Cycloaddition of carbodiimides

A successful method for preparing 1,3-thiazetidines is the cycloaddition of carbodiimides with isocyanates. The cycloadduct 151 was derived by the interaction of carbodiimide 152 and tosyl isothiocyanate . Reaction of 152 with methyl or phenyl isothiocyanate preferentially leads to iminotriazine-thiones. Cycloaddition between aryl isothiocyanates and dicyclohexylcar-bodiimide produced 153. ... 

Fused 2,4-diimino-l,3-diazetidines 26 obtained by aza-Wittig [2+2] cycloaddition of carbodiimide generated in turn from bisiminophosphoranes were confirmed by X-ray diffraction studies <1992CC424>. 

Cycloaddition Reactions. In [2+2] cycloaddition reactions with car-bodiimides sometimes [2+4] cycloadducts are produced as coproducts. Examples include the reaction of phenylcarbonyl isocyanate, phenylcarbonyl isothiocyanate and thiocarbamoyl isothiocyanate with carbodiimides to give [2+4] cycloadducts, discussed in Section 5.3.1. In the current section, mainly [2+4] cycloaddition of carbodiimides as dienophile with dienes derived from oxoketenes, generated in situ or masked oxoketenes, especially 2,3-diones investigated by Kollenz and his coworkers are discussed. 

Cycloadditions of isocyanates and their derivatives with vinyiaziridines were first reported by Alper and coworkers. From their previous studies of cydoadditions to vinylepoxides or alkylaziridines, they investigated cydoadditions to vinyiaziridines and found that such reactions with isocyanates, carbodiimides, or isothiocyanates in the presence of catalytic amounts of Pd(OAc)2 (2 mol%) and PPh3 (10 mol%) at room temperature afforded five-membered ring products 249 in 34—97% yields (Scheme 2.61) [91]. When an aziridine 247 possessing an alkyl substituent at the... 

Scheme 65) <60G1290>. Oxadiazolines (156) are produced by cycloaddition of cyanamides and nitrile oxides aryl (Scheme 66) <66JPR22l>. Thus, for un- and monosubstituted cyanamides, cycloaddition occurs to the C=N double bond of a tautomeric carbodiimide form rather than to a nitrile triple bond. On the other hand, dicyandiamide (157) and benzonitrile oxide furnish (158) (Scheme 67). 

General syntheses of 1,3-diazetidines are [2 + 2] cycloadditions of C = N-containing substrates (Scheme 26). Dimerization of imines and isocyanates furnishes substituted 1,3-diazetidines. Cycloaddition of isocyanates to carbodiimides and isocyanates with imines are alternative syntheses,... 

Asymmetric cycloaddition of 2-vinyloxiranes to carbodiimides proceeds in the presence of Pd2(dba)3-CHC13 and TolBINAP as the chiral ligand in THF at room temperature to yield 4-vinyl-l,3-oxazolidin-2-imines with up to 95% ee [74] (Eq. 8A.50). The enantio-determining step is assumed to be the nucleophilic attack of a nitrogen nucleophile on a 7i-allylpalladium intermediate. Reactions of 2-vinyloxiranes with isocyanates using the same catalyst system afford 4-vinyl-l,3-oxazolidin-2-ones with low enantioselectivity. 

The palladium complex derived from TolBINAP catalyzes cycloaddition of vinyl epoxide to a carbodiimide with high enantioselectivity (Eq. 8E.12) [166], The stereochemical course of the cycloaddition of the epoxide with the heterocumulene was noticeably influenced by the structure of... 

The metathetical reaction of C02 with metal (Ti(IV), U(V)) arylimido-complexes led to an arylisocyanate and a metal-oxo species [4g, 115a]. In these processes, which take place under very mild conditions (ambient temperature and pressure), the metal center acts as the sink for unrequired oxygen. A common feature which characterizes these transformations from a mechanistic point of view is the intermediate formation of a metal carbimato-species through the [2+2] cycloaddition of C02 with the metal-imido complex (Scheme 6.23). By cycloreversion, the four-membered aza-metalla-cycle then converts into isocyanate and a stable metal-oxo complex. These processes, at least formally, are reminiscent of the reaction of imino-phosphoranes with C02 to give isocyanates and carbodiimides [115b,c]. 

The nitrene 28 is not produced from the azide precursor, but from heterocycles via photolysis and thermolysis as shown in Sch. 11 [20]. Iminoacyl nitrenes react intramolecularly giving benzimidazoles with good yields (Sch. 11), and, dependending on the precursor used and the reaction conditions, varying amounts of carbodiimides are obtained. The reactivity of the acyl nitrenes is influenced by the substituent connected to the acyl group (see Sch. 10), however all acyl nitrenes are quite reactive and therefore rather unselective. Apart from cycloaddition reactions with Tt-bonds, insertion reactions into a-bonds, additions to lone pair electrons of... 

General syntheses of 1,3-diazetidines 200 are [Z + Z] cycloadditions of C=N-containing substrates (Scheme 95) . The dimerization of aryl isocyanates 199 to l,3-diarylazetidin-2,4-diones is one of the classical methods for the synthesis of 1,3-diazetidinones. Carbodiimides 201 undergo [Z + Z] cycloaddition reactions to... 

The palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a [42] and aziridine 20b [39] with the activated olefin 4a for the formation of five membered cyclic ether 21a and pyrrolidine derivative 21b has also been reported in our laboratories. The mechanistic issue is very much similar to that discussed in Scheme 9. Pd(0) catalyst added oxidatively to 20 to produce the 7r-allylpalladium complex 22. The Michael addition of a hetero nucleophile in 22 to the activated olefin 4a gives 23 which undergoes intramolecular nucleophilic attack on the inner 7r-allylic carbon atom to give the cy-clized products 21 and Pd(0) species is generated (Scheme 10). Similarly, the palladium-catalyzed [3 + 2] cycloaddition of vinylic oxirane 20a with the N-losylimincs 24 is also known (Scheme 11) [43]. Intermolecular cycloaddition of vinyl epoxides and aziridines with the heterocumulenes such as isocyanates, carbodiimides and isothiocyanates is also known [44,45]. Alper et al. reported the regio- and enatioselective formation of the thiaolidine, oxathiolane, and dithiolane derivatives by the palladium-catalyzed cyclization reaction of 2-vinylthiirane with heterocumulenes [46]. 

I would like to acknowledge the contributions of my former co-workers at the Donald S. Gilmore Research Laboratories of the Upjohn Company, especially Dr R.H. Richter and B. Tucker who were involved in the synthesis and cycloaddition reactions of carbodiimides Dr L.M. Alberino who participated in the synthesis of polycarbodiimides Dr K. Onder and Dr WJ. Farrissey, Jr, who played a major role in the development of thermoplastic polyamides based on carbodiimide chemistry Dr H.W. Temme and Dr C.P. Smith, who developed novel polymeric catalysts for the conversion of isocyanates into carbodiimides and A. Odinak, who developed the liquid MDI process. 1 would especially like to acknowledge the encouragement of the late Dr A.A.R. Sayigh. 

The cycloaddition of chiral (-)menthylcarbodiimide with prochiral ketenes affords chi-rally selective cycloadducts In the reaction of an optically active alcohol with dicy-clohexylcarbodiimide complete inversion of the configuration occurs after hydrolysis. " Treatment of arenesulfenic acids with alcohols, thiols or secondary amines in the presence of optically active carbodiimides affords the corresponding optically active arenesulfenic acid derivatives. DCC is used to convert an optically active selenoxide into the corresponding optically active selenimide with TsNHa. ... 

Cycloaddition Reactions Across C—C Multiple Bonds. Cycloadducts derived from carbodiimides and olefins or allenes are not known. However, the [2+2] cycloaddition of ketenes, R2C=C=0, to carbodiimides affords 4-imino-2-azetidinones (/3-lactames) 239 in high yield. Aliphatic carbodiimides show higher reactivity in comparison to aromatic carbodiimides, and the reaction proceeds across the aliphatic C=N bond in N-alkyl-N -arylcarbodiimides. The cycloadducts obtained in this reaction are listed in Table 2.3. 

Cycloaddition Reactions. Carbodiimides also react as dipolarophiles in [2+3] cycloaddition reactions. For example, generation of diphenylnitryl imine 292 in the presence of diphenylcarbodiimide affords a spiro compound 293 as the result of the reaction of the initially formed [2+3] cycloadduct with a second equivalent of the nitrile imine. ... 

Carbodiimides readily undergo reactions across their C=N bonds to form heterocycles. For example, in their di- and trimerization reactions four and six membered ring N-hetero-cycles are obtained (see Section 2.4.1). Also, numerous four, five and six membered ring heterocycles are formed in the cycloaddition reactions of carbodiimides, often in excellent yields (see Section 2.4.2). Nucleophilic reactions of carbodiimides sometimes give rise to... 

The reaction of thiosalicyclic acid 614 with two equivalents of carbodiimides may involve a thioacylketene intermediate 615, which undergoes a [2+4] cycloaddition reaction with the second equivalent of the carbodiimide to give the cycloadduct 616.5 ... 

Also, the one pot reaction of heterocyclic bis-iminophosphoranes with one or two equivalents of aryl isocyanates leads to selective formation of fused heterocycles. For example, from the pyrazole derivative 17 either [l,3]-diazepines 18 or tricyclic ring systems 19 are formed. The latter reaction involves an intramolecular [2-1-2] cycloaddition of both carbodiimide substituents. ... 

Carbodiimides also play a role as building blocks of numerous N-heterocycles. Examples are the cycloaddition reactions of carbodiimides. In the formation of [2-1-2] cycloadducts N-methyl-N -t-butylcarbodiimide is used as a marker to determine the mode of addition of isocyanates or isothiocyanates to carbodiimides. In these reactions addition across the C=N or the C=0 bond of the isocyanate or across the C=N or the C==S bond of the isothiocyanate can occur. Addition to the N-methyl-N -t-butylcarbodiimide always proceeds across the N-methyl double bond. Also, theretroreaction of the [2-1-2] cycloaddition reaction of carbodiimides can afford a different set of heterocumulenes. ... 

Cycloaddition of sulfenes to Schiff bases (e.g., 434) and carbodiimides yields 1,2-thiazetidine 1,1-dioxides and 3-imino derivatives. A concerted mechanism was suggested. An earlier report of the cycloaddition of a sulfene to a Schiff base lacked proof for the structure of the adduct. Best yields are obtained with two equivalents of imine. The cis isomers can be converted to trans by treatment with triethylamine. ... 

The cycloaddition of isothiocyanates to imines gives 2-imino-l,3-thiazetid-ines, some of which are unstable.Cycloaddition of carbodiimines to bis(trifluoromethyl) ketene and isothiocyanates " gives 2,4-bis-imino-l,3-thiazetidines. The reaction of carbodiimides with 0,0-dimethyldithiooxalate to give 1,3-dialkyl-5,5-dimethoxy-2,4-imidazolidinedithiones... 

---