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the methyl ester and Ha are syn.
Scheme 4.34 Assignment of the relative stereochemistry of 287e and 288e based on NOESY
correlation spectrum.
Key NOESY crosspeaks of 287e and 288e:
Bz N
MeO2C H Hb H a
H c
O
H
Bz N
MeO2C H Hb H a
287e 288e
Similar observations collected from the reaction of the alanine-derived allenyne 74d led us to
postulate that in all cases where the R 1 is aliphatic, the product with the methyl ester and Ha in
syn orientation is obtained as the major diastereomer. u The facile isomerization of diastereomers
287d, 287e and 288b may be a result of the methyl ester carbonyl serving as an internal Lewis
base in labilizing the C-Ha bond as shown in Scheme 4.35.
Scheme 4.35 Ester assistance in the isomerization of 287e to 290e.
MeO
Ph
O
N
R
O
H
287e
H
O
MeO
Ph
O
N
R
δ
O
H
+
δ− H
O
H c
H
O
MeO
Ph
O
N
R
O
H
290e
It is noteworthy to mention that the α-alkylidene cyclopentenones 287a, 288a and 287c, 288c
(Schemes 4.30 and 4.32, respectively) did not isomerize under the silica gel conditions. In these
cases, the olefin is already tetrasubstituted and may account for this observation.
To rationalize the isomerization of only one cyclopentenone diastereomer, ab initio
energy calculations were performed comparing the energies of the phenylalanine-derived
u Another substrate derived from norvaline (R 1 = n-Bu) was shown to give the same diastereoselectivity as alanine
and leucine (personal communication from Dr. Stefan Fischer, Curran group).
109
O
H