Benzyne precursors

Another heterocyclic molecule that can serve as a benzyne precursor is benzothiadiazole-1,1-dioxide, which decomposes with elimination of sulfur dioxide and nitrogen. ... 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6- di-melhylamino)julvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), dipkenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopenlane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-5-oxazolone (an important intermediate in amino acid chemistry). 

The l-aminobenzotriazoles are desirable as benzyne precursors. The dianion of N-boc-1-aminobenzotriazole 34 reacts to introduce electrophiles at the 7 position to give 35 in excellent yields <96TL5615>. Pyrrolo[l,2-c][l,2,3]triazoles 37 are formed by trapping... 

The following intermediates in the synthesis of naturally occurring materials have been synthesized by reactions based on a benzyne intermediate. The benzyne precursor is shown. By retrosynthetic analysis identify an appropriate co-reactant that would form the desired compound. 

Obtained both from phenyl[2-(trimethylsilyl)phenyl] iodonium trifluoromethane sulphonate and 2-trimethylsilylphenyltrifluoromethanesulfonate in the presence of tetrabutylammonium fluoride (TBAF). They are good benzyne precursors under mild conditions. 

In refluxing toluene, thiopivalophenones yield both 2H-l-benzothietes and lH-2-benzothiopyrans. Using benzenediazonium-2-carboxylate, as a benzyne precursor, the reaction with 4111 yields a 4H-3,l-benzoxathian-4-one, and selenobenzophenone derivatives18,111 give 4H-3,l-benzooxaselenin-4-ones (see later Scheme 34). 

With benzenediazonium-2-carboxylate or diphenyliodonium-2-carboxylate monohydrate, benzyne precursors, 11 yield 1818 (Scheme 34). 

Finally, it should be pointed out that the diaryne reactions of 1,2,4,5-tetrabromobenzene are stepwise. Thus the procedure described here, but using half the amounts of furan and butyllithium, can be used to prepare 6,7-dibromonaphthalene 1,4-endoxide (mp 115-117°C) in 70% yield.17 This versatile intermediate can then be used as a benzyne precursor, to make unsymmetric adducts 7 13 17 it also can be used as a dienophile.15 18... 

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 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. 

Another heterocyclic molecule that can serve as a benzyne precursor is benzothiadiazole-... 

Reaction of the benzyne precursor (54) with triphenylphosphine arylimides (55) has been shown to give 3-aryl-1,2,3-benzotriazin-4(3/0-ones in poor (< 20%) yield and, while of mechanistic interest, these reactions are of no synthetic significance. Another surprising reaction was reported recently by Moriconi and Shimakawa, who found that... 

Obtained from Eastman Organic Chemicals, b.p. 175-181°. This solvent, in which the benzyne precursor is very sparingly soluble, seemed slightly superior to trimethylene glycol dimethyl ether (b.p. 222°) in which the solubility is considerably higher. o-Dichlorobenzene (b.p. 179°), a still better solvent for the dipolar salt, is less satisfactory than the ether. Diethyl oxalate (b.p. 184°) and N,N-dimethylacetamide (b.p. 195°) are unsatisfactory. 

Special iodonium salts. A range of o-trimethylsilyl-phenyliodonioarenes [111] and heteroarenes [112] as well as some similar Wc-compounds coming from norbornadiene [113] and o-carborane [114] have been obtained from the corresponding bis trimethylsilyl precursors upon reaction with one equivalent of (diacetoxyiodo)benzene. These compounds are useful for their facile in situ conversion into benzyne-type intermediates for benzyne itself the whole procedure is available in Organic Syntheses [115]. A recent improvement involved the synthesis of a new benzyne precursor illustrated in Scheme 38 [116]. 

Benzyne is an important reactive intermediate especially useful for the construction of polycyclic compounds via cycloaddition reactions with various dienes. Several benzyne precursors, including diphenyliodonium-2-carboxylate [ 1 ], have been previously used for the generation of benzyne by thermal decomposition. More recently, several new precursors that generate benzyne quantitatively under very mild conditions have been developed [105 -108]. An efficient benzyne precursor, iodonium triflate 109, can be readily prepared by the reaction of l,2-bis(trimethylsilyl)benzene 108 with [(diacetoxy)iodo]benzene in the presence of trifluoromethanesulfonic acid (Scheme 47) [105]. 

A similar comparative study was performed in case of thiofenchone 100 <2000BCJ155>, which underwent the reaction with two benzyne precursors 96 and 98. This time the benzyne precursor 96 turned out to be more efficient, as the reaction resulted in two isomeric benzothietes 101a and 101b in 72% yield, while the use of compound 98 decreased the yield to 52% (Scheme 16). 

Although there are appreciable differences in the product distributions from the two benzyne precursors, the general trend is about the same and leaves little doubt that both anhydrides react at 690° by forming benzyne. 

When thermolysis was performed in the presence of dienophiles, Diels-Alder products were formed, some of which at the high temperature underwent further transformation for example, tetraphenylcyclopentadienone gave directly 1,2,3,4-tetraphenylnaphthalene (90%) [52]. The use of 2-phenyliodonio benzoate as a source of benzyne was especially suitable with some zwitterionic and mesoionic compounds of low reactivity, which did not react with other benzyne precursors [53]. Another iodonium zwitterion was used for the generation of 2,3-dehydro-naphthalene, which on reaction with tetraphenylcyclopentadienone afforded 1,2,3,4-tetraphenylanthracene. 

This new benzyne precursor combines practical facility in its preparation with relative stability and safety in handling in addition, its conversion into benzyne does not require a strong base or high temperature. Another useful feature of this methodology is that, as with substituted diphenyliodonium 2-carboxylates, only one aryne can be formed from substituted precursors. Indeed, two methyl analogues of 2-trimethylsilyl-diphenyliodonium triflate, in the presence of furan, afforded quantitatively the corresponding adducts high yields of benzyne-diene adducts were also obtained with other 1,3-dienes. 

Phenyl[2-(trimethylsilyl)phenyl]iodonium triflate (226) has emerged as a superior benzyne precursor i.e., admixture of 226 with tetra-n-butylammonium fluoride (TBAF) enables the generation of benzyne in dichloromethane at room temperature (95JCS(CC)983). When organo azides or -nitrones are available in the reaction medium, high yields of the benzotriazoles 227 or benzisoxazolines 228 are obtained (Scheme 62) (98HC205). 

The palladium-catalyzed reaction of allyl chloride 11 with the benzyne precursor 104 to produces phenanthrene derivatives 131 is also known [83]. A plausible mechanism for this intermolecular benzyne-benzyne-alkene insertion reaction is shown in Scheme 38. Initially n-allyl palladium chloride la is formed from Pd(0) and 11. Benzyne 106, which is generated from the reaction of CsF and 104, inserted into la to afford the aryl palladium intermediate 132. A second benzyne insertion into 132 produce 133 and subsequent carbopalladation to the alkene afford the cyclized intermediate 134. f>- Iydride elimination from 134 followed by isomerization gave 9-methylphenanthrene 131. 

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