Synthesis of functionalised β-lactones via silylcarbocyclisation/desilylation reactions of propargyl alcohols

Article abstract of DOI:10.1016/j.tet.2009.10.112

Functionalised β-lactones were prepared starting from propargyl alcohols by means of an efficient rhodium-catalysed silylcarbocyclisation reaction. This process took place in high yields and complete stereoselectivity using DBU as the base, a sterically hindered alcohol and/or hydrosilane. Otherwise, a silylformylation competitive reaction occurred affording 3-hydroxy-2-[(aryldimethylsilyl)methylene]alkanals with complete regioselectivity. Indeed, while α-(aryldimethylsilylmethylene)-β-lactones were generated exclusively starting from an alkynol characterised by two alkyl groups on the propargyl carbon atom, significant amounts of the aldehydes were observed for secondary alcohols. In these cases, the use of ortho-substituted arylsilanes improved the chemoselectivity towards the α-methylene-β-lactones. Such molecules were then successfully converted into α-methylaryl-β-lactones by a fluoride-induced rearrangement of the aryl group that migrates from silicon to carbon with retention of configuration.

Full text of DOI:10.1016/j.tet.2009.10.112

Tetrahedron 66 (2010) 265–273
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of functionalised b-lactones via silylcarbocyclisation/desilylation
reactions of propargyl alcohols
*
Laura Antonella Aronica , Caterina Mazzoni, Anna Maria Caporusso
`
Dipartimento di Chimica e Chimica Industriale, Universita di Pisa, Via Risorgimento 35, 56126 Pisa, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2009
Received in revised form 9 October 2009
Accepted 29 October 2009
Available online 1 November 2009
Functionalised b-lactones were prepared starting from propargyl alcohols by means of an efficient rhodium-
catalysed silylcarbocyclisation reaction. This process took place in highyields and complete stereoselectivity
using DBU as the base, a sterically hindered alcohol and/or hydrosilane. Otherwise, a silylformylation
competitive reaction occurred affording 3-hydroxy-2-[(aryldimethylsilyl)methylene]alkanals with com-
plete regioselectivity. Indeed, while a-(aryldimethylsilylmethylene)-b-lactones were generated exclusively
starting from an alkynol characterised by two alkyl groups on the propargyl carbon atom, significant
amounts of the aldehydes were observed for secondary alcohols. In these cases, the use of ortho-substituted
Keywords:
Lactones
Silylformylation
Silylcarbocyclisation
Desilylation
arylsilanes improved the chemoselectivity towards the
successfully converted into -methylaryl- -lactones by a fluoride-induced rearrangement of the aryl group
that migrates from silicon to carbon with retention of configuration.
Ó 2009 Elsevier Ltd. All rights reserved.
a-methylene-b-lactones. Such molecules were then
a
b
1. Introduction
Considering the significant synthetic value of b-lactones, it is not
surprising that many synthetic methods have been developed to
achieve selective and efficient syntheses. The fundamental ap-
proaches for the preparation of 2-oxetanones are based on the lac-
b
-Lactones (2-oxetanones) have recently emerged as important
synthetic targets due to their occurrence in a variety of natural
compounds such as lipstatin, esterastin, valilactone, ebelactones,
anisatin and lupeolactone,1 which are efficient inhibitors of several
enzymes.2 Moreover, their utility as versatile organic intermediates
is well recognized since they combine the structural features of
a masked aldol product with the exceptional reactivity of a strained
ring system that may be readily opened by nucleophiles, undergo
enolate formation and reactions towards electrophiles. In addition
they can be transformed into unsaturated products by de-
carboxylation, undergo Lewis acid-promoted rearrangements
leading to ring expansion3 and polymerised by various initiators and
catalysts.4
tonization of
activations, lactonization of
Mukayama aldol-lactonization and [2þ2] cycloaddition of ketenes
and carbonyl compounds.5 Another attractive route to
-lactones is
b-hydroxyl acids via hydroxyl or carboxyl group
b-halocarboxylic acids, tandem
b
the ring-expansive carbonylation of epoxides, promoted by cobalt-
based catalysts.6 In 1990 Matsuda and co-workers7 reported the first
example of rhodium-catalysed silylcarbocyclisation of propargyl al-
cohols that generated
a-(triorganosilyl)methylene-b-lactones in
good yields, provided that a suitable base and a sterically hindered
hydrosilane were used (Scheme 1). In fact, silylformylation by-
products (i.e., b-silylalkenals), derived from the direct addition of CO
andsilanetothetriplebondwithoutcyclisation, wereoftenobserved.
