Benzhydryl ethers diphenyldiazomethane

Besides the methods described above for the side-chain anchoring of Ser and Thr, the 3,4-dihydro-2//-pyran-2-functionalized-resin and handle 331 23,124] Table 3) allows the preparation of peptide alcohols by treatment with TEA in the presence of scavengers. Furthermore, the alkylation of Fmoc amino alcohols with a diphenyldiazomethane polymeric resin 34 gives rise to a benzhydryl ether, which can be cleaved with TFA/CH2CI2 (2 98) to give protected peptide alcohols. 

In the absence of acid, diphenyldiazomethane, or DDM as it is conveniently abbreviated, decomposes unimolecularly with the loss of nitrogen, either on heating or on irradiation. In alcoholic solutions in the presence of oxygen the products of both thermal and photochemical decompositions have heen well established as the benzhydryl ether of the solvent, diphenylketazine, tetraphenylethane and benzophenone (Bethell et al., 1965 Kirmse, 1963 Bartlett and Traylor, 1962). All of these products can be visualized as coming from a diphenylcarbene intermediate. 

Suggestive evidence for the protonation of diphenylcarbene was uncovered in 1963.10 Photolysis of diphenyldiazomethane in a methanolic solution of lithium azide produced benzhydryl methyl ether and benzhydryl azide in virtually the same ratio as that obtained by solvolysis of benzhydryl chloride. These results pointed to the diphenylcarbenium ion as an intermediate in the reaction of diphenylcarbene with methanol (Scheme 3). However, many researchers preferred to explain the O-H insertion reactions of diarylcarbenes in terms of electrophilic attack at oxygen (ylide mechanism),11 until the intervention of car-bocations was demonstrated by time-resolved spectroscopy (see Section III).12... 

Much kinetic work has been done on the reaction of diphenyldiazo-methane with weak acids, HA (mainly carboxylic acids), in ethanol or toluene solutions [214, 216]. In these studies, catalysis by solvated protons is negligible in ethanol and non-existent in toluene. The reaction is first-order in diphenyldiazomethane and first-order in weak acid, HA. Reaction products in ethanol are benzhydryl ethyl ether (Ph2 CHOEt) and benzhydryl ester (Ph2 CHA). The only product in toluene is benzhydryl ester. The product ratio of the reaction in ethanol is insensitive to the addition of salts of the weak acid, and it is almost independent of the chemical nature of HA [216]. The solvent isotope effect in the reaction with benzoic acid in ethanol is (fenAktoH/ Da)eiod = 3.5. 

The ambiguity concerning the significance of the observed hydrocarbon products extends to the products of reaction with the solvent. In hydroxylic solvents there are several examples of well-established carbenoid reactions leading to alcohols or ethers as products (Kirmse, 1963,1964 Bethelle aZ., 1965). The photolysis of diphenyldiazomethane in the presence of lithium azide in methanol leads to the same proportions of benzhydryl azide and benzhydryl methyl ether as does the solvolysis of benzhydryl chloride under the same conditions (Kirmse, 1963). 

The first step in the decomposition of nitrosoamides 123) is formation of the diazo ester 125) which fragments to a diazonium ion pair (128)129 The ion pairs thus produced differ from those obtained in the reaction of diazoalkanes with acids. The ratio of ester to ether formed in the decomposition of rV-nitroso-fV-benzhydrylbenz-amides in alcohol is lower than that found in the reaction of diphenyldiazomethane 132) with acids, and in the solvolysis of benzhydryl benzoate (I35)135,136 This effect has been attributed to the intervention of trans-diazo ester in the decomposition of 125) which leads to a greater distance between carbocation and carbox-ylate anion. In the diazoalkane reaction attack of the acid occurs at the electron-rich carbon atom to generate the carboxylate in the immediate vicinity of the incipient carbocation. 

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