Masked 1,3-dipoles

Azomethine ylides are also frequently obtained by ring opening of aziridines, and the analogous carbonyl ylides from oxiranes. These aspects are dealt with in Section 3.03.5.1. A variety of five-membered heterocycles can also function as masked 1,3-dipoles and this aspect is considered in Section 3.03.5.2. 

Use of mesoionic ring systems for the synthesis of five-membered heterocycles with two or more heteroatoms is relatively restricted because of the few readily accessible systems containing two heteroatoms in the 1,3-dipole. They are particularly suited for the unambiguous synthesis of pyrazoles as the azomethine imine is contained as a masked 1,3-dipole in the sydnone system. An attractive feature of their use is that the precursor to the mesoionic system may be used in the presence of the cyclodehydration agent and the dipolarophile, avoiding the necessity for isolating the mesoionic system. 

Alkoxy)alkynylcarbene complexes have been shown to react with nitrones to give dihydroisoxazole derivatives [47]. Masked 1,3-dipoles such as 1,3-thia-zolium-4-olates also react with alkynylcarbene complexes to yield thiophene derivatives. The initial cycloadducts formed in this reaction are not isolated and they evolve by elimination of isocyanate to give the final products [48]. The analogous reaction with munchnones or sydnones as synthetic equivalents of... 

A number of ring systems have been converted into 1,2,4-thiadiazole derivatives. The most common include 5-imino-1,2,4-dithiazolidines, isoxazoles, oxadiazoles, and 5-imino-l,2,3,4-thiatriazolines. In general, a ring-opening reaction is followed by rotation and ring closure, or the heterocyclic ring may act as a masked 1,3-dipole which reacts with a suitable dipolarophile. 

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,... 

The sultam (146) yields the 1,2,4-dithiazolidine (174), thiazolidine (175) or 1,2,4-thiadiazolidine derivatives (176) on heating with an excess of several heterocumulene dipolarophiles (Scheme 29). It is formally acting as a masked 1,3-dipole resulting from elimination of the sulfene moiety (PhCH SOj) <78JOC4951>. 

The thiatriazolines (237), which are obtained from isothiocyanates and alkyl azides are potentially masked 1,3-dipoles (see also Section 4.14.6.7) and react with sulfenes to give the sultams (238), probably through the thiapentalene-like transition state/intermediate (239) (Scheme 45) <78JOC4951>. 

Finally, 5(4Ff)-oxazolones react as masked 1,3-dipoles with nitrileimines, l-nitroso-2-naphthol and [60]fullerene to give 1,2,4-triazoles, naphth[l,2-ci oxazoles and 5 -phenyl-2 7/-pyrrolo[3, 4 l,2][60]fullerene, respectively. 

Reaction kinetics for the interaction of 5-alkyliminothiatriazoles 52 or 58 with heterocumulenes, nitriles, ketones, imines, or other dipolarophiles a=b show that the decomposition of the thiatriazole is bimolecular, and new heterocyclic five-membered rings 71 are formed (Scheme 15). The term masked 1,3-dipolar cycloaddition was used by L abbe and co-workers for this type of reaction <1978JOC4951>, the thioimidate function being the masked 1,3-dipole. The reaction is thought to involve a thiapentalenic intermediate 70 with hypervalent sulfur. The product 71 is itself a masked dipole and often further reactions take place. 

The reaction of acyl isocyanates and a>-cyano alkylazides affords fused products via the postulated thiatriazoline intermediate 75. Then, the masked 1,3-dipole oxathiazoline 76 is generated, and intramolecular reaction takes place, affording the fused 1,2,4-thiadiazole derivatives 77 (Scheme 16) <1993J(P1)27>. 

The very electron-poor picryl isothiocyanate in fact gives very stable thiatriazoline adducts 84 (decomposition temperature >100 °C) with alkyl azides (room temperature, 3 days or at 55 °C, 6-24 h). On the other hand, the reaction of products 84 with alkyl or aryl isocyanates is substantially slower and needs 60 °C (24 h) to take place (Scheme 18). The reaction follows second-order kinetics, and thus is following the masked 1,3-dipole route rather than the thiaziridinimine route <1990JHC1059>. 

The cycloaddition of the mesoionic isoxazole (228) to an iV-(phenylmethylene)benzene sulfonamide provides a versatile entry to 1,4,5-tri- and 1,2,4,5-tetrasubstituted imidazoles which form via eUmination of carbon dioxide and benzenesulfinic acid. The mesoionic (228) are masked 1,3-dipoles ( munchones ) (Equation (70)) <9UCR(S)188,93JCS(P2)i5ii>. 

The interaction of 4-alkyl-5-arylimino-l,2,3,4-thiatriazoline (69) and sulfenes (generated in situ from alkylsulfonyl chlorides and triethylamine82) produces sultams (72), possibly by way of the heteropentalenes (71) these isomerize above 60°C under the influence of acidic catalysts to 73, by a Dimroth rearrangement.77 The sultams (72) are themselves capable of acting as masked 1,3-dipoles, undergoing cycloaddition with heterocumulenes, with elimination of the sulfene moiety. Thus reaction of 72 with phenyl isocyanate produces the 1,2,4-thiadiazolidine (70), also directly accessible from 69 by Path A.83... 

The masked 1,3-dipole, thiatriazole (135), undergoes intramolecular cycloaddition with subsequent elimination of molecular nitrogen, smoothly in ethanol at 75 C to give (136). These reactions were studied in detail with iso thiocyanates, isocyanates, ketenes, and electrophilic nitriles <92T7505>. 

Two types of masked 1,3-dipole, an azomethine ylide and a thiocarbonyl ylide, are present in 1,3,6-triphenylimidazo[l,2-c]thia zole (204). Acetylenic dipolarophiles produced regio- and periselective [3-1-2] cycloadducts (47) (Table 6) by reaction with tbe azometbine ylide 1,3-dipole of (204) <83CL763>. Thus DMAD or benzoylacetylene in dry benzene at room temperature react with (204) to afford (47a R, R = C02Me) and (47b R = H, R = COPb) respectively. Dibenzoylacetylene and metbyl propiolate react with (204) in refluxing benzene to give (47c R, R = COPh) and (47d R = H, R = C02Me) respectively. 

Dauban P, Malik GA (2009) Masked 1,3-dipole revealed from azrridines. Angew Chem Int Ed 48 9026-9029... 

Dauban P, Malik G. A masked 1,3-dipole revealed from aziridines. Angew. Chem. Int. Ed. 2009 48 9026 9029. 

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