Isocyanates, vinyl cycloadditions

The [2+2] cycloaddition reaction of isocyanates proceeds better with olefins having electron donating groups attached to the double bond system. Examples include vinyl ethers, enamines, ketene acetals, tetraalkoxy- or tetraalkylaminooleflns. The more reactive sulfonyl and carbonyl isocyanates undergo cycloaddition reactions with vinyl ethers especially well. For example, the reaction of vinyl ethers with p-toluenesulfonyl isocyanate affords the [2+2] cycloadducts in a stereospecific reaction... 

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

Stereocontrolled synthesis of oxabicyclic (3-lactam antibiotics via [2- -2] cycloaddition of isocyanates to sugar vinyl ethers 96CC2689. 

The palladium-phosphine-catalyzed cycloaddition reactions of vinyloxetanes 530 with aryl isocyanates or diaryl-carbodiimides led to 4-vinyl-l,3-oxazin-2-ones 531 or l,3-oxazin-2-imines 532, respectively (Scheme 101). In the absence of phosphine ligands (PPhs, bis(diphenylphosphino)ethane (DPPE), l,3-bis(diphenylphosphino)propane (dppp), no conversion of heterocumulenes was observed. Starting from fused-bicyclic vinyloxetanes, both types of cycloadditions proceeded in a highly stereoselective fashion, affording only the r-isomers of alicycle-condensed 1,3-oxazine derivatives <1999JOC4152>. 

The other major approach to systems of this type is cycloaddition of cumulene ylides with vinyl isocyanate and vinyl isothiocyanate. Thus, Ph3P=C=C=0 reacts with these two reagents to give 160 and 161 respectively while the corresponding reactions of Ph3P=C=C=NPh afford 162 and 163 <88T543>. By using styryl isothiocyanate with the ketene ylide, 164 was obtained. 

N-Vinyl heterocumulenes represent a new, highly reactive 2-azadiene species, which react, in general, with electron-rich alkenes and alkynes. Accordingly, we think it is of interest to complement the utility of electron-poor 2-azadienes in [4 + 2] cycloadditions by showing some examples involving A-vinyl isocyanates, -isothiocyanates, -carbodiimides, and -ketenimines. 

A direct entry into phenanthridinone and benzophenanthridinone skeletons was also disclosed by the formal [4 + 2] cycloaddition of N-vinyl isocyanates 232 and benzyne (89JOC4019). On the basis of this cycloaddi-... 

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. 

Less satisfactory results have been frequently encountered in the related asymmetric cycloaddition of a vinyl epoxide to an isocyanate as in Scheme 8E.30 [160]. The modest enantioselectivities of this process are indicative of the competitive intramolecular nucleophilic addition with enantioface exchange. When the oxazolidinone was generated from an achiral substrate, somewhat higher enantioselectiviites were obtained presumably due to superposition of the enantioselection obtained in the ionization step. 

M. Chmielewski, Z. Kaluza, and B. Furman, Stereocontrolled synthesis of 1-oxabicyclic /1-lactam antibiotics via [2 + 2]cycloaddition of isocyanates to sugar vinyl ethers, Chem. Commun. (Cambridge), (1996) 2689-2696. 

One of the most facile methods for construction of the (i-lactam skeleton would be [2 + 2] cyclo additions of isocyanates to alkenes. However, the [2 + 2] cycloadditions of alkyl or aryl isocyanides with either 2,3-dihydrofuran or vinyl ethers often fails under normal conditions. High pressure can surmount this difficulty in certain cases. For instance, alkyl isocyanates 125 underwent [2 + 2] cycloadditions with such cyclic vinyl ethers as 126 to produce the P-lactams 127 (Scheme 34) [80]. 

Various unsaturated compounds, such as CO2, isocyanates and aldehydes, undergo Pd-catalysed cycloaddition with vinyl epoxides. Reaction of CO2 with 127 affords cyclic carbonates 128 with retention of the configuration at C(3), offering a method of cis hydroxylation of epoxides [66], and has been used for the synthesis of the side-chain unsaturated (—)-exo-brevicomin (129) [67], The tetrahydrofuran 131 was prepared by [3+2] cycloaddition of activated alkenes such as benzylidene malononitrile (130) with vinyl epoxide via Michael addition and allylation [68],... 