R1
R2
t
R1
R1
SiMe2 Bu
R2
CO, base
HO
H
R2
C CH
+
t
BuMe2SiH
+
Rh4(CO)12
O
OH
t
CHO
SiMe2 Bu
O
silylcarbocyclisation
R1, R2 = H, Me,
(CH2)4, (CH2)5, (CH2)6.
silylformylation
product
product
Scheme 1.
The data described by Matsuda and further examples reported
by the author in a Japanese patent published in 1991,8 prompted us
to take into account the silylcarbocyclisation of several acetylenic
* Corresponding author. Tel.: þ39 0502219274; fax: þ39 0502219260.
E-mail address: aronica@dcci.unipi.it (L.A. Aronica).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.10.112

266
L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
alcohols with aryldimethylsilanes. We were particularly intrigued
by the possibility of applying the silylation-aryl migration protocol
that we had already developed for the synthesis of linear aldehydes
affording the corresponding 3-hydroxy-2-[(dimethylphenylsi-
lyl)methylene]alkanals 3 in good yields.
The reaction time was highly affected by the steric hindrance of
the alkyl and aromatic substituents on the propargyl carbon atom.
Indeed, when the steric requirements of the R2 group of the sub-
strates were increased from a hydrogen atom to an isobutyl group,
both the reaction time and the CO pressure had to be raised to gain
a nearly complete conversion of the reagents (Table 1, entries 1–3).
We determined that 30 atm of carbon monoxide and 24 h reaction
time were required for almost all the alcohols. Only in the case of
the most hindered 3,4,4-trimethyl-1-pentyn-3-ol 3g (Table 1, entry
7), the conversion reached 50% after four days, and the formation of
relevant amounts of hydrosilylation by-products was detected.
As described in Scheme 2, the silylformylation reaction pro-
ceeded with complete regioselectivity, i.e., the silicon moiety added
to the terminal carbon atom while the aldehydic group was in-
troduced into the internal position of the triple bond. The kineti-
cally favoured (Z)-3 isomers were principally formed together with
small amounts (4–21%) of the corresponding (E)-3 compounds. The
configuration of the two stereoisomers was confirmed by means of
NOESY experiments. For instance, in the cases of the carbonyl
compounds (Z)-3ea and (E)-3ea generated starting from 3-methyl-
1-pentyn-3-ol 1e, relevant NOE effects between the aldehydic
proton and the methyl groups bonded to the silicon atom were
detected in the (Z)-product as shown in Figure 1a; on the other
hand, the NOESY spectra confirmed the interaction between the
CHO proton and the vinyl hydrogen in the E-isomer (Fig. 1b).
and heterocycles9 to the preparation of functionalised
b
-lactones.
Indeed, we have shown that an aryldimethylsilyl moiety present on
-lactam or a -silylalkenal could act as carrier of the aryl group
a
b
b
from silicon to the adjacent carbon atom when tetrabutylammo-
nium fluoride was added. The two-step sequence of silylcarbocyc-
lisation–desilylation and aryl migration was applied to terminal
acetylenes containing functional groups in the
u-position such as
double and triple bonds, epoxide, esters, nitrile and hydroxyl. As far
as propargyl derivatives, while propargyl amides have been re-
cently10 employed in the synthesis of 2-benzylalkenals and 3-
methylaryl-b-lactams, in our opinion the reactivity of propargyl
alcohols as not yet been investigated comprehensively.
In this paper, we describe a detailed study on the silylformyla-
tion of several propargyl alcohols characterized by different steric
and electronic requirements. Subsequently, the silylcarbocyclisa-
tion process is considered and an analysis of the factors that can
influence the chemoselectivity of such reaction is reported. Finally,
the fluoride-induced aryl migration step will be extended to the
derivatives obtained.
