Iodoamidation reaction

Towards this end, iodoamidation reactions were carried out on a variety of protected glucals tri-O-acetyl-D-glucal, tri-0-ben q l-D-glucal and tris-O-tert-butyldimethylsilyl-D-glucal (Scheme 1, 1) with several primary alkyl and aryl amides (32). The addition reactions of substituted ureas and protected amino acids were also investigated. 

A closely related procedure results in formation of y-lactoncs. Amides are converted to A -iodoamidcs by reaction with iodine and 1-butyl hypochlorite. Photolysis of the A -iodoamides gives lactones via iminolactone intermediates.209... 

The iodoamide 110 and iodoester 111 both cyclise to cyclopentanone, but to avoid further reaction in the case of the ester it was necessary to trap the tetrahedral intermediate with Me3SiCl. Six-membered rings formed from homologous starting materials only in very low yield.52... 

Accordingly, the iodoamidation of cyclohexene in acetonitrile was shown to result in quantitative yields. The chlorination of benzene derivatives [167] as well as the io-dination of anisole (mixture of the three isomers [168]) was also reported. However, these substitution reactions required very positive potentials, suggesting that the organic substrate has to be concomitantly oxidized. 

Et3B-induced additions of perfluoroalkyl iodides,7 a-iodo esters (Scheme 6.4), iodoamides,8 a-iodonitriles9 and simple alkyl iodides to alkenes and alkynes have been reported. Interestingly, these reactions were also performed with success in aqueous media,10 demonstrating the ability of Et3B to act as an initiator in water. 

Suarez developed neutral conditions for the Hofmann-Ldffler-Freytag reaction using a similar approach to the hypoiodite reaction described in Section 3.6.2.2. In this procedure, A -iodoamides are generated in situ by reaction of the corresponding amine derivative with iodine in the presence of lead tetraacetate or DIB as oxidizing agent. Nitroamines (Z = NO2) [67], phosphoramidates [Z = PO(OR)2 and PO(OEt)2] [68] and cyanamides (Z = CN) [69] have been used (Scheme 13, Eq. 13.1). A typical example is presented in Eq. (13.2). 

Intramolecular iodoamidation of pentenetriol derivative 52, obtained from L-threitol derivative 51, was used to prepare (-)-anisomycin in 17 20% overall yield (Scheme 6) [61]. Oxidation of 51 [62], followed by methylenation, acid hydrolysis, and protection with CCI3CN gave the olefin 52, whose reaction with iodine in the presence of sodium bicarbonate gave a 4.5 1 mixture of 53 and 54. Hydrolysis of the mixture, followed by N-protection with B0C2O afforded a 12 1 mixture of 55 and 56. On the other hand, when 52 was reacted with iodine monobromide in the presence of potassium carbonate, compound 53 only was obtained that could be transformed into a 37 1 mix-... 

As representative data in Table 1 shows, diastereomeric mbctures of gluco and manno iodoamides 2 9 were obtained from the reactions of these nitrogen nucleophiles with protected glucals. The major diastereomers observed in all cases, were the trans addition products, the a-manno and P-gluco isomers. 

Very closely related are two procedures that result in formation of y-lactones. In one procedure, amides are converted to iV-iodoamides by reaction with iodine and f-butyl hypochlorite. Photolysis of the N-iodoamides gives lactones via imino lactone intermediates ... 

The remote halogenation is believed to proceed by a chain mechanism analogous to the Hofmann-Loeffler reaction in both the iodoamide and bromoamide reactions. 

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