Isocyanides s. Isonitriles

H-3,1 -benzoxazin-4-ones, 2-amino- 24, 453 Isocyanides s. Isonitriles Isocyanurates, disubst. 

Of the four components reacting in the Ugi reaction, the isocyanide and the carboxylic acid have only limited influence on the overall stereoselection. For instance, in the synthesis of 13-demethyldysidenin (R)-l and 13-demethylisodysidenin (S)-l from a chiral aldehyde, chiral carboxylic acid, isonitrile and methylamine79. 

One of the pioneer works in the synthesis of DKPs through MCRs was reported by Hulme and coworkers in a three-step solution phase protocol based on UDC [33, 34]. They have obtained a series of different DKPs by reacting Armstrong s convertible isocyanide with aldehydes, M-Boc-protected amino acids as bifunctional acid component containing a protected internal amino nucleophile, and amines in methanol at room temperature. After Ugi-reaction, the isonitrile-derived amide is activated with acid (UAC) and allows cyclization to the DKP with the... 

Krasavin et al. described the synthesis of dihydropyrazol pyrazine diones via Ugi-4CR, employing ferf-butyl isocyanide as a convertible reagent [102], The authors reported that, under microwave irradiation, the ferf-butyl isocyanide behaves similar to Armstrong s isocyanide, furnishing the DKPs in good yields. It is noteworthy that the low priced isonitrile applied may be helpful for developing large-scale syntheses in the future (Scheme 6). 

Recently, a combination of the UAC and UDC protocols was reported by Wessjohann s group [40]. In this work, the acid-activated, well-behaved 1-iso-cyano-2-(2,2-dimethoxyethyl)-benzene was employed as convertible isocyanide in an Ugi-4CR [41]. The advantage of this one-pot procedure is the in situ deprotection of the W-protected amino acid along with the simultaneous activation of the isonitrile-bom carboxylate, enabling the nucleophilic attack of the free amine... 

The competition between mechanisms B and C has been invoked in order to explain the surprising inversion of diastereoselectivity achieved by a simple variation of the overall reactant concentration at low concentration (S)-19 prevails, while at high concentration (R)-19 is formed in greater amounts [22, 23], An increase in concentration of the isocyanide is indeed expected to favor mechanism B over C, because it accelerates the isonitrile attack, making it non-rate-limiting. The concentration of the other components has the same effect for all mechanisms. 

Curran s photocatalytically induced radical [4+1] annulation of phenyl isocyanide (13) and bromopyridone (14) represents the key step of the campto-thecin synthesis [80, 81]. The remarkable one-step synthesis of the tetracyclic heterocyclic system starts with photolytic cleavage of hexamethylditin to form the Me Sn radical, which then cleaves the C-Br bond in 14. This new radical reacts with the isonitrile carbon to form 15 which yields the final 16 via two subsequent radical intermediates (eq. (8)) (cascade or domino reaction [65, 66]). 

A stirred and cooled mixture of N-methylhydroxylamine hydrochloride, propion-aldehyde, and triethylamine in methanol treated with cyclohexyl isocyanide and allowed to stand at room temp, until the isonitrile odor has disappeared product. Y 75%. F. e. s. D. Moderhack, G. Zinner, and W. Heuer, Z. Chem. 15, 55 (1975) a-hydroxylaminocarboxylic acid amides cf. Arch. Pharm. 308, 321 (1975). 

Denmark has described several chiral bis-phosphoramides as Lewis base activators of weak Lewis acid SiCL and demonstrated their ability to mediate an enantioselective Passerini-type reaction. Catalytic bis-phosphoramide 36 and stoichiometric SiCU, in the presence of a proton scavenger (Htinig s base), promoted the formation of a-hydroxyamides with remarkably good enantioselectivity and yield. A variety of aromatic and unsaturated aldehydes and aryl, alkyl, and functionalized alkyl isocyanides proved to be useful and effective starting materials. High yields of Passerini products were attributed to the production of imidoyl chloride 37, which reduced the prevalence of the nitrilium intermediate and prevented the addition of a second equivalent of isonitrile. 

The use of phosgene in the presence of triethylamine has become an often applied method since Ugi s extensive works in this field [1157]. As a prelude to preparative isonitrile chemistry, Ugi s 1971 procedure for the production of tert-butyl isocyanide is presented [1165]. tert-Butyl formamide is dehydrated with phosgene to afford fert-butyl isocyanide in 82% yield. 

S. K. Guchait, C. Madaan, Org. Biomol. Chem. 2010, 8, 3631-3634. Towards molecular diversity dealkylation of tert-butyl amine in Ugi-type multicomponent reaction product establishes fcrt-butyl isocyanide as a useful convertible isonitrile. 

Equimolar mixtures of allyl isocyanide and benzaldehyde in toluene heated 12 hrs. at 80° under Ng in the presence of a catalytic amount of CU2O -> product. Y 95%. F. e., also J -pyrrolines from ethylene derivs. and isonitriles, s. T. Sae-gusa, I. Murase, and Y. Ito, Bull. Chem. Soc. Japan 45, 830 (1972). 

A mixture of phenylacetic acid, -butyl bromide, cuprous oxide, and cyclohexyl isocyanide as base in benzene stirred and heated 17 hrs. at 80° -> -butyl phenyl-acetate. Y 86%. - Pyridine may also be used as base but is less effective than isonitriles. F. e. s. T. Saegusa and I. Murase, Synth. Commun. 2, 1 (1972). 

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