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attractive, since additional functionality is generated in the course of the reaction (a cross-
conjugated triene in this case). Surprisingly, there are only few examples of lactam formation via
cycloisomerization reactions, and are strictly limited to preparing γ-lactams. For example, in
1999, Lu reported a Pd(0)-catalyzed tandem cyclization/amination of dienyne 148 leading to α-
alkylidene-γ-lactam 149 (Scheme 3.23). 100 More recently, Zhang reported an enantioselective
Rh(I)-catalyzed cycloisomerization of amide-tethered enyne 150, affording γ-lactam 151 with
>99% ee. 101 Notably, both reports used a benzyl protected amide, and Zhang reported that
reaction did not proceed with the unprotected amide.
Scheme 3.23 Transition metal-catalyzed formation of γ-lactams.
O
Bn N
+ PhI +
H
N 10 mol% Pd(OAc) 2
20 mol% PPh 3
MeCN, 80 o C, 71%
148 149
Bn
N
O
150
[Rh(cod)Cl] 2, (R)-BINAP
AgSbF 6, rt, 91%, >99% ee
To test the feasibility of a Rh(I)-catalyzed formation of δ-lactam trienes, amide-tethered
allenynes 145a-145d were synthesized by Boc-deprotection of amine 65f to 152 followed by
coupling with alkynoic acids 153a-d (Scheme 3.24). The use of a DCC/DMAP coupling protocol
(conditions A) proved useful in preparing amides 145b and 145d in sufficient amounts for
testing the subsequent cycloisomerization reaction (~100 mg). Nevertheless, this protocol results
in formation of additional byproducts including dicyclohexylurea which made the purification
difficult, and the yields irreproducible. To circumvent this issue, an alternative protocol was
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Bn
Bn
N
O
N
O
(-)-151
Ph
N