Isocyanates, addition isocyanides

The addition of isocyanides and azide to aldehyde-derived enamines has led to tetrazoles (533,536). On the other hand the vinylogous amide of acetoacetic ester and related compounds reacted with aldehydes, isocyanides and acids to give a-acylaminoamides (534). Iminopyrrolidones and imino-thiopyrrolidones were obtained from the addition of cyclohexylisocyanide and isocyanates or isothiocyanates to enamines (535). An interesting method for the formation of organophosphorus compounds is found in the reactions of imonium salts with dialkylphosphites (536). 

Isobutyl complexes, with Zr(IV) and Hf(IV), 4, 903—904 Isocyanates, lanthanide-catalyzed polymerization, 4, 152 Isocyanides bis-silylation, 10, 747 chalcogen-chalcogen additions, 10, 752 with chromium... 

One of the most facile methods for construction of the (i-lactam skeleton would be [2 + 2] cyclo additions of isocyanates to alkenes. However, the [2 + 2] cycloadditions of alkyl or aryl isocyanides with either 2,3-dihydrofuran or vinyl ethers often fails under normal conditions. High pressure can surmount this difficulty in certain cases. For instance, alkyl isocyanates 125 underwent [2 + 2] cycloadditions with such cyclic vinyl ethers as 126 to produce the P-lactams 127 (Scheme 34) [80]. 

Iron(1 +), dicarbonylethene(i]5-cyclopentadieny )- addition of carbon nucleophiles, 44 —, tricarbonyl(T -cyclohexadienyl)- addition of carbon nucleophiles, 44 Isobutyryl chloride, ot-acetoxy-, 160 3-Isochromanone, 1,4-dihydro-, 80 Isocyanates blocking of OH with, 301 Mocking of SH with, 229, 238 synthesis, 143, 301, 331 Isocyanides trapping of diallylnickel, 41 Isodrin pr., 192... 

A -Substituted (o-isocyanophenyl)acetamides (98), prepared by the addition of o-(lithiomethyl)phenyI isocyanide to isocyanates, are cyclized by CU2O catalyst to give indoles and/or l,3-benzodiazepin-4-ones (99) formation of the latter is favoured by less bulky R groups. " ... 

The addition of halogen to the C=S rather than the C—N bonds, as for example postulated by Gumpert for the bromination of phenyl isocyanate, is in line with the favored participation of the C=S bond in addition reactions of isothiocyanates One is tempted to speculate that the second step involves a-elimination of sulfur dichloride, followed by addition of chlorine to the generated isocyanide. However, further work is needed to establish the mechanism of this reaction. 

Besides this widespread pathway based on the intermediate N-acyliminium ion, several other established methods have been applied to construct the C5/C13 bond of the erythrinane skeleton. Thus, the Heck reaction has proved to be an attractive approach to the target compounds. The synthesis reported by Rigby (Scheme 10) starts with a smooth [1 -I- 4] cycloaddition of certain isocyanides to the vinyl isocyanate 79 affording the required hydroindolone 80. Then the iodoarene moiety has been installed by AT-alkylation with the phenethylmesylat 81 giving the N-alkylated precursor 82. Cyclization of 82 under Heck conditions yields the expected 7,8-dioxoerythrinane 83 as a single diastereomer, which then has been converted to ( )-2-cpi-erythrinitol (84) in twelve additional steps (64). 

As a replacement for alkynylanilines, Yamamoto has reported that indoles can he generated via the Pd(PPh3)4/CuCl-catalyzed coupling of 2-aIkynylaryUsocyanates with allylcarbonates (Scheme 6.18) [26]. In this case, fragmentation of the carbonate anion to an alkoxide upon oxidative addition to palladium allows conversion of the isocyanate into a carbamate for subsequent cydization. A number of substituted alkynes can participate in this reaction, and it can be performed with alcohols instead of allylcarbonates to form 3-unsubstituted indoles. A variant of this reaction involved the use of isocyanides in concert TMS-azide, providing a route to substituted N-cyanoindoles [27]. 

Reviews on the synthesis and chemistry of carbodiimides are given in [1248-1250]. Carbodiimides are mainly synthesized in one of three ways from ureas or thioureas, from isocyanates, or from isocyanides. Several reagents have been employed in carbodiimide synthesis phosgene [1252, 1253], dimethylphosgenimi-nium chloride [1254], tiiphosgene [561, 562], phosphorus pentoxide [1255], phos-phoryl chloride [1256], triphenylphosphine dibromide [758, 1257-1261], triphenylphosphine/tetrahalomethanes [1262, 1263], iminophosphoranes [1264-1277], Mitsunobu reagent [1278, 1279], p-tosyl chloride [1280, 1281], and CDC [1137] oxidative additions have also been used [1282-1284]. 

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