Ylides, nitrile

Trapping of the intermediate acyl nitrile ylide with dimethyl acetylenedicar-boxylate leads to pyrroles in low yields ( 18%) [1250]. Representative examples of the preparation of oxazoles with carbene complexes are listed in Table 4.18. 

The reaction of l-phenyl-3-p-nitrophenylnitriIe ylid (387) to methylenecyclo-propane 4 is the sole reported example of cycloaddition of this dipole type. The only product isolated from the reaction was the pyrrole 390, which arose via 389, 

The only examples dealing with [4 + 1] cycloadditions of alkylidenecyclo-propanes involve the additions of isonitriles to diacylmethylenecyclopropanes. 

The unstable 2-cyclopropylidene-l,3-cycloalkanediones 34a,c,d were trapped in situ by isocyanides 391 to give [4 + 1] cycloadducts under mild reactions conditions to afford 3-spirocyclopropane furans or pyrroles (Table 32) [95]. In the case of 34a, the primary cycloaddition products 392 and 394 decomposed very easily to give the stable pyrrolidindiones 393 and 395, respectively, as a single stereoisomer, upon addition of methanol (entries 1-2). Compounds 34c and 34d gave the expected adducts in moderate to good yields (Table 32, entries 3-7). 

---

The ring opening of 2//-azirines to yield vinylnitrenes on thermolysis, or nitrile ylides on photolysis, also leads to pyrrole formation (B-82MI30301). Some examples proceeding via nitrile ylides are shown in Scheme 92. The consequences of attempts to carry out such reactions in an intramolecular fashion depend not only upon the spatial relationship of the double bond and the nitrile ylide, but also upon the substituents of the azirine moiety since these can determine whether the resulting ylide is linear or bent. The HOMO and second LUMO of a bent nitrile ylide bear a strong resemblance to the HOMO and LUMO of a singlet carbene so that 1,1-cycloadditions occur to carbon-carbon double bonds rather than the 1,3-cycloadditions needed for pyrrole formation. The examples in Scheme 93 provide an indication of the sensitivity of these reactions to structural variations. 

For isoxazoles the first step is the fission of the weak N—O bond to give the diradical (51) which is in equilibrium with the vinylnitrene (52). Recyclization now gives the substituted 2//-azirine (53) which via the carbonyl-stabilized nitrile ylide (54) can give the oxazole (55). In some cases the 2H-azirine, which is formed both photochemically and thermally, has been isolated in other cases it is transformed quickly into the oxazole (79AHC(2.5)U7). 

Frontier molecular orbital theory correctly rationalizes the regioselectivity of most 1,3-dipolar cycloadditions (73JA7287). When nitrile ylides are used as 1,3-dipoles, the dipole... 

The evidence obtained clearly indicates that the above photorearrangements proceed by a mechanism involving a nitrile ylide intermediate since cycloadducts could be isolated when the irradiations were carried out in the presence of trapping agents. Intramolecular cycloaddition of the nitrile ylide followed by a 1,3-sigmatropic hydrogen shift of the initially formed five-membered ring readily accounts for the formation of the final product. 

Nitrile ylides derived from the photolysis of 1-azirines have also been found to undergo a novel intramolecular 1,1-cycloaddition reaction (75JA3862). Irradiation of (65) gave a 1 1 mixture of azabicyclohexenes (67) and (68). On further irradiation (67) was quantitatively isomerized to (68). Photolysis of (65) in the presence of excess dimethyl acetylenedicar-boxylate resulted in the 1,3-dipolar trapping of the normal nitrile ylide. Under these conditions, the formation of azabicyclohexenes (67) and (68) was entirely suppressed. The photoreaction of the closely related methyl-substituted azirine (65b) gave azabicyclohexene (68b) as the primary photoproduct. The formation of the thermodynamically less favored endo isomer, i.e. (68b), corresponds to a complete inversion of stereochemistry about the TT-system in the cycloaddition process. 

A series of 3-imino-2-aryl-l-azetines has been prepared by cycloaddition of nitrile ylides to isocyanides. Thus generation of the nitrile ylides (215) in the presence of cyclohexyl isocyanide gives the 3-cycIohexyIimino-2-aryI-l-azetines (205). Similar 1-azetines are formed by interception of nitrile ylides with a-methylbenzyl isocyanide (72AG(E)47) cf. Section 5.09.4.2.2). 

A novel pyrolytic method of generating nitrile ylides in situ was reported by Burger [44] (equation 45) Such nitrile ylides react with various dipolarophiles alkynes [44] (equation 46), nitriles [45] (equation 47), dimethyl azodicarboxylate [45], aldehydes [45], and nitroso compounds [46]... 

Recently, Burger devised an improved method of carrying out mild, regiospecific cyclizations that involve an intermediate that acts as a synthon for a nitrile ylide of HCN [47 (equation 48). With this methodology, cycloadditions with activated alkenes, alkynes, and azo compounds were earned out [47] (equation 49). All such reported reactions were regiospecific and had the same orientational preference... 

