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This protocol proved particularly useful for preparation of monosubstituted allenes, which are
summarized in Table 2.1. These substrates were prepared in order to study the scope and
limitations of the Mo-mediated and Rh-catalyzed cyclocarbonylation reaction. Phenylalanine,
alanine and leucine derived allenes (58b, 58c and 58d, respectively) were prepared in yields
ranging from 40 to 95% for the Claisen rearrangement step. The broad variations in yield do not
reflect differences in reactivity, but rather, difficulties associated with purification of the
resulting allenes from triphenylphosphineoxide (Ph3PO), which is a byproduct in the reaction.
Initial experiments were performed utilizing a procedure where an aqueous workup of the
reaction mixture after the methanolysis step was followed directly by flash chromatography to
separate the product from Ph3PO. However, more polar allenes such as the alanine derived 58c
proved difficult to separate completely and thus lower yields were obtained (40%).
Table 2.1 Synthesis of monosubstituted allenes 58b-58h.
BzHN
R 1. PPh3, CCl4, Et3N, MeCN, rt
2. MeOH, HCl, rt.
1
O
O
MeO2C R
NHBz
1
R
BzHN
•
1
OH
O
OH
DCC, DMAP
CH2Cl2 54 56 58
Entry R 1 Ester/Yield% Allene/Yield% Entry R 1 Ester/Yield% Allene/Yield%
1 56b/98 58b/95
2 Me
56c/68 58c/40
3 56d/90 58d/62
OMe
4 56e/85 58e/70
S
NBoc
F
5 56f/42 58f/65
6 56g/52 58g/83
7 56h/66 58h/64 a
a Claisen rearrangement step was performed at 50 o C; MeOH, Et3N was used instead of MeOH, HCl to prevent Boc-removal.
In later experiments, it proved advantageous to circumvent the aqueous work-up, and precipitate
the solid Ph3PO by addition of hexanes to a solution of the crude reaction mixture in diethyl
ether. This was followed by chromatography of the filtrate after removal of the solvents under
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