Aliphatic isocyanides

Liquid crystals based on aliphatic isocyanides and aromatic alkynyls (compounds 16) show enantiotropic nematic phases between 110 and 160 °C. Important reductions in the transition temperatures, mainly in clearing points (<100 °C), areobtained when a branched octyl isocyanide is used. The nematic phase stability is also reduced and the complexes are thermally more stable than derivatives of aliphatic alkynes. Other structural variations such as the introduction of a lateral chlorine atom on one ring of the phenyl benzoate moiety or the use of a branched terminal alkyl chain produce a decrease of the transition temperatures enhancing the formation of enantiotropic nematic phases without decomposition. 

MCR also tolerates the aliphatic isocyanide functionality [150], thus allowing the union with various IMCRs. Finally, we developed the first example of a triple MCR process (SCR toward 83) based on our 2//-2-imidazoline (65) and W-(cyano-methyl)amide (32) MCRs united with the Ugi-4CR (Fig. 25). 

The present procedure is the best way of preparing aliphatic isocyanides boiling above ethyl isocyanide. It has been applied to the synthesis of the following isocyanides 6 isopropyl (38%), -butyl (61%), te -butyl (68%), and benzyl (56%). In preparing isopropyl isocyanide or teri-butyl isocyanide, the petroleum ether should be of boiling point 30-35°, as otherwise it is difficult to separate these low-boiling isocyanides in the indicated yield, and,... 

Among the features of Volume 41 is the smallest-scale synthesis yet published in Organic Syntheses, namely, the preparation of 0.0005 mole of cholestanyl methyl ether by a generally useful methylation procedure that employs diazomethane and fluoboric acid (p. 9). Two preparations of isocyanides by dehydration of formamides are included. One of these, illustrated by cyclohexyl isocyanide (p. 13), is most suitable for aliphatic isocyanides while the other, illustrated by o-tolyl isocyanide (p. 101), is most suitable for aromatic isocyanides. 

Peptides. This isocyanide is preferable to simple aliphatic isocyanides (9, 82) for coupling of amino acid derivatives to peptides. Addition of hydroxysuccinimide (9,246) or 1 -hydroxybenzotriazole (6,288) suppresses racemization. It is important to allow the acid component and the additive to react with the isocyanide for a suitable period before addition of the amine component and triethylamine or DMAP. Coupling to di- and tripeptides in yields of 55-72% have been reported. The byproduct, (N-morpholinoethyl)formamide, is removed by an acid wash. 

The a-isocyanide is a-acidic and will react in the SCR to yield 2/f-2-imidazolines, while the other isocyanide is an aliphatic isocyanide and remains unaffected. 

Peptides. In the presence of an aliphatic isocyanide, amino acids and amines condense to form amides. Yields are increased by addition of ZnCl, CH2CI2 is preferable to alcoholic solvents. Yields of dipeptides range from 25 to 90%. ... 

Nickel (0) and palladium (0) derivatives of this class are known. The nickel derivatives were first obtained by complete replacement of the carbon monoxide of Ni(CO)4 by aromatic isocyanides (PI, 96, 115, 116). With aliphatic isocyanides the reaction is more difficult. Hieber 91, 96) obtained the only trisubstituted methylisocyanide derivative, NiCO-(CNCH3)3, but recently Bigorgne 18, 21), who studied the reaction... 

Isocyanides CNR can act as terminal ligands or as a group to insert into an M—R bond, M—C(NR)R. The reaction of the benzyl manganese(I) derivatives Mn(CH2Ar)(CO) with aliphatic isocyanides ... 

A series of achiral isocyanides was polymerized using a catalyst prepared from (t-BuNC)4Ni(II)(Cl04)2 (46a) and (S)-47 [59]. It turned out, however, that only a few isocyanides, including 1,1-dimethylpropyl, 1-methyl-1-phe-nylethyl, and 2,6-dichlorophenyl isocyanides, yielded optically active polymers. All primary and secondary aliphatic isocyanides, and aromatic aldehydes, except for a 2,6-dichlorophenyl derivatives, yielded optically inactive polymers. There appears to be a tendency that only sterically congested isocyanides permit the induction of a screw-sense. 

