Cyclohexyl isocyanide, reaction with

George and co-workershave investigated the reaction of cyclohexyl isocyanide (185) with DMAD and have shown that a major constituent of the product mixture is the 2 3 adduct (186) formed through a [6 -i- 4] addition of the initially formed intermediate (182) with the dipolar species (181, R = cyclohexyl). Thermal isomerization of 186 in refluxing xylene results in an isomeric spiro compound (187), whereas at higher temperatures, other valence isomers of 186 are formed (Scheme 29). - Winterfeldt had earlier isolated a 1 2 adduct (188) from the reaction of cyclohexyl isocyanide with DMAD. The reaction of some alkyl and aryl isocyanides with acetylenic esters in protic solvents, such as methanol, has been reported to give open-chain adducts with the incorporation of one or two solvent molecules. 

Nair described a reaction in which the 1 1 zwitterionic intermediate generated in situ from dimethyl acetylenedicarboxylate and cyclohexyl isocyanide reacted with a quinone to furnish the spiro-iminolactone as illustrated in the following scheme <03T10279>. 

A novel three-component reaction sequence leading to 5-hydroxy-3-pyrrolin-2-ones has been reported by Liang and coworkers (Scheme 108 2007T8987). Mixing arylaldehyde 410, 2,4-pentanedione (361), and cyclohexyl isocyanide (260) with piperidine gives the 3-pyrrolin-2-one 411. The reaction proceeds via the formation of2-aminofuran intermediates followed by a Dimroth-type rearrangement to the corresponding 3-pyrrolin-2-ones. 

In contrast to the low stereoselections realized in the above syntheses utilizing imines of various chiral aldehydes79-8 1, an almost complete stereoselectivity is reported for the Ugi reaction of 2,3 4,5-bis-O-isopropylidenearabinose with ammonia, acetic acid and cyclohexyl isocyanide giving the 2-acetamino-2-deoxyglueono amides as the exclusive products84. 

Reactions of Pt(PPhj)2(R)X (R = CH3, C Hj X = Cl, Br, I) and methyl isocyanide 144) and analogous reactions of Pd(phos)2(CH3)I (phos = PPh3, PPhMc2) complexes with cyclohexyl isocyanide 169, 170) were reported about the same time. As might perhaps be anticipated, the platinum reactions were slower and one can isolate the intermediate species and observe their rearrangement to the inserted products [Eq. (8)]. The isolation of the... 

Yamamoto and Yamazaki 171) carried out reactions of Pt(PEt3)2CHjI and Pt(PPhMe2)(CH2CjH5)I with tert-butyl and cyclohexyl isocyanides. These reactions gave small yields of the ionic intermediate species, which readily reverted to the appropriate iminoacyl complexes. In reactions of analogous chloride complexes the intermediate species was not isolated. It is suggested on the basis of PMR data that these iminoacyl complexes are five-coordinate (see above). 

One other reaction deserves mention. From bis(cyclooctadiene)nickel and butadiene (31), and in the presence of an isocyanide (RNC, R = cyclohexyl, phenyl, tcrt-butyl) two organic oligomeric products are obtained, 1 -acylimino-11 -vinyl-3,7-cycloundecadiene and 1 -acylimino-3,7,11 -cyclo-dodecatriene. In each, one isocyanide has been incorporated. An analogous reaction with carbon monoxide had been reported earlier. The proposed mechanism of these reactions, via a bis-7r-allyl complex of nickel, is probably related to the mechanism described for allylpalladium complexes above. 

In addition to a-additions to isocyanides, copper oxide-cyclohexyl isocyanide mixtures are catalysts for other reactions including olefin dimerization and oligomerization 121, 125, 126). They also catalyze pyrroline and oxazoline formation from isocyanides with a protonic a-hydrogen (e.g., PhCH2NC or EtOCOCHjNC) and olefins or ketones 130), and the formation of cyclopropanes from olefins and substituted chloromethanes 131). The same catalyst systems also catalyze Michael addition reactions 119a). 

Mono-substituted derivatives of [C5HjMn(NO)(CO)2] (32) and di-substituted (20, 146) derivatives of [CH3C5H4Mn(NO)(CO)2] have been prepared by direct reactions of the isocyanide and [C5H5Mn(NO)(CO)2] or [CH3CjH4Mn(NO)(CO)2]. Brunner and Schindler (32) observe variations of vqq and i no for the series [C5H5Mn(NO)(CO)L]+ (L = phosphines, and cyclohexyl isocyanide) in the order CNC H, > P(OPh)3->--->(PPh3)3 > PBuj. Reactions of the mono- and disubstituted complexes with pentafluorophenyllithium (20,146), and of the disubstituted species with borohydride (148) were noted above. 

Other interesting multicomponent sequences utilizing isocyanides have been elaborated by Nair and coworkers. In a recent example, this group exploited the nucleophilic nature of the isocyanide carbon, which allows addition to the triple bond of dimethyl acetylenedicarboxylate (DMAD) (9-90) in a Michael-type reaction (Scheme 9.19) [59]. As a result, the 1,3-dipole 9-91 is formed, which reacts with N-tosylimines as 9-92 present in the reaction vessel to give the unstable iminolactam 9-93. Subsequently, this undergoes a [1,5] hydride shift to yield the isolable aminopyrroles 9-94. In addition to N-tosylimine 9-92 and cyclohexyl isocyanide (9-89), substituted phenyl tosylimines and tert-butyl isocyanide could also be used here. 