2. Results and discussion
2.1. Silylformylation of propargyl alcohols
The silylformylation reactions of propargyl alcohols were per-
formed in a stainless steel autoclave charged with carbon monoxide
and an equivalent amount of the alcohol and the silane, in the
presence of 0.1% mmol of Rh4(CO)12. The results are summarised in
Table 1 and indicate that the substrates 1a–h (Scheme 2) selected
reacted readily with complete chemo- and regioselectivity,
Et Me
Et Me
HO
H
HO
SiMe2Ph
H
Ph
Me
O
Si
Me
O
H
H
a
(E)-3-ea
b
(Z)-3-ea
R2
R1
HO
H
(Z)-3
R1
Me PhSiH
2a
2
R1
R2
HO
C
1
CH
SiMe2Ph
R2
CHO
SiMe2Ph
CO,Rh4(CO)12
+
O
H
H
n
1a: H,H; 1b: H, Pr; 1c: H,
R2
HO
CHO
R1
c
O
H
i
Bu;1d: H, Ph, 1e: Me, Et;
SiMe2Ph
t
1f: (CH2)6; 1g: Me, Bu;
Figure 1.
H
(E)-3
1h: Me, Ph
Scheme 2.
It is well known that (Z)-silylalkenals can isomerise to the
E-structure in the presence of protic acids and high temperatures11,
but they have seldom been observed under the typical experi-
mental conditions of the silylformylation (10–30 atm CO, aprotic
solvent, room temperature). The unexpected E isomers could be
caused by the presence of the hydroxyl group that could favour an
s-trans conformation stabilized by a hydrogen bond between the
OH proton and the CO moiety (Fig. 1c). However, the increase of the
steric requirements of the propargyl substituents R1 and R2 de-
termined a reduction of stability of the E-geometry (Fig. 1c) and
consequently an improvement of the selectivity towards the Z
products as observed in entries 3 and 6–8 of Table 1.
Table 1
Silylformylations of propargyl alcohols with Me2PhSiHa
Entry
1
R1
R2
PCO
(atm)
t
(h)
Convb.
(%)
3
Yield (%)c
(Z)-3
(E)-3
1
2
3
4
5
a
b
c
d
e
H
H
H
H
H
10
10
30
30
20
12
24
24
24
24
100
99
80
100
86
aa
ba
ca
Da
ea
83(71)
84(53)
96(60)
79(66)
85(55)
17(11)
16(10)
4
21(12)
15(8)
nPr
iBu
Ph
Et
Me
6
f
30
24
100
fa
97(90)
3
2.2. Silylcarbocyclisation of propargyl alcohols
7
8
g
h
Me
Me
tBu
Ph
30
30
96
24
51
85
ga
ha
23(7)d
100(55)
d
d
The silylcarbocyclisation reactions were initially performed
under the experimental conditions (3 mmol silane, 3 mmol alcohol,
0.1 mol % Rh4(CO)12, 100 ꢀC, 4 h, 10% DBU), previously optimised for
a
Reaction conditions: 3 mmol of Me2PhSiH, 3 mmol of alcohol, 3.10ꢁ3 mmol of
Rh4(CO)12, 3 mL of CH2Cl2, room temperature.
b
Calculated by GLC conversion of the hydrosilane.
the synthesis of b
-lactams starting from propargyl tosyl amides.10
c
Determined by GLC and 1H NMR spectroscopic analysis of the reaction mixture
Contrary to what was observed for the silylformylation reaction,
the cyclisation process (Scheme 3) was favoured by a steric
after work up. In parentheses the isolated yields of pure compounds are reported.
d
Hydrosilylation by-products were detected by 1H NMR spectroscopy.

L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
267
environment around the propargyl carbon atom as shown in Table
2 (entries 3–5). In these examples the reactions were stereo-
selective yielding the (Z)-(dimethylphenylsilyl)methylene-b-lac-
tones 4ea–ga as almost sole products. An opposite behaviour was
observed in the reaction of 2-propyn-1-ol 1a giving exclusively the
containing hindered substituents (Scheme 4, Table 3, 2a–g).
