Heterocumulenes synthesis

Stable zirconate complexes of type 31 have also been described by the [3 + 2] cycloaddition of a-phosphino zirconaindene with alkyne derivatives, and the method has been extended to the synthesis of zirconium complexes from various heterocumulenes X=C=Y (X,Y=0,S,CyN) (Scheme 15) [69,70]. 

Carbon monoxide carbo-mers [5-7], i.e., monoxides of linear odd carbon chains longer than one C 0 n = 3, 5, 7, 9...), are highly reactive molecules suggested as potential constituents of interstellar and circumstellar gas clouds. Considerations based on MO theory and quantum chemical calculations indicate that, similar to pure odd carbon chains, all these heterocumulenes are singlet carbenes in the ground state [93]. Since its matrix isolation in 1971 [94] and its synthesis in gas phase in 1983 [95], the simplest member of this family, i.e., tricarbon monoxide C3O, has been extensively studied both experimentally and theoretically [96-102], and its interstellar presence fully confirmed [103]. In particular, on the basis of... 

A recently developed synthesis (Scheme 94) of pyrido[3, 2 4,5]-thieno[3,2-d]pyrimidines starts with the appropriate iminophosphorane 257, which affords with heterocumulenes the tricyclic pyrimidines 258a-c (94T6705). 

This last section underlines once again the great synthetic potential of the iminophosphorane group, as predicted by Staudinger and Meyer after their first successful synthesis of the P = N double bond. Recently, iminophosphoranes have proved to be novel and versatile heteroannulation components in their reaction with two other components heterocumulenes and heteroarenes (C=X double bonds). 

Due to their high electrophihcity, isocyanates are useful starting materials for the synthesis of heterocycles and C-C bond formation using carbon nucleophiles. A key feature of these reactions is the requirement for more than one equivalent of base. Additionally, a few examples of transition metal-catalyzed homologation of the central carbon of the heterocumulene moiety have been reported. 

Diazo(trimethylsilyl)methyl lithium (3) was found to be the reagent of choice for the synthesis of azoles from heterocumulenes (Scheme 8.43). The reaction is typically carried out in ether at 0-20 °C. Thus, alkyl- (or aryl-)substituted keteni-mines are transformed into 1,2,3-triazoles 188 (246), while C-acceptor-substituted ketenimines yield either 4-aminopyrazoles 189 or 1,2,3-triazoles, depending on the substituents (247). Isocyanates are converted into 5-hydroxy-1,2,3-triazoles 190 (248). Reaction of 3 with isothiocyanates are strongly solvent dependent. 

Ketenes rarely produce [3+ 2]-cycloaddition products with diazo compounds. The reaction possibilities are complex, and nitrogen-free products are often obtained (5). Formation of a cyclopropanone represents one possibihty. Along these lines, the synthesis of (Z)-2,3-bis(trialkylsilyl)cyclopropanones and (Z)-2-trialkylsilyl-3-(triethylgermyl)cyclopropanones from diazo(trialkylsilyl)methanes and appropriate silyl- or germylketenes has been reported (256,257). It was found that subsequent reaction of the cyclopropanone with the diazoalkane was not a problem, in contrast to the reaction of diazomethane with the same ketenes. The high cycloaddition reactivity of diazomethylenephosphoranes also extends to heterocumulenes. The compound R2P(C1)=C=N2 (R = N(/-Pr)2) reacts with CS2, PhNCO and PhNCS to give the corresponding 1,2,3-triazole derivative (60). 

For reviews of cycloadditions of ketenes, see Ghosez O Donnell. Ref. 926 Brady Synthesis 1971, 415-422 Luknitskii Vovsi Russ. Chem. Rev. 1969,38, 487-494 Ulrich Cycloaddition Reactions of Heterocumulenes, Academic Press New York, 1967, pp. 38-121 Holder /. Chem. Educ. 1976, 53, 81-85. For a review of intramolecular cycload-dilions of ketenes to alkenes, see Snider Chem. Rev. 1988, 88, 793-811. 

Synthesis of Heterocycles Using Heterocumulenes Conjugated With Carbonyl Groups O. Tsuge, Kagaku no Ryoiki, Zokan, 1980, 35-69. 

Isocyanates and isothiocyanates are highly reactive heterocumulenes, and are usually only prepared on solid phase as intermediates for the synthesis of ureas, carbamates, thioureas, etc., using methods similar to those used in solution (Table 14.2). 