Mixed isocyanide/phosphine complexes can be obtained via several routes. The reaction of the suitable Tc starting material [TcH(N2)(dppe)2] (565) with excess CNBu in MeOH under reflux gave colorless traTO- Tc(CNBu )2(dppe)2] (566) in good yield. The j/cn IR bands appear at 2,049 cm and 2,079 cm for CNBu, and at 2,058 cm and 2,115cm for the corresponding cyclohexyl-isocyanide. The frequencies suggest a strong back-donation from Tc to isocyanide. Since... 

Another example of imidazo[2,l-b][l,3]thiazole formation was reported by Adib et al. in their publication concerning eco-friendly catalyst-free MCR in the water [133]. Reaction of cyclohexyl isocyanide with diverse aromatic aldehydes and 2-aminothiazoles in water at 70°C allowed the isolation of heterocycles 96 in good-to-excellent yields (Scheme 43). According to the spectral data, compotmds 96 were determined as single products of the MCR. 

A facile one-pot synthesis of furopyrans takes place with aromatic aldehydes, cyclohexyl isocyanide, and 4-hydroxy-6-methyl-2-pyrone in the presence of a solid support such as Montmorillonite K-10 (Equation 62) <2005SC535>. The solvent-free reaction, which is enhanced by microwave irradiation, proceeds much more rapidly under these conditions than by conventional methods <2002TL2293>. The one-pot, three-component reaction is also reported to take place rapidly using water as solvent <2004M589>. 

Diazadienes have been shown by various groups to be suitable precursors of imidazoline derivatives by means of [4 + 1 ] cycloaddition reactions. In 1976 Matsuda and co-workers were able to cycloadd heterodienes 303, available from AMrimethylsilyl benzophenone imine and phenyl isocyanate, with cyclohexyl isocyanide to obtain 305 in 91% yield, after methanolysis of the initial adduct 304 [76JCS(P1)1523] (Scheme 67). 

Alkoxy)ethenyl]carbene complexes easily undergo insertion of an isocyanide into the M = C bond.3qn9 Reaction of cyclohexyl isocyanide with [2-(alkoxy)ethenyl]carbene complex ( )-154 yields a 4,5-dihydropyr-rolylidene complex 160 (Scheme 66),169 in agreement with earlier observations of similar reactions of related carbene complexes.17415186... 

The benzo-l,5-oxazocine 523 was obtained utilizing the UgiH-component reaction (IMCR). Reaction of 2-fluoro-5-nitrobenzoic acid 518 with 3-phenylpropionaldehyde 519, cyclohexyl isocyanide 521, and the aminopropanol 520 afforded the Ugi-product 522 which was subjected to treatment with TFA followed by proton scavenging with resin, to promote cyclization to give 1,5-oxazocine 523 (60% yield) (Scheme 105) <2001TL4963>. 

Taking advantage of an intramolecular Wittig reaction, the a-amidoketones 316 underwent annulation to the 3-pyrrolines 317 upon treatment with the ylide 318 <199581151>. These intermediates could be further elaborated to the pyrroles 319 by base-induced elimination of benzenesulfinic acid (Scheme 37) <2000TL8969>. It should also be mentioned that a set of unusual 3-pyrroline-2-ones have been synthesized by Ugi s four-component reactions from phenacylamine hydrochloride, cyanoacetic acid, cyclohexyl isocyanide, and aldehydes, involving final formation of the C(3)-C(4) bond <1999H(50)463>. 

Solubility sol dichloromethane, 1,2-dichloroethane, and diethylene glycol dimethyl ether insol diethyl ether and pentane. Preparative Methods the complex is prepared in situ by the reaction of bis(cyclohexyl isocyanide)gold(I) tetrafluoroborate with (R)-N-[2-(N,N-Dimethylamino)ethyl]-N-methyl-l-[(S)-I, 2-bis (diphenylphosphino)ferrocenylJethylamine, typically in dichloromethane. ... 

The gold(I) complex is prepared in situ by the reaction of (1) with bis(cyclohexyl isocyanide)gold(I) tetrafluoroborate (2), typically in anhydrous dichloromethane. The dihydrooxazolines obtained provide a ready access to enantiomerically pure p-hydroxy-a-amino acid derivatives. High diastereo- and enantios-electivity are generally maintained with a wide variety of substituted aldehydes, and a-isocyanoacetate esters. N,N-Dimethyl-a-isocyanoacetamides and a-keto esters have been substituted for the a-isocyanoacetate ester and aldehyde component, respectively, sometimes with improved stereoselectivity. The effect of both the central and planar chirality of (1) on the diastereo- and enantioselectivity of the gold(I)-catalyzed aldol reaction has been studied. The modification of the terminal di-alkylamino group of (1) can lead to improvements in the stereos-... 

The first multiple insertion of isocyanide into the Pd-C bond of organopal-ladium complexes was reported by Yamamoto in 1970 (Scheme 21) [30]. The reaction of one, two, and three equivalents of cyclohexyl isocyanide with the trans-iodobis(phosphine)methylpalladium(II) complexes 17 yielded the monoimino (18), bisimino (19), and trisimino (20) palladium complexes, re-... 

Application of the Davidson oxazole synthesis to products of the Passerini reaction has expanded the usefulness of this well-known route <91LAll07>. The a-acyloxy ketones or a-acyloxy -keto esters employed in the Davidson synthesis are not readily available. However, the use of arylglyoxals as the carbonyl component of the Passerini reaction, along with cyclohexyl isocyanide and carboxylic acids, gives a wide variety of iV-cyclohexyl-2-acyloxy-3-aryl-3-oxopropionamides (151). Reaction of these intermediates with ammonium formate in acetic acid affords A -cyclohexyl-2,4-diaryl-5-oxazolecarboxamides (152) in fair yields (Scheme 69). 

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