While 2a–c and 2f are commercially available, o-tolyldime-
thylsilane 2d, p-phenylphenyldimethylsilane 2e13 and di-t-
butylphenylsilane 2g were easily prepared by reaction of the
t
corresponding chlorosilane R2ClSiH (R¼Me, Bu) with a suitable
corresponding
b
-silylalkenals (E, Z)-3aa together with small
Grignard reagent (ArMgBr, Ar¼o-tolyl, p-Ph-Ph, Ph). The data
listed in Table 3 clearly indicate that the choice of the silane plays
a crucial role in the silylcarbocyclisation process. In particular the
substitution of Me2PhSiH 2a with MePh2SiH 2b resulted in
a significant increase of the lactone yield from 36 to 50% (Table 3,
entries 1, 2). Unfortunately, more hindered phenylsilanes such as
2c and 2g were completely inactive (Table 3, entries 3, 8). When
p-phenyl-phenyldimethylsilane 2e was reacted with 1b the
complete consumption of the reagents was observed together
with a low chemoselectivity (Table 3, entry 6). Much better re-
sults were obtained in the reactions with o-tolyldimethylsilane
2d. Indeed, propargyl alcohols 1b and 1c were readily trans-
amounts of unidentified by-products. When a secondary propargyl
alcohol (1b) was tested, a slight improvement in the silylcarbo-
cyclisation process was detected (Table 2, entry 2, 36%
the major products still being aldehydes. Indeed, besides the
-silylalkenals (Z, E)-3ba, significant quantities (30%) of (Z)-2-
b-lactone),
b
[(dimethylphenylsilyl)methyl]-2-hexenal 5ba (Fig. 2) were identi-
fied by means of 1H NMR spectroscopic analysis.
R1
SiMe2Ph
R2
R1
4
R2
C CH
1
O
CO, DBU
formed into the corresponding b-lactones 4bd and 4cd (Table 3,
entries 4, 5) highlighting the importance of an ortho substituent
on the phenyl group bonded to the silicon atom.
O
+
R1
HO
R2
Rh4(CO)12
+
HO
H
Me2PhSiH 2a
CHO
SiMe2Ph
R1
SiR3
(Z, E)-3
H
R1
H
Scheme 3.
HO
H
O
R1
CO, DBU
Rh4(CO)12
R3SiH 2
O
4
+
H
C CH
CHO
SiR3
R1
SiR3
Table 2
Silylcarbocyclisation of propargyl alcohols with Me2PhSiHa
(Z, E)-3
HO
1
5
H
CHO
Entry
1
R1
R2
Conv.(%)b
3,4
Yield (%)c
4d
Scheme 4.
3 (Z/E)
1
2
3
a
b
e
H
H
Me
H
100
100
100
aa
ba
ea
0
70(66/34)e
29(46/54)f
7(100/0)
nPr
Et
36(24)
93(76)
Contrary to what was observed in the silylcarbocyclisation of
alkyl propargyl alcohols (vide supra), the reaction of 2-phenyl-3-
butyn-2-ol 1h with Me2PhSiH (Table 2, entry 6) did not afford any
lactone derivative but a complex mixture of products as depicted in
Scheme 5.
4
f
100
fa
99(85)
1(100/0)
5
6
g
h
Me
Me
tBu
Ph
99
85
ga
ha
96(85)
0
4(100/0)
8(100/0)g
The formation of 1-(dimethylphenylsilyl)-3-phenyl-1,2-butadi-
ene 6 can be ascribed to a thermal decarboxylation process of the
a
Reaction conditions: 3 mmol of Me2PhSiH, 3 mmol of alcohol, 0.3 mmol DBU,
3ꢂ10ꢁ3 mmol of Rh4(CO)12, 3 mL of CH2Cl2, 100 ꢀC, 4 h, 30 atm CO.
b
corresponding
b
-lactone 4ha. Indeed, it has already been demon-
Calculated by GLC conversion of the hydrosilane.
strated14 that
a
-alkylidene- -lactones can be converted into allenes
b
c
Determined by GLC and 1H NMR spectroscopic analysis of the reaction mixture
after work up.
