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

nucleophiles such as acetate and imidazole since hard nucleophiles such as amrnonia and
methoxide cause unwanted acyl-oxygen cleavage? No racemization is observed.
Scheme 1.29
@e
Nu = (CH&N. imidazole. NaOAc, NaSCH2Ph,
H2N-C(=S)-NHB HS(CH&NH2. &lgG Et8 O< = CI. Br)
= Me. Et. Ur, Mu, $Bu, Bu, Ph
Carbon-carbon bonds are fonned by reaction of the p-lactone 1.69 with
organocuprates since organolithiums and Grignard reagents lead to carbonyl attack. Di-
N-protected B-lactones were generaily found to be better substrates than the
corresponding mono-IV-protected B-lactones with yields in the range 70-80%, however,
the deprotected synthons also suffer from increased racemization (10-144 compared with
4% for mono-N-protected de ri vat ive^).^^
Threonine and other homologs canot be transfomed into p-lactones 1.70 under
Mitsunobu conditions although cyclization is successful using phenylsulfonarnide or 2-
nitrophenylsulfenyl amides with p-bromophenylsulfonyl chlonde in pyridine.
Unfortunately, the range of nucleophiles that add successfulIy to 1.70 is limiteci since
organometallic reagents add to the carbonyl. Those that do add, do so with inversion at
the Bcarbon (Scheme 1 .30).95