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The allenic amino acid derivatives obtained via these two methods appeared ideal for adapting to
the DOS strategy (both methods are discussed in detail in Section 2.2). Notably, the propargyl
esters are easily obtained in one step by coupling of the corresponding N-protected amino acid
and a propargyl alcohol, allowing for multiple points of diversity to be introduced. Therefore, the
allenic amino esters obtained in this manner were elected as pivotal intermediates for
development of a DOS strategy based on transition metal catalyzed cycloisomerization and
cyclocarbonylation reactions of allenes.
2.2.1 Synthesis of Allenic Amino Esters
2.2 Synthesis of the Pivotal Intermediates
2.2.1.1 Claisen Rearrangement via an Oxazole
The Claisen rearrangement of allyl and propargyl esters of α-amino-acids is a versatile
method for preparing unsaturated amino acid derivatives. This field was pioneered by Steglich in
the late 1970’s by demonstrating that N-benzoyl protected amino esters 51, under dehydrative
conditions (P2O5/CHCl3 or COCl2/pyridine), afford 4,4-disubstituted oxazolone derivatives 53
(Scheme 2.3). 58 The reaction involves an in situ formation and [3,3] sigmatropic rearrangement
of allyloxy-oxazole 52.
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