via a [2þ2] cycloreversion mechanism (Scheme 5, step a), which is
favored by high temperature, polar solvents and electron donating
groups such as phenyl and vinyl. The decarboxylation reaction
generally takes place with complete retention of configuration of
d
In parentheses the isolated yields of pure compounds are reported.
e
Unidentified by-products were detected.
f
(Z)-3-[(dimethylphenylsilyl)methyl]-2-hexenal (30%) was detected by 1H NMR
spectroscopic analysis.
g
A complex mixture of several compounds was detected (Scheme 5).
the b-lactone substituents and has been applied to the synthesis of
polyfunctionalised allenes. After its formation, allene 6 may un-
dergo a prototropic rearrangement15, probably catalyzed by the
nPr
SiMe2Ph
CHO
base (DBU), thus generating dimethylphenylsilyl acetylene
7
(Scheme 5, step b). It is noteworthy that allenylsilanes are versatile
substrates, which have been shown to react efficiently with several
types of electrophiles.16
H
5ba
We tried to get the silylcarbocyclisation reaction of propargyl
alcohol 1h more chemoselective towards the corresponding
Figure 2.
b
-lactone acting on the experimental condition. Considering that
Matsuda and co-workers12 observed the formation of similar
products when they ran the silylformylation reaction of propargyl
amides with two equivalents of dimethylphenylsilane. The authors
demonstrated that 2-[(dimethylphenylsilyl)methyl]-2-alkenals
a polar solvent may favour the formation of the allene, a few re-
actions were performed using toluene instead of dichloromethane
(Table 4). A significant improvement in the yield of the lactone ring
was thus observed (Table 4, entry 2), although significant amounts
of by-products were still present in the reaction mixture. Sub-
sequently we investigated the influence of the temperature on the
reaction progress. When the temperature was lowered from 100 ꢀC
to 70 ꢀC, the allene by-product disappeared and the lactone resul-
ted nearly the sole product, even if a longer reaction time was
requested to achieve a high conversion of the reagents (Table 4,
entry 5). The results show that the silylcarbocyclisation reactions
derived from the interaction of b-silylalkenals with an extra mole of
silane. In the case of 1b, the lack of bulkiness of the propargyl
carbon probably reduces the rate of the silylcarbocyclisation re-
action favouring the silylformylation process and the subsequent
transformation of the resulting b-silylalkenals (Z, E)-3ba into 5ba.
In order to minimize the formation of the aldehydic by-
products, 1-hexyn-3-ol 1b was reacted with several arylsilanes

268
L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
Table 3
Silylcarbocyclisation of secondary propargyl alcohols with different hydrosilanesa
Entry
1
R1
2
R3SiH
Conv.(%)b
Yield (%)c
3–5
4d
3(Z/E)
5
1
2
3
4
5
6
7
8
b
b
b
b
c
b
b
b
nPr
nPr
nPr
nPr
iBu
nPr
nPr
nPr
a
b
c
d
d
e
f
Me2PhSiH
MePh2SiH
Ph3SiH
o-TolMe2SiH
o-TolMe2SiH
p-Ph-PhMe2SiH
tBuMe2SiH
tBu2PhSiH
100
100
0
100
98
100
80
0
ba
bb
bc
bd
cd
be
bf
36(24)
50(32)
d
29(46/54)
22(78/22)
d
30e
28
d
78(43)
81(53)
22(12)
66
22(100/0)
19(58/42)
22(36/64)
6(100/0)
d
d
d
37e
df
d
g
bg
d
a
Reaction conditions: 3 mmol of Me2PhSiH, 3 mmol of alcohol, 3.10ꢁ3 mmol of Rh4(CO)12, 0.3 mmol DBU, 3 mL of CH2Cl2, 30 atm CO, 100 ꢀC, 4 h.
Calculated by GLC conversion of the hydrosilane.
b
c
d
e
f
Determined by GLC and 1H NMR spectroscopic analysis of the reaction mixture after work up.
In parentheses the isolated yields of pure compounds are reported.
Unidentified aldehydic by-products were detected.
Several unidentified aldehydic by-products were detected by 1H NMR spectroscopic analysis together with small amounts of (E)-2-[(terbutyldimethylsilyl)methylene]-2-
hexanoic acid (9%).
