NAS of Anhydrides by Oxomolybdenum Species
ylmethyl esters are similar in acid lability to tert-butyl
esters and can be readily cleaved under mild Brønsted
acids (e.g., HCl in CH3CN64), warmed organic acids (e.g.,
CF3CO2H, AcOH, and HCO2H) or by methanolic NaOH,
the current applications signify a handy approach toward
diphenylmethyl ester synthesis under mild reaction
conditions by using benzoic anhydride as the coupling
agent. In addition, pyruvates with chiral prosthetic
groups arising from secondary alcohols are useful sub-
strates for asymmetric synthesis, particularly in reduc-
tion, addition, and aldol reactions. Their syntheses by
direct couplings between pyruvic acid and appropriate
alcohols have been similarly achieved by several conven-
tional methods as just mentioned.65 The example as
illustrated in the case of 2b offers a powerful and mild
alternative for their syntheses. Notably, the mixed
anhydride approach by using benzoic anhydride in the
presence of catalytic MoO2Cl2 or V(O)(OTf)2 is unprec-
edented and all these demonstrations are so far un-
achievable by all the conventional (e.g., DMAP) and metal
triflate-based catalysts reported to date.
ized to amides,70 esters,71 and thio acids.72 The mixed-
anhydride technique was thus further applied to dipep-
tide73 (class III), tert-butylthio ester,74 and N-tert-
butylamide (class IV) syntheses, as illustrated in the
direct coupling of Fmoc-L-leucine with methyl L-tert-
leucinate, tert-butanethiol, and tert-butylamine in 90%,
96%, and 96% yields, respectively. Classical ways of
accessing these functional molecules from the corre-
sponding acids also require either initial stoichiometric
mixed-anhydride formation (e.g., with CF3(CO)2O75 or
ClCO2R70c,76) and subsequent reaction with the respective
nucleophile (a two-step procedure) or the use of a stoi-
chiometric coupling agent like DCC/EDC,77 (EtO)2P(O)-
CN,78 1,1′-carbonyldiimidazole,79 and PyBOP80 (a one-pot
procedure) in basic media. Furthermore, trityl methacryl-
ate (class V) can also be readily synthesized by combining
the mixed anhydride approach with the modified acyl-
ation protocol especially for tertiary alcohols at elevated
temperature. Conventionally, this substrate class can
only be made through a combination of trimethylsilyl
methacrylate and trityl fluoride or trityl silyl ether in
the presence of SiF4 or TMSOTf.81 The newly devised
recipe proves to be more handy and practical in terms of
large scale preparation. Notably, these five substrate
classes are important in view of their potential chiral
template82 (class I), combinatorial83 (class II), peptide84
(class II and III), medicinal85 (class II and IV, e.g., the
tert-Butylthio esters and N-tert-butylamides are popu-
lar derivatives of protected acids. The former compounds
can be unmasked by treatment with polymer-supported
SO3H,66a Br2/aq THF,66b or in aqueous LiOH/H2O2.67 The
later compounds can be readily unmasked in aqueous
acids (e.g., aqueous H2SO4 or 6 N HCl in protic solvents68
and TFA69) or bases (e.g., aqueous NaOH/EtOH69a). In
addition, tert-butylthio esters can be readily functional-
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