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. 

The labilisation of the coordinative bonds due to the strong cr-donation of the aliphatic isocyanide ligands in 25a,b, which has already been mentioned above, obviously also plays a role again in the reaction of 25a,b with aryl isothiocyanates (Scheme 7). The X-ray structure of 34c, L = Bu NC indicates a [3.2.0] bicyclic complex with a coordinated amido nitrogen and an uncoordinated imine nitrogen (A). However, temperature-dependent NMR spectroscopy indicates a dynamic competition of these two nitrogen atoms for the coordination site. As in all previous cases, the terminally coordinated aliphatic isocyanides do not insert in the initial bicyclo[2.2.1] cycloadduct, but rather an external isothiocyanate is inserted, most likely after precoordination by displacement of the imino group. 

The reaction proceeds in chloroform at room temperature however, no yields are reported. In the aliphatic series it is sometimes advantageous to conduct the reaction in diethyl ether, using sulfuryl chloride as the chlorinating agent. Thus, ethylcarbonimidoyl dichloride VIII is obtained in the reaction of ethyl isocyanide with sulfuryl chloride However, addition of chlorine to long-chain aliphatic isocyanides does not produce the corresponding carbonimidoyl dichlorides ( ). 

Pyridine iV-oxides can be aminated with isocyanides (Scheme 33). The reaction proceeds through an N-formylaminopyridine intermediate that can be isolated or hydrolyzed with acid to provide the aminopyridines.The reaction works with a number of substituted pyridines however, with electron-withdrawing groups the yields are lower. With C-3 substituted pyridine iV-oxides, a mixture of regioisomers was produced. The C-2 product predominated with aryl isocyanides. Steric hindrance did appear to impact the yield for both aryl and aliphatic isocyanides. Finally, isoquinoline AT-oxide reacted under these conditions to form the aminoisoquinoline in good yield (60%). If both the two and six positions were blocked, the reaction failed to proceed (14JOC2274). 

Both aromatic and aliphatic isocyanides including a-isocyanoacetate provided a-ketoamides with moderate to good yields. However, the sterically hindered tert-butyl isocyanide provided the coupling product in low yield. Ahphatic aldehydes including functionalized ones are effective substrates. With a-amino aldehyde, N,N-double protection of the a-amino group was crucial for the reaction to occur properly. Chiral aldehyde 110 has been efficiently transformed into the corresponding... 

Metal-mediated DCA between azides and isocyanides typically starts from metal-azide complexes and free isocyanides. Thus, the azido complexes [RhCp (/u-N3)(N3)]2 (Cp = rj-C Me ), trani-Rh(N3)(CO)(PPh3)2, Na2[Pd(N3)4], Na2[Pd2(/u-N3)2(N3)4], and Na[Au(N3)4], reacted with aliphatic isocyanides to give a series of new metal-carbon bonded tetrazolato complexes [40]. All azide ligands in the coordination sphere undergo this cycloaddition with isocyanides except on palladium(II), where only two tetrazol-5-ato groups are formed (12, Scheme 13.11). 

At room temperature, treatment of 2-6a with 1.2 equivalents of aliphatic isocyanide t-BuNC led to the mono-insertion of isocyanide into the Zr-C(sp ) a bond giving 2-14a in 91 % isolated yield (Scheme 2.10a). Even in the presence of excess amount of t-BuNC, only 2-14a was obtained and the double-insertion product was not observed, probably due to the steric hindrance of t-Bu group. Similarly, the insertion of t-BuNC into tolyl-substituted 2-6b gave 2-14b under the same condition (Scheme 2.10b). However, when 2.4 equivalents of less steric-hindered isocyanide CyNC were used, the double-insertion product 2-15 was formed exclusively in 78 % isolated yield (Scheme 2.10b), showing that the steric hinderance of isocyanides strongly affects the insertion reaction. The double-insertion product 2-16 could also be obtained in good isolated yield when 2.4 equivalents of 2,6-dimethylphenyl isocyanide were used to react with 2-6a (Scheme 2.10c). It should be noted that... 

---