or benzenedia-zonium carboxylate with imines, aminobenzoate, 2-aminobenzophenones, azides, and diazo compounds, which provides various N-containing cycloadducts, such as acridines, acridones, triazoles, and indazoles. Formally, the reaction proceeds in a [2-1-2], [3-1-2], or [4-1-2] manner. Benzyne is an extremely reactive species because of the presence of a strained triple bond and undergoes polar and pericycHc reactions. The lifetime of benzyne in the gas phase has been estimated to around 20 ns (2 X 10" s) by mass spectroscopic techniques. Some spectroscopic properties of benzyne have been determined by Orville Chapman using matrix isolation techniques (Scheme 7.20). 

AMI studies of the 2 - - 2-cycloaddition of ketenimines with imines show that the reaction involves a stepwise mechanism via an intermediate and two transition states. A computational investigation of the thermal 2 - - 2-cycloaddition between imines and ketiminium cations finds that the reaction takes place via a stepwise mechanism.The reaction of benzyne with Schiff bases, diimines, yields l,4-bis(2-substituted acridin-10-yl)benzene via an initial double 2 - - 2-cycloaddition. 

It should be noted that the 1 1 adducts of benzyne with pyrrylmag-nesium iodide, and A -methyl- and iV-benzylpyrrole were isolated and characterized only as the hydrobromide (113), the methiodide (115), and the picrate of 102, respectively. The low yields of all these derivatives are due in part to further reactions of thenaphthalen-l,4-imines with benzyne (see Section III, F and G). Yields are better where the starting pjnrole has an electron-withdrawing N-substituent. Some analogous naphthalen-l,4-imines expected from 1,2,5-trisubstituted pyrroles apparently rearrange spontaneously to j3-naphthylamine derivatives under the conditions for their formation (see Section III, F). The related adducts 107 and 108 are formed from tetrahalobenzynes and N-methy Ipyrrole. 

With one exception, naphthalen-l,4-imines with a double bond between C-2 and C-3 are not known to dissociate thermally by either possible retro-Diels-Alder pathway (the reverse of reactions described in Section III, A, 1 and 2), and the enthalpy requirements for the formation of a benzyne or an acylic acetylene are doubtless unfavorable. However, the mass spectra of compounds 93-99 reveal one important fragmentation of the molecular ions to be loss of dimethyl acetylene-dicarboxylate, and another fragmentation pathway involves the formation of nitrilium ions MeC=NR and PhC=NR from 93-95 and 96-99, respectively. ... 

The formation of a small amount of naphthalene as a by-product of the reaction of benzyne with iV -methylpyrrole was noted by Wittig and Behnisch. Some related examples have recently been described. The tetrachloronaphthalen-l,4-imine (108) with benz5me gave N-methylcarbazole, which it is tempting to see as arising from the reaction of an intermediate zwitterion (compare 166) with another molecule of benzyne or, more likely, a benzyne precursor. The complementary product, 1,2,3,4-tetrachloronaphthalene, was not identified in this case. 

The reactive zwitterions arising from the nucleophilic attack of imines 479 on the benzyne generated in situ from 2-(trimethylsilyl)phenyl triflate 478 proved to be an appropriate molecular scaffold for the capture of CO2 with sufficient electrophilicity to yield 2-aryl-3,l-benzoxazin+-ones 480 (Equation 53). Both substituents of the C=N bond affected the course of the reaction considerably the best yields were achieved by using imines with electron-rich or neutral aryl groups on the carbon, and benzyl or nonbranched chain alkyl substituents on the nitrogen atom. With substituted derivatives of 478, the unsymmetrically substituted arynes led to regioisomeric products <2006JA9308>. 

Processes based on metallation are also useful for the synthesis of indoles. For example, a series of substituted indoles and earbazoles has been synthesized from 2-fluorophenyl imines. Thus for instance, treatment of the imine 88 with LDA in refluxing THF gave the thienoindole 89. Based on labelling experiments, it was suggested that the reaction is probably proceeding via the benzyne intermediate 90 <03S1661>. 

Naphthalene is formed from the N-nitrosoimine 69 at 45°C via a cheletropic reaction.62 In some instances benzyne induces deamination of naphthalen-l,4-imines, since naphthalene was a by-product of the reaction of benzyne with N-methylpyrrole,63 and the naphthalene ester 79 is produced by reaction of 78 with benzyne.68 An indication of the fate of the extruded nitrogen-containing fragment is provided by the identification of N-methylcarbazole as a product of the reaction of 82 with benzyne. 

N-phenylation. The further reaction of 87 and 88 with benzyne to give 9-aminoanthracene derivatives 91 (cf. the mechanism outlined in Scheme 12) is blocked by the presence of substituents at the bridgehead positions as in 86. Anthracene (9%) is also produced from the reaction of 87 with benzyne,48 and the formation of the tetramethyltriptycene 93 from benzyne and the isoindole 92 is attributed to a similar deamination of an intermediate anthracen-9,10-imine.68 Deamination of 86 and 87 is more conveniently accomplished by treatment with hydrogen peroxide.72... 

Interestingly, the discovery of imine anions as potentially useful synthetic intermediates was made serendipitously by Wittig approximately 30 years ago. Acting upon an earlier discovery that lithium diethylamide may serve as a hydride donor to benzyne, Wittig examined the reaction of lithium diethylamide with benzophenone to ascertain whether the latter might also serve as a hydride acceptor. Surprisingly, the products observed from this reaction were benzhydrol (7) and the p-hydroxy aldimine (8) rather than the expected oxidation product (9). The sequence of reactions depicted in Scheme 2 was then proposed to account for this unexpected transformation. The initially produced aldimine (9) undergoes deprotonation with a second equivalent of lithium diethylamide to provide the imine anion (10),... 

Y. Yamashita, T. Hayashi, M. Masumura, Reactions of substituted pyridinium N-imines with benzyne synthesis of pyrido [1,2-6] indazoles... 

Naphthalene-1,4-imines with bridgehead substituents (327) have been made by cycloaddition of benzyne or tetrachlorobenzyne with the appropriate pyrrole. Photochemical reactions of naphthonitriles have been investigated, with... 

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