Ph
O
CO2
SiMe2Ph
Ph
SiMe2Ph
Ph
SiMe2Ph
DBUH
Me
C
DBU
C
4ha 0%
Me
H
Me
b
a
O
6
66%
Ph
CO, DBU
Ph
Me
Me
C
CH
+
Me
HO
Ph
H
Rh4(CO)12
Me2PhSiH
100 °C
SiMe2Ph
HO
1h
Ph
Me
DBUH
SiMe2Ph
10%
CHO
SiMe2Ph
8%
(Z)-3ha
H
7
Scheme 5.
Table 4
lactones 4 were evaluated in the fluoride-mediated aryl migration-
desilylation process. The reactions were performed under very
mild experimental conditions, i.e., excess tetrabutylammonium
fluoride (2.5/1, TBAF) in THF, at room temperature.10 Un-
fortunately, when (Z)-3ba was tested as model compound,
2-benzylhexanal 8 was recovered as sole identified product, after
column chromatography on silica gel, in low yield (35%). Never-
theless, a complete conversion of the reagents was observed by
gas-chromatography (Scheme 6) together with the formation of
significant amounts of unidentified by-products. As already ob-
served for carboxylic esters and tosyl amides derivatives10, in this
case the 1,2-anionotropic rearrangement is coupled with an
elimination step, which generates double bonds with high
Silylcarbocyclisation of 2-phenyl-3-butyn-2-ol 1h with Me2PhSiH: temperature and
solvent effectsa
Entry
Solvent
T (ꢀC) t (h) Conv. (%)b Yield (%)c
4had
6d
66(41) 10 8e
7
(Z)-4ha
1
2
CH2Cl2
100
100
4
4
85
79
d
44
66
87
16
12
d
18 5e
11 10
CH3
3
4
80
70
4
4
80
42
CH3
CH3
d
13
n
Pr
OH
TBAF
THF
n
5
70
6
70
99 (53)
d
d
1
CH3
Pr
Ph
H
H
a
Reaction conditions: 3 mmol of Me2PhSiH, 3 mmol of alcohol, 3ꢂ10ꢁ3 mmol of
8
H
CHO
96/4
H2O
HO
100%
CHO
SiMe2Ph
Rh4(CO)12, 0.3 mmol DBU, 30 atm CO, 3 mL of solvent.
b
(Z)-3ba
Calculated by GLC conversion of the hydrosilane.
c
Determined by GLC and 1H NMR spectroscopic analysis of the reaction mixture
F
after work up.
d
In parentheses the isolated yields of pure compounds are reported.
Unidentified aldehydic by-products were detected.
n
Pr
e
OH
H
n
H
Pr
H
SiMe2F
Ph
CHO
SiMe2Ph
F
represent a versatile and direct method for the synthesis of
CHO
H
a
-alkylidene-b-lactones, useful building blocks generally obtained
by means of multi-steps sequences.17
n
Pr
n
OH
Pr
OH
H
H
H
SiMe2F
Ph
2.3. Fluoride promoted aryl migration reactions
The reactivity of 3-hydroxy-2-[(dimethylphenylsilyl)methyle-
Ph
SiMe2F
CHO
CHO
H
ne]alkanals (Z, E)-3 and (Z)-(aryldimethylsilyl)methylene-
b
-
Scheme 6.

L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
269
regioselectivity (96/4¼E/Z). The formation of 8 may be explained
considering the high affinity of silicon towards oxygen that can
transform OH in a good leaving group as described by the mech-
anism hypothesised in Scheme 6.
At this point, we investigated the transformation of silyl lactones
4 into the corresponding a-methylaryl-b-lactones via the aryl mi-
gration process promoted by fluoride ions (Scheme 7). The reactions
proceeded smoothly affording lactones 9 in good yields, as sum-
marized in Table 5. Only in the case of compound 9ha the purifi-
cation process needs to be optimized (Table 5, entry 4), probably due
to the ease of decomposition of the 3-benzyl-4-phenyl-4-methyl-
oxetan-2-one as previously observed for its precursor 4ha (see
Scheme 5 and Table 4). The reaction conducted with 4cd (Table 5,
entry 5) showed that the desilylation process was also successful for
It is noteworthy that the diastereoselectivity of the rearrange-
ment reaction depended on the steric requirements of the two
groups R1 and R2 of the propargyl carbon. Indeed, while the re-
action generated the main isomer in 70–90% yield for lactones 4ea
and 4cd (Table 5, entries 1 and 5), the selectivity was complete in
the cases of the more hindered substrates 4ga and 4ha (Table 5
entries 3, 4).
