Download (3249Kb) - D-Scholarship@Pitt - University of Pittsburgh

eaction of butynyl-ester 176 (see experimental section for full details on the preparation of this
precursor). To our knowledge there are no reports of ester-tethered dieneyne participating in a
transition metal-catalyzed cycloaddition reaction, although ester-tethered enynes have been
shown to participate in a cycloisomerization reaction. 116 Interestingly, prolonged heating of
butynyl-ester 176 in presence of in situ generated catalytic Rh(I) ([Rh(dppe)Cl]2, AgSbF6, 1,2-
dichloroethane) resulted in formation of γ-lactone 178 in 78% yield (Scheme 3.36). The structure
of 178 was assigned based on the presence of a new olefinic resonance attributed to Hb in the
downfield region (at 7.14 ppm) displaying allylic coupling with the methyl group protons (q, J =
1.6 Hz). In addition to this, the presence of an amide was deduced based on a resonance in the 1 H
NMR as a broad singlet (at 6.39 ppm) and a broad amide stretching band for the N-H bond in the
IR (at 3344 cm -1 ). Compound 178 was rationalized to arise from Rh(I)-catalyzed
depropargylation of 176, followed by cyclization of the resulting carboxylic acid of 177 onto C4,
concomitant with allylic disposition of the C2 benzamide. This represents an overall 5-endo-trig
process known to be disfavored by Baldwin’s guidelines. 117
Scheme 3.36 Unexpected formation of γ-butenolide 178.
O
Bz
O
N
5
2 4
10 mol% [Rh(dppe)Cl] 2
20 mol% AgSbF 6
DCE, 95 o C, 12 h
78% of 178
O
Bz
OH
N
Bz
N
H
176 177 178
H c
H c
Bz
H b
H c
N H a
O
178
O
2
3
5
4
1 H NMR (in CDCl3):
H a 6.39 (bs, 1H)
H b 7.14 (q, J = 1.6 Hz, 1H)
H c 1.93 (d, J = 1.6 Hz, 3H)
IR: (N-H) 3344 cm -1
HRMS: C 18H 19NO 3 m/z [M] + 297.1379.
Since γ-lactones (butenolides) are important both as synthetic targets and intermediates, the
formation of 178 merited some further study. 118 To support the hypothesis that acid 177 is an
66
3
2
4
5
O
O