New silicon-mediated ring expansion of n-sized conjugated cycloalkenones into homoallylic n+3 lactones

Article abstract of DOI:10.1016/S0040-4039(03)01308-X

Silicon nucleophilic β-addition to various 2-cycloalkenones, followed ultimately by mild and rapid α-alkylation of the corresponding cycloalkanone enolates using diverse epoxides and BF₃·OEt₂, produces useful γ-lactols and γ-hydroxyketones. Hypervalent iodine-promoted oxidative fragmentation then yields regiospecifically unsaturated, 3-atom ring expanded, 8-10 membered homoallylic lactones with good control of alkene geometry.

Full text of DOI:10.1016/S0040-4039(03)01308-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5407–5409
New silicon-mediated ring expansion of n-sized conjugated
cycloalkenones into homoallylic n+3 lactones
Mark A. Hatcher, Kristina Borstnik and Gary H. Posner*
Department of Chemistry, School of Arts and Sciences, The Johns Hopkins University, Baltimore, MD 21218, USA
Received 11 April 2003; revised 23 May 2003; accepted 26 May 2003
Abstract—Silicon nucleophilic b-addition to various 2-cycloalkenones, followed ultimately by mild and rapid a-alkylation of the
corresponding cycloalkanone enolates using diverse epoxides and BF ·OEt , produces useful g-lactols and g-hydroxyketones.
3
2
Hypervalent iodine-promoted oxidative fragmentation then yields regiospecifically unsaturated, 3-atom ring expanded, 8–10
membered homoallylic lactones with good control of alkene geometry. © 2003 Elsevier Science Ltd. All rights reserved.
1
,2
Pursuing our interest3 in opening of epoxides by
is stable at −20°C for several weeks and, therefore, that
can be used as a stock solution. Enol silyl ether cleav-
age with methyllithium produces the corresponding b-
silylenolate that rapidly opens monosubstituted
epoxides at −78°C in the presence of BF ·OEt (Scheme
,4
ketone enolate anions, we report here new methodol-
ogy for such reactions involving b-silylenolates.
HMPA-promoted Michael addition of trimethysilyl-
lithium to 2-cyclohexenone and in situ enolate O-silyl-
ation produces bis-silylated product 1 (Scheme 1) that
5
3
2
1).
Scheme 1.
*
Corresponding author.
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01308-X

5
408
M. A. Hatcher et al. / Tetrahedron Letters 44 (2003) 5407–5409
Several aspects of Scheme 1 are noteworthy. Direct
epoxide opening by the initial b-silylcyclohexanone eno-
late formed in the first step of Scheme 1 in the presence
of HMPA was not successful, due presumably to the
undesirable Lewis base–Lewis acid interaction between
ketone 4 (rather than the corresponding cyclized
1
hemiketal) (Scheme 1), as indicated by both H NMR
2
and IR spectroscopy. Although iodobenzene diacetate
and iodine failed to achieve oxidative fragmentation of
1
0
b-ketosilane 4, ceric ammonium nitrate (CAN) suc-
ceeds; at 0°C, a large excess of CAN produces trans-
homoallylic lactone 5-t in 83% yield, whereas at 85°C,
four equivalents of CAN produces cis-homoallylic lac-
6,7
HMPA and BF ·OEt . Oxidative fragmentation of
3
2
8
a
g-hydroxysilanes 2 with hypervalent iodobenzene di-
acetate and molecular iodine proceeded stereoselec-
tively in the absence of photochemical irradiation, pre-
8b
tone 5-c in 85% yield. Apparently, the CAN-promoted
8c
sumably via a hemiketal hypoiodite intermediate, to
11,12
formation of an intermediate b-silyl radical
that
provide cis-lactones 3 in high yields. The cis-geometry of
then forms an alkene double bond is subject to kinetic
or thermodynamic control, with formation of lactones
lactone 3a, for example, was confirmed by i-Bu AlH
2
reduction into the corresponding acyclic vicinally disub-
5
-t or 5-c, respectively.
1
stituted alkene showing a typical H NMR cis-double
9
bond H–H coupling constant of 10.8 Hz. The overall
yields of 48–52% from 2-cyclohexenone to 9-membered
cis-homoallylic lactones 3 compare favorably with our
previous results (31–52%) using environmentally less
1
desirable tin and lead chemistry that generates also
(1)
stereoselectively 9-membered, but isomeric, trans-
homoallylic lactones (Eq. (1)). In a control reaction,
iodobenzene diacetate and iodine did not cause isomer-
ization of such 9-membered trans-homoallylic lactones
into the thermodynamically more stable cis-isomers.
Both 5- and 7-membered conjugated cycloalkenones also
undergo this silicon-mediated 3-atom ring expan-
sion process (Schemes 2 and 3). Cyclopentenone-
b-Silylcyclohexanone enolate opening of cyclohexene
oxide, a 1,2-disubstituted epoxide, produces g-hydroxy-
Scheme 2.
Scheme 3.