Finally, two homopropargylic alcohols, 5-hexyn-3-ol (10a) and
1-phenyl-3-butyn-1-ol (10b) were taken into account as model
substrates to be tested in the silylcarbocyclisation-desilylation and
aryl migration sequence (Scheme 8). As could be expected, both
steps proceeded smoothly, affording the corresponding g-lactones
11a,b and 12a,b in good yields (61–72%). Moreover, the TBAF-pro-
moted phenyl anionotropic rearrangement took place with a good
diastereoselectivity. NOESY experiments indicated the preferential
formation of the isomer characterized by the benzyl moiety in the
cis position respect to the R group. Preliminary results by molecular
mechanics analysis revealed a higher stability (ca. 4 Kcal/mol) of
the cis isomer respect to the corresponding trans isomer.
the b-lactone derived from a secondary propargyl alcohol (1c), and
that the aryl migration takes place with complete retention of the
configuration of the aryl group (i.e., o-tolyl).
R1
O
R1
SiMe2Ar
TBAF
Scheme 7.
Ar
R2
R2
3. Conclusions
O
4
9
O
O
In conclusion, according to Matsuda’s previous results, we have
shown that functionalised b-lactones can be accessed by a silylcar-
bocyclisation of propargyl alcohols with arylsilanes, which is fav-
oured by the presence of bulky substituents on both reagents.
Indeed, alcohols with two alkyl groups on the propargyl carbon
atom generated the corresponding (Z)-(dimethylphenylsilyl)-
Table 5
Fluoride promoted synthesis of
a
-arylmethyl-
Conv.(%)b
b
-lactones 9a
Entry
4
R1
R2
Ar
9
Yield (%)c Diastereomeric
ratio (trans/cis)b
methylene b-lactones in highyields with complete stereoselectivity.
1
2
ea Me Et
Ph
Ph
100
100
ea 66
fa 68
70/30
The presence on the acetylenic carbinol of a phenyl instead of an
alkyl group requested a simple optimisation process, i.e., the re-
placement of dichloromethane with toluene as solvent and the re-
duction of the temperature to 70 ꢀC. Analogously, monoalkylated
fa
d
3
4
5
ga Me tBu Ph
ha Me Ph Ph
cd
93
100
ga 59
ha 30
cd 60
100
100
89/11
propargyl alcohols were smoothly converted into b-lactones when
H
iBu o-Tol 100
bulky aryldimethylsilanes were employed. On the contrary, 2-pro-
pynol afforded exclusively the corresponding aldehydic products,
confirming the trend observed for the silylformylation process,
which takes place easily if poorly hindered alcohols are used. The
aryl migration step was then successfully applied to the (aryldi-
a
Reaction conditions: 2 mmol of lactones 4, 4.5 mmol of TBAF (1 M in THF), 15 mL
of THF.
b
Calculated by GLC and 1H NMR spectroscopic analyses.
Isolated yields of the major isomer are reported.
c
methylsilyl)methylene b-lactones. No ring opening was observed
and the aryl group was transferred from silicon to the adjacent
carbon atom with complete retention of configuration and with
The rearrangement process resulted highly diastereoselective
affording mainly
a-methylaryl-b-lactones 9 with the two bulky
substituents trans to each other. The configuration of the di-
astereomers was evaluated by means of NOESY spectra (Fig. 3). For
instance, in the case of 3-benzyl-4-ethyl-4-methyl-oxetan-2-one
9ea, significant NOE contacts between the benzyl protons and the
methyl group were observed.
high stereoselectivity, thus affording a-methylaryl-b-lactones use-
ful building blocks for organic synthesis18 and potentially valuable
as enzymes inhibitors.19 Finally, the process of cyclisation-aryl mi-
gration was extended to the preparation of
a-benzyl-g-lactones,
thus demonstrating the high versatility of the developed protocol.
