Isocyanide-insertion product

Although reaction of organozirconocene compounds fails with most organic electrophiles, treatment with sterically unhindered isocyanides, such as rcBuNC, is possible." Organometallic species 24 attacks nBuNC 25 to give isocyanide-insertion product 26, which is finally hydrolyzed to the one-carbon homologated aldehyde 6. 

Vinyl zirconocene derivatives react also with sterically unhindered isocyanides, such as n-BuNC, to give the isocyanide-insertion products. Acidic hydrolysis leads to the corresponding one-carbon homologated aldehydes in good yields (Scheme 12.31) [41]. 

Rh(OEP)H reacts with CNR (R = Me, n-Bu,) to give the adduct Rh(OEP)-(H)CNR (which has no parallel in CO chemistry) which then slowly transforms to the formimidoyl insertion product, Rh(OEP)C(H)=NR. The dimer Rh(OEP))2 reacts with CNAr (Ar = 2.6-Cf,H3Mc2) in aqueous benzene to give the carbamoyl product. Rh(OEP)C(0)NHAr (characterized by an X-ray crystal structure) together with the hydride, which it.self reacts further with the isocyanide. This is suggc.sted to form via a cationic carbene intermediate, formed by attack of HiO on coordinated CNAr in concert with disproportionation to Rh(III) and Rh(l). 

In the reaction of Ni(CNBu )4 and methyl iodide oligomerization of the isocyanide was observed the only isolable nickel complex was (I), shown below. This product is believed to arise through sequential insertions of three isocyanides into a nickel-carbon bond. Upon further treatment with additional isocyanide at a temperature greater than 60° C one obtains a polymer (RNC) presumably through multiple isocyanide insertion reactions. The addition of benzoyl chloride to Ni(CNBu )4 gave two isolable compounds Ni(CNBu )3(COPh)Cl (74%) and (II) (8.2%). This latter reaction, and the isolation of (II) in particular, suggests that the proposed mechanism for polymerization of isocyanides is reasonable. 

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... 

The indazoline products can also be made directly from the palladium complexes 78 by heating them with the isonitrile in toluene at 120CC.162 They are also formed in dicobalt octacarbonyl-catalyzed reactions of azo-arenes with isocyanides but in this case an alternative reaction pathway leading to indazolo[2,l- ]indazoles (79) is observed (Scheme 96).163 Products of the latter type are formed from sterically hindered isocyanides hence it is likely that in these cases a double metallation is favored over isocyanide insertion into a monometallated species (Scheme 97). 

The only carbene-like reaction reported so far is the low-temperature addition of tert-butyl isocyanide to carbenes 2d and 2u.78 From the P-hydrogenophosphonio carbene 2d, the heterocycle 89 was isolated in high yield. It is believed that the initial coupling product 87d rapidly inserts a further equivalent of isocyanide into the P-H bond, leading to the intermediate 88, which then undergoes rapid elimination of diisopropylamine. When the same reaction was performed with the P-chloro(phosphonio)car-bene 2u, a 1/1 mixture of keteneimine 90 and phosphinonitrile was obtained. This result can be explained by the cleavage of the carbene-isocyanide coupling product 87u by residual HCN, inherently present in the f-BuNC. 

Facile isocyanide insertion reactions into metal-carbon, -nitrogen, -sulfur, -oxygen, - hydride, and - halide bonds have been found to readily occur. The insertion into metal-hydrides to give stable formimidines is particularly noteworthy since corresponding formyls (—CHO) are exceptionally difficult to synthesize and tend to be very unstable. There is a great deal of interest in carbon monoxide reductions, and the instability of the intermediate reduction products has made a study of the reduction process extremely difficult. Recently, however, the interaction of isocyanides with zirconium hydrides has allowed the isolation of the individual reduction steps of the isocyanide which has provided a model study for carbon monoxide reduction (39). 

The structurally novel antimitotic agent curacin A (1) was prepared with an overall yield of 2.5 % for the longest linear synthesis. Three of the four stereogenic centers were built up using asymmetric transformations one was derived from a chiral pool substrate. Key steps of the total synthesis are a hydrozirconation - transmetalation protocol, the stereoselective formation of the acyclic triene segment via enol triflate chemistry and another hydrozirconation followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A (1) the oxazoline - thiazoline conversion provides efficient access to the sensitive marine natural product. 