M. A. Hatcher et al. / Tetrahedron Letters 44 (2003) 5407–5409
5409
derived b-silyl enol silyl ether 6 is stable at −20°C for
several days. Hemiketals 7 are rapidly formed via
BF ·OEt promoted opening of several monosubsti-
9. Niwa, H.; Wakamatsu, K.; Yamada, K. Tetrahedron
Lett. 1989, 30, 4543–4546.
10. (a) Trahanovsky, W. S.; Himstedt, A. L. J. Am. Chem.
Soc. 1974, 92, 7974–7976; (b) Wilson, S. R.; Zucker, P.
A.; Kim, C.-W.; Villa, C. A. Tetrahedron Lett. 1985, 26,
1969–1972.
11. Chatgilialoglu, C.; Schiesser, C. H. In The Chemistry of
Organic Silicon Compounds; Ruppaport, Z.; Apeloig, Y.,
Eds.; Silyl radicals; John Wiley: New York, NY, 2001;
Vol. 3.
3
2
tuted epoxides at −78°C. Iodobenzene diacetate and
iodine stereoselectively convert g-lactols 7 into 8-mem-
bered cis-homoallylic lactones 8 in 52–66% overall
yields (Scheme 2). Cycloheptenone-derived b-silyl enol
ether 9, like 6, is stable at −20°C for several days.
g-Lactols 10 are easily formed via BF ·OEt promoted
3
2
epoxide opening. Iodobenzene diacetate and iodine
transform g-lactols 10 into 10-membered homoallylic
lactones 11 as a 1:1 mixture of double bond geometric
isomers (Scheme 3). Reduction of the double bond in
1
1
1
2. Masterson, D. S.; Porter, N. A. Org. Lett. 2002, 4,
253–4356.
3. Suginome, H.; Yamada, S. Tetrahedron Lett. 1985, 26,
715–3718.
4
3
1
0-membered homoallylic lactols 11d produces fragrant
4. A typical gram-scale experimental protocol follows:
natural product (±)-phoracantholide (12) in four steps
and in 30% overall yield from 2-cycloheptenone.
1,13
Hemi-ketal 2a. To a 10 mL flask was added silylenol-
5
ether 1 (1.05 g, 4.33 mmol) and THF (6 mL). The
solution was cooled to 0°C and MeLi (2.78 mL, 4.43
In summary, using silicon and hypervalent iodine rather
than toxic tin and lead reagents allows 3-step 3-atom
ring expansion of 5–7 membered cycloalkenones into
more complex and thus more valuable 8–10 membered
homoallylic lactones on gram scale and in overall 36–
mmol, 1.60M in Et O) was added dropwise. After 10
2
min, the solution was cooled to −78°C and 4-phenyl-
butene oxide (0.320 g, 0.320 mL 2.16 mmol) was added
via syringe. The reaction was stirred for another 5 min at
−
78°C and BF ·Et O (0.275 mL, 2.16 mmol, neat) was
3 2
6
6% yields from stock solutions of bis-silylated interme-
14
added very slowly (1 drop/5 s), while cooling the needle
with a piece of dry ice. The reaction was quenched after
diates 1, 6, and 9. An unusual but reliable and useful
temperature effect was observed in the CAN-promoted
oxidative fragmentation of b-silylketones 4; low tem-
perature kinetic control generates trans-homoallylic lac-
tone 5-t, whereas high temperature thermodynamic
control produces the more stable cis-homoallylic lac-
tone 5-c. Study of the mechanism, the scope and limita-
tions, and some complex natural product applications
25 min with phosphate buffer (2 mL, pH 7.0) and
warmed to rt. The mixture was extracted with Et O (3×30
2
mL). The ether fractions were combined, dried over
MgSO4 and the solvent was removed under reduced
pressure. The remaining oil was purified by silica gel
chromatography (85% hexanes, 15% ethyl acetate, Et N
3
ꢀ
3%) to give desired hemi-ketal 2a (0.415 g) as a white
7
of these overall homologous Baeyer–Villiger reactions
1
solid (60% yield). Mp 91–92°C; H NMR (CDCl ) l
3
will be reported in a full article.
7
2
1
.30–7.26 (m, 2H), 7.21–7.18 (m, 3H), 4.24–4.17 (m, 1H),
.77–2.61 (m, 1H), 2.14–1.97 (m, 4H), 1.88–1.75 (m, 2H),
.68–1.54 (m, 5H), 1.43–1.34 (m, 1H), 1.09–1.99 (m, 1H),
13
Acknowledgements
0.59–0.51 (m, 1H), 0.01 (s, 9H); C NMR (CDCl
1
3
3
) l
42.04, 128.36, 128.30, 125.72, 105.26, 78.24, 44.82, 40.02,
7.25, 36.04, 32.57, 26.72 26.11, 24.33, −1.91; HRMS (CI)
+
m/z (M+Na) calcd. 341.1907 for C H O SiNa , found
We thank Johns Hopkins University and the NSF for
seed support of this project.
19 30
2
341.1894.
Lactone 3a. Hemi-ketal 2a (0.415 g, 1.303 mmol) was
placed in a 25 mL flask with CH Cl (8 mL, anhydrous)
2
2
and cooled to 0°C. To this was added PhI(OAc) (0.462
2
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7
8
13
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20 2