Carbon dioxide (C02) can interact easily with several N-nucleophiles. Such interaction results in an activation of the heterocumulene, and has a great synthetic relevance as it is a key step towards the carboxylation or, more generally, the car-bonylation of the N-donor substrate and the synthesis of a variety of N-carbonyl compounds. 

The above methodologies, although being intrinsically valuable from a strictly synthetic point of view, are of poor interest in terms of their application. Clearly, the direct synthesis of ureas from amines and the heterocumulene (Equation 6.16), without the use of auxiliary reagents, has a greater practical significance. 

In Figure 4.14, we learned about the Chugaev elimination in connection with the synthesis of alkenes. The second (primary) product of this reaction is the dithiocarbonic acid 5-methyl ester (A). It equilibrates with the zwitterion B, which decomposes into carbon oxysulfide (a heterocumulene) and methanethiol (a heteroatom nucleophile). 

Fig. 8.11. Tandem reaction consisting of three single reactions mutually transforming heterocumulenes and heteroatom nucleophiles in a one-pot synthesis of an isothiocyanate (1) uncatalyzed addition reaction of heteroatom nucleophile (aniline) + heterocumulene (carbon disulfide) —> carbonic acid derivative (A) (2) heterolysis-initiated /3-elimination of the carbonic acid derivative (D) -> heterocumulene (F = phenylisothiocyanate) + heteroatom nucleophile (thiocar-bonic acid O-ethylester) (3) decomposition of a carbonic acid derivative (D) to a heterocumulene (carbon oxysulfide) and a heteroatom nucleophile (ethanol) via the zwitterion H.

Hoesl CE, Nefzi A, Houghten RA, Parallel solid-phase synthesis of 2-Imino-4-oxo-l,3,5-triazino[l,2-a]benzimidazoles via tandem Aza-Wittig/heterocumulene-mediated annulation reaction, J. Comb. Chem., 5 155-160, 2003. 

The starting materials for the industrial synthesis of urea are the nucleophile NH3 and the heterocumulene C02 (Figure 7.3). The reaction starts with the addition of NH3 to... 

Kaugars and Rizzo have found that 5-alkylamino- or 5-arylamino-l,2,3,4-thiatriazoles react with isocyanates to give 3-oxo-A4-l,2,4-thiadiazolin-5-ylureas (65) (79JOC3840). The structures were verified by independent synthesis and by H and I3C NMR spectroscopy. In the presence of triethylamine the exothermic reaction went to completion in a few hours. The reaction may either take place by attack at the amino group to give (63), followed by N2 extrusion to form the reactive dipole (64 equation 31), or the reaction may be initiated by attack at the ring in the 4-position to give an intermediate thiatriazoline, which, as discussed above, reacts with heterocumulenes (see Section 4.28.2.3.l(iii)). As expected, 5-(dialkylamino)thiatriazoles were not found to react with isocyanates. 

Dihydro- 1,3-oxazines (398) are cyclic intermediates in the synthesis of a-amino-y-oxo acid esters by reaction of acyliminoacetates with enamines derived from six-membered ketones240. Sulfur-containing heterocycloadducts 399 and 400 have been prepared by [4 + 2] cycloaddition of enamines to heterocumulenes like thioacyl isocyanates and acyl isothiocyanates241. 

Nina A. Nedolya was born in Irkutsk (Russia) and educated in organic chemistry at the Irkutsk State University (Diploma 1972, PhD 1982, DSc 1998). From 1995 to 1999 she was associated with Prof. L. Brandsma at the Utrecht University (The Netherlands). In 1999 she obtained her second PhD from the Utrecht University. She is presently Head of the Research Group of Chemistry of Heterocyclic Compounds at A. E. Favorsky Irkutsk Institute of Chemistry. She is the author of over 210 review articles and research papers. She is also one of the inventors for 112 patents. She is interested in the chemistry of polyfunctional unsaturated heteroatomic systems (vinyl, allenyl, and alkynyl ethers and their derivatives, linear and cyclic heteropolyenes, hetero-cumulenes), including synthesis of important heterocycles, particularly pyrroles, thiophenes, thiazoles, imidazoles, dihydrofurans, dihydropyridines, pyridines, quinolines, dihydroazepines, and azepines, based on metallated allenes or alkynes and/or heterocumulenes. 

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