Phenanthridinones.1 Benzyne, generated in situ by Pb(OAc)4 oxidation of 1-aminobenzotriazole (l),2 undergoes [4 + 2]cycloaddition to cyclic vinyl isocyanates to form phenanthridinones. 

Ozonolysis of the cyclic vinyl ethers 71 (n = 2, 3 or 4) in the presence of M-benzylidene-benzylamine affords the dioxazoles 73 by dipolar cycloaddition to transient carbonyl oxides 72. The dioxazoles fragment to mixtures of phenylcycloalkenes, benzaldehyde and N-formyl-benzylamine by the action of silica gel (94JCS2449). Carbonyl oxides 75 (E = C02Me), generated by thermolysis of the peroxides 74, add to phenyl isocyanate to yield 1,2,4-dioxa-zolidin-3-ones 76 (94JCS3295). 

The classical reaction with chlorosulfonyl isocyanate has been extended to it-vinyl sulfide 449 to give a 2.5 1 diastereomeric mixture of 4-(phenylthio)azetidin-2-ones 343 and 450 (Equation 180) <2000MI935>. The facial selectivity in the cycloaddition has been explained by the conformational preference of the allylic groups in the transition structure. A similar reaction with styrene resulted into synthesis of the racemic 4-aryl-azetidin-2-one (Equation 181) <2000TA2351>. The divinyl ether 451 reacted with acid-free chlorosulfonylisocyanate to form 4-vinyloxyazetidin-2-one 452 (Equation 182) <1996SL895, 1997TA2553, 1998TL8349>. Most of the results in the reactions of isocyanate with vinyl ethers could be rationalized by a -conformational preference of the ether in... 

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]. 

Rigby has developed a different approach for the construction of the hydroindolone intermediates65. These compounds were prepared by [1+4] cycloaddition of vinyl isocyanates and isocyanides (Scheme 22). 

W-C4H9) [106, 107]. Ab initio MO calculations have shown that the [2 - - 2] cycloaddition between cis- or Jraw-alkenes and isocyanates to yield y9-lactams takes place by a concerted mechanism in the gas phase, with retention of the alkene configuration in the product. However, increasing solvent polarity contributes to the asynchronicity of the reaction to such an extent that the mechanism changes from a concerted to a two-step process involving a zwitterionic intermediate, with a consequent loss of alkene stereospecificity, as observed in the reaction between chlorosulfonyl isocyanates and vinyl ethers [794]. 

While simple unactivated cyclopropanes have yet to be used for [3 + 2] cycloaddition, Tsuji and coworkers have developed a palladium-catalyzed cycloaddition reaction using electron-deficient vinylcy-clopropanes. Thus, vinylcyclopropane (43) undergoes smooth cyclization with methyl acrylate in the presence of a palladium catalyst to give vinylcyclopentane (44) as a mixture of diasteroisomers (equation 35). The cycloaddition probably proceeds through the zwitterionic ( ir-allyl)palladium intermediate (45) and its stepwise reaction with the acrylate (equation 36). Enones such as cyclopentenone and methyl vinyl ketone will also react. Reaction of the same vinylcyclopropane with phenyl isocyanate produces vi-nyllactam (46) (equation 37).Some cycloaddition reactions with (cyclopropyl)Fp complexes have also been reported. However, the substrates are limited to SO2 and TCNE and the yields have not been disclosed (equation 38). ... 

Hydrolysis of the vinyl groups from the metal center affords olefins. Weiss, Schubert, and Schrock investigated the reaction of the alkylidyne complex W(CCMe3)Cl3(dme) with cyclohexyl isocyanate (208). Two isocyanate molecules are incorporated into the complex as shown in Eq. (212). The reaction was postulated to proceed via a cycloaddition adduct of isocyanate to the metal-carbon triple bond and cleavage of the four-mem-bered ring into metal imido and ketenyl species. Subsequent insertion of a second isocyanate into the metal-ketenyl bond would then give the observed product. 

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