Cycloaddition-elimination

Vapor phase pyrolysis of 2-dimethylaminoazirine (168), on the other hand, proceeds in a similar manner at 340 °C to give substituted azadiene (169) in high yield (7SJA4409). Azadiene (169) has been employed in the construction of heterocyclic rings such as pyridines via a [4-1-2] cycloaddition-elimination sequence. 

Several enamines also participate in these cycloaddition reactions. For example, the addition of methyl lithium to benzaldehyde 5 and the sequential introduction of the vinylogous amide and magnesium bromide results in the cycloaddition elimination product chromene 63 (method G, Fig. 4.33).27 The introduction of methyl magnesium bromide to a solution of the benzaldehyde 5 and two equivalents of the morpholine enamine produces the cycloadduct 64 in 70% yield with better than 50 1 diastereoselectivity (method F). Less reactive enamides, such as that used by Ohwada in Fig. 4.4, however, fail to participate in these conditions. 

The reaction of 5(4H)-oxazolones (32) and miinchnones with triphenylvinylphos-phonium bromide (33) provides a mild synthesis of substituted pyrroles (34) (Scheme 11). The cycloaddition-elimination reactions of 5-imino-l,2,4-thiadiazolidin-3-ones with enamines and ester enolates produce 2-iminothiazolidines. " Chiral isomtinchnone dipoles show jr-facial diastereoselectivity with IV-phenyl- or A -methyl-maleimide in refluxing benzene. ... 

As suggested in previous similar investigations, as intermediate have been proposed the non-stable, high-energy species 164, formed in low concentration in a reversible cycloaddition-elimination process of 161 with nitriles. This process either occurs in a concerted manner (pathway A) or involves a four-step sequence with the intermediacy of a bipolar species (pathway B). It has been argued that the reaction does not proceed through a thiatetra-azapentalene intermediate, but instead involves a transition state that resembles structure 164. 

A related cycloaddition/elimination reaction occurs when 5-imino-1,2,4-dithiazolidin-3-ones (300) or -3-thiones (306) are treated with phenylisocyanate to afford 2-phenyl-5-imino-1,2,4-thia-diazolidin-3-ones (307) (Equation (45)) <92JPR685>. 

In contrast, the 5-phenyliminothiatriazoline (323) reacts as a masked 1,3-dipole with a variety of electrophilic nitriles. Tosyl cyanide and ethyl cyanoformate both react with (323) in refluxing chloroform to give initially (324) which then isomerizes to (325) as the reaction proceeds (Scheme 71) <91JHC333>. When the solvent is changed to acetone the reaction with the nitriles proceeds faster due to the formation of the adduct (326) which is capable of undergoing cycloaddition/elimination reactions at 20 °C. Trichloroacetonitrile does not react with (323) in chloroform solution in acetone,... 

Oxathiazolidinimine (180) containing the S—C=N thioamidate grouping can enter the cycloaddition-elimination reaction sequence with iso thiocyanates to give 1,2,4-dithiazolidindiimine (181) which in turn adds-eliminates RNCS to produce diimine (184) which isomerizes into thia-diazolidine (183). Another thiadiazolidine (182) is also formed directly from (180) which apparently... 

Similar facile cycloaddition-elimination reactions are observed when the nitrile group is replaced by an alkyne or alkene group. Thus, thermolysis of thiatriazolines (56) in refluxing benzene for 3 days provided the intramolecular adducts (57) (Equation (5)) <9314439 >. 

R ) (85d). The isomers (86) and (87) were obtained in 47% and 32% yields respectively, establishing the consecutive cycloaddition elimination reactions shown in path (b). 

Oxathiazolidin-3-imine (93) possesses a thioimidate moiety similar to 4-methyl-5-phenyl-imino-l,2,3,4-thiatriazoline (70) and is capable of undergoing cycloaddition-elimination reactions with isothiocyanates to give identical products, however at a much higher rate. Acetone can therefore be used as solvent to catalyze this kind of reaction of thiatriazolines. 

The 1,2,4-thiadiazolidine (369) and the 1,2,4-dithiazolidine (370) are interconvertible in the presence of electrophilic nitriles and give the l,2,4-thiadiazoline-5-ones (371) as products (Scheme 61) (91JOC3268). It is suggested that the reaction goes by a consecutive cycloaddition - elimination mechanism via hypervalent sulfur intermediates in which the nitrile approaches in the plane of the heterocycle. 

Analogous cycloaddition-elimination reactions have been reported for mesoionic imidazolium oxides, which are obtained by the reaction of disubstituted amidines with a-bromoacyl halides (equation 125) (77JOC1639). 

Electron-poor nitriles react with compound 87 and its derivatives to form the 5-amino-l,2,4-thiadiazole derivatives 104 <1985JOC1295>. Therefore, the formation of product 94 (see Scheme 21) may be explained alternatively by the addition of amidonitrile 93 to compound 90. The mechanism of the formation of product 104 was discussed in detail in CHEC-II(1996) <1996CHEC-II(4)691> but most probably the steps involved are (1) reaction of the electrophilic nitrile with the exocyclic nitrogen of compound 87 or its derivatives (2) loss of nitrogen similarly to the previous reactions and formation of an imine 103 (3) masked 1,3-dipolar cycloaddition/elimination reaction of the nitrile to the imine 103. Since the same nitrile is expelled in the elimination step, only 1 equiv of reagent is needed (Scheme 24). 

An original observation was made with the sterically hindered 2,2,4,4-tetramethyl-3-thioxocyclobutanone and arylazides [254]. Dispiro-l,3,4-di-thiazoles were obtained in 67-83% yields. Their formation was explained by a 1,3-dipolar cycloaddition, elimination of N2 and formation of a novel thiocarbonyl ylid, which underwent dipolar cycloaddition with cyclobuta-nethione. The other outcome possible for the ylid was cyclisation to a thia-ziridine and sulfur extrusion to produce the imine, as previously reported. 

Scheme 58 Cl-cycloaddition-elimination three-component s)mthesis of 2-ethoxy substituted P)mdines 107...

Scheme 59 Cl-cycloaddition-elimination three-component synthesis of pyrrolo(2,3- )p5 dines 109, 1,8-naphthyridines 110, and pyrido(2,3-i>)azepines 111...

Scheme 60 Mechanistic rationalization of the Cl-cycloaddition-elimination sequence to anne-lated 2-aminopyridines 109-111...

Alkenyl-4,4-dimethyl-l,3-oxathianes are synthetic equivalents of the highly reactive a,p-unsaturated thioaldehyde system. As such, they react with alkenes in a tandem cationic [4 -l-2] polar cycloaddition - elimination sequence to yield 3,4-dihydro-2//-thiopyrans (Scheme 33) <03T1859>. 

In the case of the attacks of neutral molecules on alkynes, nucleophilic attack is often difficult to distinguish from molecular cycloaddition or electrophilic initiation. Reaction (7) is typical of many which could equally as well be formulated as beginning with a dipolar cycloaddition or an acyclic zwitterion Detailed mechanism of these cycloaddition-elimination reactions remains to be explored... 3 . 

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