Alkenes nitrile ylides

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 1,3-dipolar cycloadditions of benzonitrile oxides with tertiary cinnamides yield the 5-phenyl and 4-phenyl regioisomers in a reversal of the expected regioselectiv-ities shown with methyl cinnamate. Calculations have shown that steric factors are responsible for this reversal of regioselectivity." The 1,3-dipolar cycloadditions of benzonitrile oxide with electron-rich and electron-poor dipolarophiles are accelerated by sodium dodecyl sulfate micelles. Phenyl nitrile ylides react with electron-deficient alkenes to produce five-membered -heterocycles where measured rate constants are between 4 x 10 and 7 x 10 lmoP ... 

The highly effective desilylation routes to nonstabihzed azomethine ylides have provided the basis for much of this chemistry. Thus, the reaction of A-(silylmethyl)-thioimidates (30) with AgF in the presence of a range of dipolarophiles (electron-deficient alkenes and alkynes, and aldehydes) led to the isolation of nitrile ylide adducts in generally high yields (20,21). Differences in reactivity and regioselectivity... 

Af-(Silylmethyl)thioimidates (34) also undergo water-induced desilylation leading to the N-protonated azomethine ylides (38). These ylides react with a range of electron-deficient alkenes and alkynes, aldehydes, and ketones followed by elimination of methane thiol to give formal nitrile ylide adducts (e.g., 40) (23,24). The reactivity of these species is rather dependent on the nature of R (e.g., good for R = Ph but less so for R=Et or i-Pr), which may be due to competition from tautomerization to give the A -methylthioimidate (39). 

This work has been extended from aryl and alkyl substituted systems (42) (R = aryl, alkyl) to analogues where R is an amino group, so giving access to synthetic equivalents of the nonstabilized amino nitrile ylides (45). Adducts were obtained in good-to-moderate yield with A-methyhnaleimide (NMMA), DMAD, electron-deficient alkenes and aromatic aldehydes (27,28), and with sulfonylimines and diethyl azodicarboxylate (29). Similarly the A-[(trimethylsilyl)methyl]-thiocarbamates (46) undergo selective S-methylation with methyl triflate and subsequent fluorodesilylation in a one-pot process at room temperature to generate the azomethine ylides 47. 

A similar reaction of 70 leads to an amino nitrile ylide synthon (36,37), which reacts with a range of aromatic and heteoaromatic aldehydes to give the 2-oxazolines (71), but which fails to react with ahphatic aldehydes, simple ketones, or activated alkenes. 

Confirmation was provided by the observation that the species produced by the photolysis of two different carbene sources (88 and 89) in acetonitrile and by photolysis of the azirine 92 all had the same strong absorption band at 390 nm and all reacted with acrylonitrile at the same rate (fc=4.6 x 10 Af s" ). Rate constants were also measured for its reaction with a range of substituted alkenes, methanol and ferf-butanol. Laser flash photolysis work on the photolysis of 9-diazothioxan-threne in acetonitrile also produced a new band attributed the nitrile ylide 87 (47). The first alkyl-substituted example, acetonitrilio methylide (95), was produced in a similar way by the photolysis of diazomethane or diazirine in acetonitrile (20,21). This species showed a strong absorption at 280 nm and was trapped with a variety of electron-deficient olefinic and acetylenic dipolarophiles to give the expected cycloadducts (e.g., 96 and 97) in high yields. When diazomethane was used as the precursor, the reaction was carried out at —40 °C to minimize the rate of its cycloaddition to the dipolarophile. In the reactions with unsymmetrical dipolarophiles such as acrylonitrile, methyl acrylate, or methyl propiolate, the ratio of regioisomers was found to be 1 1. 

Much work has been done since the early 1980s on the detailed investigation of the azirine-nitrile ylide interconversion using pulsed-laser photolysis. Thus the azirines 103 (R =R =Ph, R =H R =Me, R = R =Ph R = p-napthyl, R = Me, R = H), on irradiation in isooctane, gave intense long-hved absorptions (250-400 nm) attributed to the nitrile ylides 104 (44). Quenching studies with electon-deficient alkenes led to the determination of absolute rate constants that were similar to those reported earlier for steady-state trapping experiments. The nitrile ylide-olefin reactions are discussed in more detail in Section 7.3.1. 

Extensive work has been done to determine and understand the factors controlling diastereoselectivity in the cycloaddition of nitrile oxides to alkenes but very little is known about nitrile ylides in this regard. Work on their reactions with alkenes that are geminally disubstituted with electron-withdrawing groups (e.g., 187) has illustrated some of the difficulties in such studies. When the imidoyl chloride-base route was used to generate the nitrile ylides it was found that the products 188 epimerized under the reaction conditions. When the azirine route was used, the reaction was complicated by the photochemical isomerization of the dipolarophiles (96,97). Thus, in both cases, it proved impossible to determine the kinetic product ratio. 

Intramolecular cycloaddition of nitrile ylides to olefinic dipolarophiles linked to the dipole by a three-atom chain leads to pyrazoles fused to five-membered rings. Work on stereoselectivity in such reactions has been carried out using the reactant 266 in which the alkene moiety is linked to the C-terminus via a tether that incorporates an enantiomerically pure (R) stereogenic group (165). Both diastereo-isomers 267 and 268 were isolated and it was found that the reaction showed moderate stereoselectivity favoring 267. 

Some interesting new chemistry has been produced on the well-known 1,5-electrocyclization reaction of alkene-conjugated nitrile ylides but the greatest... 

The UV irradiation of the 4,5-dihydro-1,3,5-oxazaphosph(V)olene 39 leads to a cyclic elimination. Analogously to the thermal [5 + 3 + 2] cyclo elimination, the photochemical reaction generated nitrile ylides reacted with alkynes and alkenes to yield the 2/f-pyrrole 40 and the pyrrol-l-ine 41, respectively (equation 17)71. 

The other path by which nitrile ylides react with tr-bonds occurs only in certain intramolecular cases and has been designated as a 1,1-cycloaddition reaction.87 It occurs when the p-orbitals of the alkenic group have been deliberately constrained to attack perpendicular to the nitrile ylide plane. Houk and Ca-ramella have suggested that the 1,1-cycloaddition reaction is initiated by interaction of the terminal cafb-... 

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