Isocyanide reagents

Convertible isocyanide reagent 66 allows a mild and chemoselective in situ post-Ugi activation of the isonitrile bom amide with simultaneous deprotection of the nucleophilic amine, that is, liberation and activation of two Ugi-reactive groups, if desired also under subsequent lactam formation [33]. Another recently introduced convertible isocyanide, l-isocyano-2-(2,2-dimethoxyethyl)-benzene 73, was shown effective by Rhoden et al. In the course of this short sequence, a hydrolytically labile W-acylindole 78 is formed, which is displaced intramolecularly by the amine portion of the former Boc-protected amino acid 75 (Scheme 13). 

Electrophilic addition to anionic molybdenum isocyanide derivatives [Na][Tp Mo(CNR)(CO)2] is dominated by direct attack at nitrogen to form alkylidyne products however, alkylation at the metal followed by isonitrile insertion can lead to j -iminoacyl complexes in some cases. The aminocarbyne products Tp Mo(=CNRMe)(CO)2 are formed in high yield for methyl and phenyl isocyanide reagents. However, the formation of the corresponding tcrt-butylamino-alkylidyne complex is accompanied by formation of f/ -acyl and / -iminoacyl complexes (Scheme 22). ... 

It is important to note that the Petasis reaction in Scheme 8.5 is a more convenient method for preparation of a-amino acids than, for instance, Strecker or Ugi syntheses The latter two rely on the use of undesirable cyanide ion or isocyanide reagents, and require more stringent experimental conditions. More details on both reactions are given in the next section. 

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

Tolylaulfonylmethyl isocyanide is a useful and versatile reagent in organic chemistry. It has been used for the synthesis of several azole ring systems by base-induced addition of its C—N=C moiety to various... 

Synthetic applications of organosulfur reagents are expanding rapidly. Stable sulfuranes are included for the first time in BIS[2,-2,2-TRIPLUORO-l-PHENYL-l-(TRIFLUOROMETHYL)ETHOXY] diphenyl SULFURANE and DIETHYLAMINOSULFUR TRI-FLUORIDE. The latter is used to transform an alcohol to a fluoride in p-NITROBENZYL FLUORIDE. The direct homologation of a ketone to a nitrile by use of p-TOLYLSULFONYLMETHYL ISOCYANIDE is illustrated in 2-ADAMANTANECARBONITRILE. Reagents with... 

Scheme 21 Synthesis of isocyanides from amines using PS-reagents...

When the reagent is the thiocyanate ion, S-alkylation is an important side reaction (10-43), but the cyanate ion practically always gives exclusive N-alkylation. ° Primary alkyl halides have been converted to isocyanates by treatment with sodium nitrocyanamide (NaNCNN02) and m-chloroperoxybenzoic acid, followed by heating of the initially produced RN(N02)CN. ° When alkyl halides are treated with NCO in the presence of ethanol, carbamates can be prepared directly (see 16-7). ° Acyl halides give the corresponding acyl isocyanates and isothiocyanates. For the formation of isocyanides, see 10-111. 

Isocyanides that do not contain an a hydrogen react with alkyllithium compounds, as well as with Grignard reagents, to give lithium (or magnesium) aldimines. These metalated aldimines are versatile nucleophiles and react with various substrates as follows ... 

Isocyanides can be prepared by elimination of water from N-alkylformamides with phosgene and a tertiary amine. Other reagents, among them TsCl in quino-... 

The reactions of nucleophilic reagents with cationic and uncharged metal carbonyl complexes have received much attention in the past, and it is not surprising that these studies have now been extended to isocyanide metal complexes. Different products in these reactions can arise by three general routes these include ligand substitution, reactions involving attack at a ligand, and reduction of the metal complex. All have been observed in reactions with metal isocyanide complexes. 

Aumann and Fischer (7), as part of a larger project on carbene-metal complexes, have investigated the reaction of Cr(CO)5C(OCHj)CH3 and cyclohexyl isocyanide. They describe an initial 1 1 adduct of these reagents, to which they ascribe structure (XX) it is interesting to note that neither... 

No isocyanide was obtained when 2-nitro-5-methoxyformanilide was treated with the carbonyldiimidazolium reagent.[ 116]... 

Transition metal isocyanide complexes can undergo reactions with nucleophiles to generate carbene complexes. Pt(II) and Pd(II) complexes have been most extensively investigated, and the range of nucleophilic reagents employed in these reactions has included alcohols, amines, and thiols (56) ... 

Borylphosphinoethene derivatives were synthesized by varying the dipolar reagents. Thus, (176) appeared to interact with /-butyl isocyanide as trialkylborane, yielding unstable iminoborane 178. The latter forms 2-phosphinoethenyl-l-bora-2,4-diazacyclopentane (179) with ben-zalaniline and 1 -hydroxy-1 -phosphinoethyl-1 -borata-2-ammonia-4-aza-cyclopentane-2 (180) with acetonitrile [Eq. (134)] (90IZV2147). 

Aldehydes.1 This Wittig-Horner reagent (available from Fluka) converts aldehydes or ketones into a,fi-unsaturated isocyanides, which can be hydrolyzed to the one-carbon homologated aldehyde. 

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