The chalcogene heterocycles have been used as stable precursors for sulfur-said selenium-cantaining hetero-l,3-dienes in cycloaddition reactions 3//-l,2,4-Thiaselenazoles are a convenient source of 4,4-bis(trifluoromethyl)-l-thia-3-aza-buta-1,3-dienes, and 3//-diselenazoles are a convenient source of 4,4-bis(trifluoromethyl)-l-selena-3-azabuta-l,3-dienes as well as bis(tnfluoro-methyl)-substrtuted nitrile ylides [137]... 

Tnfluoromethyl-substUuted 1,3-dipoles of the propargyl-allenyl type and trifluoromethyl-substituted nitrilium betaines. Tnfluoromethyl- [164, 765] and bis(trifluoromethy])-substituted [166, 167] nitrile ylides have been generated by different methods and trapped with various dipolarophiles to yield [3+2] [768] and [3+1] cycloadducts [769], respectively... 

Bis(tnfluoromethyl)-substituted nitrile ylides undergo dimerization reactions in the absence of trapping reagents [143, 168, 170] (equation 38)... 

When 5-ten-butyl-2,2,2-tnmethoxy-3,3 bis(tnfluoromethyl) 2,3 dihydro-1,4,2-oxazaphosphole is pyrolyzed at 700-860 °C and the cycloreversion products are condensed at -196 C, the nitrile ylide formed can be identified by infrared spectroscopy (equation 39) [777]... 

The cyclizations of conjugated nitrile ylides forming substituted oxazoles and thiazoles were computed up to the MP4/6-31H-G level [OOJOC47]. Relative to 23, oxazole-4-carboxylic acid24 is stabilized by about -38.1 kcal/mol (Scheme 18). 

Detailed mechanistic studies101 indicate that benzazepines arc formed by 1,7-electrocyclization of a nitrile ylidc intermediate followed by a [l,5]-sigmatropic hydrogen shift in the initially formed 9a//-2-benzazepine. Similar products, e.g. 9, have been obtained by generating the nitrile ylide 8 from the imidoylchloride, e.g. 7. with potassium /ert-butoxide in tetrahydro-furan.101... 

An elegant procedure for the synthesis of 5//-dibenz[c,e]azepines 14, which is an extension of the procedure outlined at the beginning of this section, has been developed in which the nitrile ylides, generated by the treatment of iV-(2-arylbenzyl)benzimidoyl chlorides 12 with potassium /er/-butoxide, undergo a 1.7-electrocyclization at the adjacent phenyl ring, followed by a hydrogen shift 13 - 14.102... 

Heterocyclic sulphoxides of general structure 185,186 and 187 have been prepared by cycloaddition of diarylsulphines 173b to nitrile oxides 188226, nitrile ylides 189227 and nitrones 190228, respectively (equation 100). 

Iminocarbene complexes of chromium and tungsten are useful isolable synthetic equivalents to nitrile ylides having the advantage that the range of 1,3-dipo-larophiles is not limited to electron-acceptor substrates and can be extended to electronically neutral as well as to electron-rich systems [56] (Scheme 18). 

Oxazole formation can be envisaged as proceeding by three possible pathways 1,3-dipolar cycloaddition of a free ketocarbene to the nitiile (Path A), the formation and subsequent 1,5-cyclisation of a nitrile ylide (Path B) or the formation and subsequent rearrangement of a 2-acyl-2//-azirine (Path C) (Scheme 9). 

Despite the above, there is also considerable evidence to suggest that oxazole formation proceeds via an intermediate nitrile ylide, particularly in the catalysed reactions (see below). Nitrile ylides have been detected in laser flash photolysis studies of diazo compounds in the presence of nitriles, and stable nitrile ylides can be isolated in some cases.<94CRV1091>... 

The role of the rhodium is probably two-fold. Initially due to its Lewis acidity it reversibly forms a complex with the nitrile nitriles are known to complex to the free axial coordination sites in rhodium(II) carboxylates as evidenced by the change of colour upon addition of a nitrile to a solution of rhodium(II) acetate, and by X-ray crystallography. Secondly the metal catalyses the decomposition of the diazocarbonyl compound to give a transient metallocarbene which reacts with the nitrile to give a nitrile ylide intermediate. Whether the nitrile ylide is metal bound or not is unclear. 

The work of Sharp and his many co-workers at Edinburgh cannot be underestimated. In a more recent communication they have extended the scope of his cyclisation of diene-conjugated nitrile ylides to triene homologues <96CC2739>. Thus cyclisation of the triene 21 afforded the cyclopropa[c]isoquinoline 22, which on heating gave a mixture of 23 and 24. The isomeric triene 25 also gave 24 as the sole product (Scheme 4). In this instance the intermediate cyclopropane could not be isolated. 

Reaction of iV-[(benzotriazol-l-yl)methyl]amide 707 with PCI5 gives chloroimine 708, which upon treatment with Bu OK is converted to nitrile ylide 709. Benzyl esters of ot,(3-unsaturated acids used as dipolarophiles trap species 709 to generate pyrroles 712 (Scheme 110) <2002JHC759>. When no trapping agent is added, the N-2 atom of benzotriazole act as a nucleophile, and tricyclic system 711 is formed <2001TL9109>. Addition of benzyl bromide... 

---