Copper complexes, regioselective protection

After the simultaneous protection at 04 and 06, the differentiation of the remaining 2-hydroxyl and 3-hydroxyl is puzzling for glucosides because they are both secondary and equatorial. Conditions reported in the literature usually result in mixtures of regioisomers [6], For example, the regioselective protection of diol 59 via a copper complex intermediate gave the 3-0-acylated derivatives 61 and 63 as the major products in moderate yields (Scheme 2.20) [172], Nonetheless, 2-0-benzoylation... 

Another methodology applied to the monosubstitution of diols is the use of copper complexation of dianions. The dianion is first formed by reaction of a diol with two equivalents of NaH. The copper complex is then formed by addition of a copper salt. Reaction of the copper complex with various electrophiles (alkyl halides, acyl chlorides) then gives the selectively protected products. As with the phase-transfer technique, very little disubstitution is observed. However, as illustrated in Scheme 3.16, the regioselectivity is reversed (i.e., 4,6-diols give mainly 4-substitution and 2,3-diols give mainly 3-substitution). Using this technique, both alkylations (benzylation, allylation) and acylations (acetylation, benzoylation, pivaloylation) have been carried out. As usual, the degree of selectivity depends on reaction conditions and structural factors [44]. 

SCHEME 3.16 Examples of regioselective protection from copper complexes. 

In this context, a one-pot regioselective protection of persilylated monosaccharides, using copper(ii) triflate as a single catalyst was able to promote acetalation-reductive etherification-acylation reactions. In the same way, the easy to handle, cheap and environment-friendly FeCls 6H2O complex was a very efficient catalyst to promote regioselective acetalation and reductive etherification on glucopyranosides. Hence, treatment of per-O-silylated a-methyl-u-glucopyranoside 50 with benzaldehyde (3 equiv) and triethylsilane (1.1 equiv) in the presence of... 

Regioselective introduction of protecting groups in lysine poses no major problem. The copper(II) complex of the amino acid is acylated and the N -acyl-derivative secured through decomposition of the complex, for instance with H S ... 

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