Primary amines, derivatives isocyanide reaction

Isocyanides can be reduced to the corresponding hydrocarbons by (TMS)3SiH. The reaction can be considered as a smooth route for the deamination of primary amines. An example is given in Reaction (20). The key step for these chain reactions is expected to be the fragmentation of the intermediate radical derived from the fast addition of (TMSlsSi radical to the terminal carbon atom. 

The nitrogen atom in a-ferrocenylalkylamines generally shows the same reaction pattern as that in other amines alkylation and acylation do not provide synthetic problems. Due to the high stability of the a-ferrocenylalkyl carbocations, ammonium salts readily lose amine and are, therefore, important synthetic intermediates. Acylation of primary amines with esters of formic acid gives the formamides, which can be dehydrated to isocyanides by the standard POClj/diisopropylamine technique (Fig. 4-16) [92]. Chiral isocyanides are obtained from chiral amines without any racemization during the reaction sequence. The isocyanides undergo normal a-addition at the isocyanide carbon, but could not be deprotonated at the a-carbon by even strong bases. This deviation from the normal reactivity of isocyanides prompted us to study the electrochemistry of these compounds, but no abnormal redox behaviour, compared with that of other ferrocene derivatives, was detected [93]. The isocyanides form chromium pentacarbonyl complexes on treatment with Cr(CO)s(THF) (Fig. 4-16) and electrochemistry demonstrated that there is no electronic interaction between the two metal centres. 

Tosylmethyl isocyanide (TosMIC) (75 R = H), a versatile reagent in synthesis, can also be used as an acyl anion equivalent. For instance symmetrical and unsymmetrical diketones were prepared by using this TosMIC synthon (equation 40). Ketones are homologated to enones by alkylating the condensation product derived from TosMIC, followed by acid hydrolysis (Scheme 46). 1-Isocyano-l-tosyl-l-alkenes (76), formed by the reaction of TosMIC with an aldehyde or ketone, react with a primary amine or ammonia to give 1,5-disubstituted (or 5-monosubstituted) imidazoles in high yield (Scheme 47). ... 

The conversion of the BOC group to other carbamates is achieved by heating with an alcohol, Ti(0-i-Pr)4 in toluene. Teoc-, Cbz- and Alloc-protected primary amines have been prepared in this fashion. The reaction is selective for a primary BOC derivative probably because the reaction proceeds through an isocyanide. ... 

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

Besides the formation of oxazole derivatives, Schollkopf and the others have successfully extended the a-alkali metalated isocyanides to the formation of the chain-extended primary amines, 2-oxazolines, 2-thiazoline-4-carboxylic esters," 2-imidazolines, 2-pyrrolines and pyrroles, thiazoles, 2-imidazolin-5-ones," 2-imidazolinones," etc. For example, a simple reaction between lithiomethyl isocyanide with two equivalents of piperonal followed by acetylation of the intermediate with acetic anhydride affords the corresponding oxazoline. ... 

A. Massoudi, I. Amini, A. Ramazani, F. Z. Nasrabadi, Y. Ahmadi, Bull. Korean Chem. Soc. 2012, 33, 39-42. Four-component synthesis of 2-(V,V-diaIkylamino)-2,4-6-cycloheptatrien-l-one derivatives from tropolones, an isocyanide, a primary amine and an aldehyde via Ugi-Smiles coupling reaction. 

During the first month of this experiment, it was realized that this reaction is extremely variable. Thus, diverse amines (ammonia, primary and secondary amines, hydrazine derivatives, hydroxylamines) 13, carbonyl compounds (aldehydes, ketones) 14, acid components 15 or their anions (H2O, Na2S203, H2Se, R2NH, RHN-CN, HN3, HNCO, HNCS, RCO2H, RCOSH, ROCO2H, etc.), and the isocyanides could form the a-adducts 16 that rearrange into their products 17 (Scheme 1.5). 

Strain in the intermediate produces an overall decrease in the rate such that reversible attack by amine on the isocyanide carbon becomes comparable in rate with subsequent stages leading to carbene formation. Steric factors are also cited in explanation of the fact that with bis-isocyanide complexes c -[PdCl2(CNAr )2] secondary amines give only monocarbene derivatives c -[PdCl2 C(NHAr )NRAr CNAr ] whereas relatively unhindered primary anilines react further to give bis-carbene complexes c/s-[PdCl2 C(NHAr )NHAr Ij]. Reaction (18) (Ar = />-MeCeH 4) carried... 

Moreover, the use of the convertible 2-(2,2-dimethoxyethyl)phenyl isocyanide in the Ugi-4CR enabled interesting post-polymerization modification opportunities [22]. Similarly to the use of Passerini monomers, many grafting-onto reactions could be realized using primary and secondary amines or lithium hydroxide to afford the corresponding amide- or carboxylic acid-functionalized polymers, respectively. Interestingly, the conversion into the amide was not possible via the Passerini approach as a result of the weak polyester backbone. However, because Ugi CR-derived polymers contain amide bonds, harsher reaction conditions are... 

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