Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

OB0 ester. Moreover, the stereochemistry at the parbon appears to induce this effect
since the minor rotamer seems to be absent in the 2S,4R-Cbz-Glu(y-Me)(OMe)OBO ester
4.74 isomer (Figure 4.4 bottom) regardless of solvent. Since anti carbarnate rotamers are
more stable than syn rotamers, presumably the anti rotamer corresponds to the major
doublet at 6 1.26 ppm and the syn rotamer the minor doublet at 6 1.08 ppm. Some
intrinsic property present in ~S,~S-C~~-G~U('~LM~XOM~)(OM~)OBO
ester 4.73 is therefore
responsible for the observed rotamer. Intramolecular hydrogen bonding may stabilize the
conformation depicted in Figure 4.7b in which both the OB0 and methyl groups are
equatorial in the syn-2S,4S conformer whereas the syn02S,4R conformer has the methyl
group axial, perhaps sufficiently disfavoured to explain the absence of the syn-2S,4R
isomer in the 2S,4R-Cbz-Glu(y-Me)(OMe)OBO ester 4.14 'H-NMR spectrurn. Similar
seven-membered hydrogen bond interactions have ken shown to be responsible for the
configurational stability in sugar thioureas," N-(a-hydr~peroxyalkyl)arnides,~ and
macrocyclic polypeptides." Corey and Lee also recently discussed the importance of
hydrogen-bonding as an organizing element in the restriction of rotation leading to
enantioselectivity in many rea~tions.'~ Polar pro tic solvents should disrupt the propensity
of the 2S,4S-methyl denvative to intramolecular hydrogen bond which would be detected
in the 'H-NMR specûum, however, the rotamer doublet is observed with solvents such as
methanold. If this phenornenon is indeed due to intramolecular hydrogen bonding, the
seven-member hydrogen bond must be sufficiently strong to overcome the disniptive
nature of methanol-c4.