CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

In general, aromatic aldehydes reacted comparatively at faster rates (entries 4-7,
Table III.1.5) than the aliphatic substrates. Benzylation of the chiral aldehyde 1 (entry 8,
Table III.1.5) also proceeded efficiently to produce the homobenzylic alcohol as a mixture
of syn (91a) and anti-isomers (91b) in good yield and syn selectivity [syn : anti ~ 80 : 20].
Owing to the inseparability of the diastereomers (91a/91b) by column chromatography,
their ratio could be assayed from 13 C NMR spectrum (Fig III.1.22) of this mixture. In
general, all the 13 C NMR peaks of 91a consistently appeared at more downfield compared
to the corresponding signals of anti-isomer 91b. This could be evident from the fact that
following oxidation of this isomeric mixture and syn-selective K-selectride ® reduction of the
diastereomeric mixture 91a and 91b, the downfield signals of syn-91a enhanced very much.
This will be further discussed in Chapter IV. This enabled us to determine the proportion
(91a:91b) in the diasterisomeric mixture of the benzylation product of 1.
According to literature precedence, 129 the predominant formation of syn-91a
suggested that the addition of the active organocopper reagent (Scheme III.1.9) proceeds
through α-chelate cyclic model. It is worth noting that addition of PhCH 2 MgBr was found
to produce a mixture of 91a and 91b in much lower yield (43.8%) and diastereoselectivity
(syn/anti = 35:65). Thus, the present protocol was much superior. Also, the Grignard
reaction was more anti-selective. This also supports our proposed stereochemical model;
as compared to PhCH2MgBr, the benzyl-Cu intermediate would follow a chelatecontrolled
path.
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