Products of type (21-XXX) are quite common for isocyanide insertions (see later). 

The 2-oxoaUtyl polymer 82 reacts with isocyanides RNC to give 83, probably through the insertion product 84, followed by a tautomerization . 

In the inserted product, M and R can be bonded to the same atom of L (1,1-insertions) or to two different atoms (l,n-insertions, with n designating the number of atoms constituting the inserted sequence). Thus, for example, 1,1-insertions [see reaction (b)] are observed with CO and with isocyanides in the more frequent type of coordination, carbon being the bridging atom in both cases, while 1,2-insertions are found with olefins, acetylenes, and carbon dioxide [reactions (c)-(f)] the -bond type, which is frequently encountered with early transition metal elements and with / element compounds for both carbon monoxide and isocyanides, is in fact a case of 1,2-insertion (see 11.3.2.1.5-11.3.2.2). 

Alkyl- and arylisocyanides are electronically similar to CO and give insertions with transition and non-transition metal complexes. When a metal-alkyl derivative containing coordinated carbon monoxide is treated with an isocyanide, two products are possible [reactions (a) and (b)], depending on whether the inserted fragment is carbon monoxide or the isocyanide, respectively. 

As stated earlier, (11.3.1), the multiple insertion of carbon monoxide into the same metal-hydrocarbyl bond is a rather elusive reaction. On the other hand, multiple insertion of isocyanide has been reported for nickel(II). For example, when the nickelfO) derivative Ni(t-BuNC)4 was treated with Mel in hexane at RT, consecutive insertion of three RNC groups was observed to give the product of reaction (e), as a consequence of a primary oxidative addition of the alkyl iodide to the nickel(O) complex. It is interesting that one of the two terminal fragments of the five-membered metallacycle is reminiscent of an arrangement of the first insertion product. 

Similar insertion reactions have been found for the palladium(II) complex that results from reaction (f), which reacts with o-xylyl-isocyanide to give the triple insertion product, with a five-membered ring including palladium. 

Polymerization of isocyanides is a thermodynamically feasible process, in agreement with the stoichiometric multiple insertion observed in reactions between metal-alkyl complexes and isocyanides. The entropy loss in the case of isocyanides is lower than for insertion of CO. Isocyanide insertions into palladium-alkyl a bonds are faster than those for the platinum(II) analogues. The latter, on the other hand, usually lead to more stable and better defined products. Insertion of isocyanides into platinum-carbon bonds has been studied extensively Reaction (j) is typical the ionic product was strongly suggested by observation that the compounds isolated under mild conditions are 1 1 electrolytes. 

The reactions of Ti(CH2Ph)2(cb)2 and (cb)2Ti(/x-CHSiMe3)2Ti(cb)2 (cb = carbazole) with 2,6-dimethylphenyl isocyanide lead to titanium derivatives containing new carbon-carbon bonds (Scheme 130). The molecular structures of the insertion products have been determined by X-ray diffraction.109 Reaction of Ti(CH2Ph)2(cb)2 with 2,6-dimethylphenyl isocyanide (xylNC) gives the double insertion product bis(iminoacyl) derivative. The iminoacyl... 

The product distribution depends on the isocyanide used. Only with aromatic (R = o-tolyl or 2,6-xylyl), and not with aliphatic isocyanides (R = Bu , Bu or benzyl) are isonitrile insertion products 24 formed. Aryl isocyanide insertion is obviously very fast since the competing formation of 23 from CO insertion is not observed complexes 22 are only minor products. With aliphatic isocyanides, the thpp complexes 22, from double cycloaddition of dmad cf. Section 3.1.1), are the major products (70 to >95% of the product mixture) and indicate a strongly increased 1,3-dipolar reactivity, i.e. the intermolecular second cycloaddition is preferred to the intramolecular CO insertion. Compared with the ruthenium compound 17, the thpp in 22 is strongly bound to the metal and can only be decomplexed oxidatively with cerium(iv), or under 80 bar of CO. 

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