R1
CH2 Ar
4. Experimental section
4.1. General remarks
R2
H
O
O
R1 = H, Me;
All solvents were reagent grade materials purified by standard
methods. THF was distilled from sodium, CH2Cl2 from P2O5 and
DBU from KOH immediately before use. All silanes 2 were distilled
and stored under inert gas. Non-commercial silanes 2d, 2e13 and 2g
9 ea-cd
R2 = Et, Bu, Bu, Ph, o-Tol
i
t
Figure 3.
30atm CO,
10% DBU
TBAF
100%
Ph
SiMe2Ph
OH
+ Me2PhSiH
R
R
O
R
O
Rh4(CO)12 (0.1%)
CH2Cl2, 100 °C, 4h
O
O
10a: R = Et
10b: R = Ph
100%
11a, R = Et, 64%
11b, R = Ph, 72%
12a, R = Et, 61%, cis/trans = 62/38
12b, R = Ph, 72%, cis/trans = 84/16
Scheme 8.

270
L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
were prepared from the corresponding Grignard reagents accord-
ing to the method described by Hiyama and co-workers.20 Prop-
argyl alcohols 1a–h were purchased from Sigma–Aldrich and
distilled before use. TBAF solution (1 M in THF) was purchased from
Fluka and used without purification. Rh4(CO)12 was prepared and
purified as previously reported.21 1H NMR (300 MHz) and 13C NMR
(75 MHz) spectra were recorded in CDCl3 solution with Me4Si or
silica gel using hexane/Et2O¼70/30 as eluent (10% yield); 1H NMR
d
0.50 (3H, s), 0.53 (3H, s), 0.80 (3H, t, J¼7.0 Hz), 1.00–1.70 (4H, m),
2.64–2.69 (1H, d, J¼9.5 Hz), 4.30–4.40 (1H, m), 6.81 (1H, s), 7.36–
7.40 (3H, m), 7.51–7.56 (2H, m), 9.42 (1H, d, J¼1.8 Hz); 13C NMR
d
ꢁ1.7, ꢁ1.3, 13.7, 19.1, 38.7, 71.8, 128.1, 129.6, 133.6, 137.1, 152.8,
158.0, 196.6; MS (EI) m/z (rel int.%): 244 (Mþ-18, 3); 169 (13); 155
(12); 141 (38); 135 (34); 129 (14); 113 (11); 105 (18); 93 (13); 91
CHCl3 as internal standards;
d
values are given in ppm and coupling
(20); 77 (58); 75 (100); IR n 3444, 3055, 2955, 2722, 1955, 1894,
constants (J) in Hertz. The Z/E and cis/trans configurations were
determined by means of NOE experiments. Infrared absorption
spectra were recorded as neat films. Mass spectra were obtained
with a Varian Saturn connected to a Varian 3800 gas chromato-
graph. GLC analyses were performed with a Perkin Elmer Clarus
1822, 1761, 1677, 1594, 1422, 1250.
4.2.5. (Z)-2-[(Dimethylphenylsilyl)methylene]-3-hydroxy-5-methyl-
hexanal (Z)-3ca. The crude oil was purified by column chroma-
tography on silica gel using CH2Cl2 as eluent (60% yield); 1H NMR
500 (30 mꢂ0.52 mm, 5
m
m) using He as the carrier gas and a flame
d
0.54 (6H, s), 0.93–0.98 (6H, m), 1.35–1.55 (2H, m), 1.75–1.89 (1H,
m), 2.41 (1H, sb), 7.19 (1H, s), 7.36–7.40 (3H, m), 7.52–7.55 (2H, m),
9.80 (1H, s); 13C NMR
ꢁ0.1, 21.9, 23.7, 25.1, 46.1, 70.2, 128.5, 129.9,
133.8, 137.7, 148.7, 158.6, 193.6; IR 3425, 3054, 2955, 1955, 1882,
ionization detector (FID). Column chromatography was performed
on silica gel 60 (230–400 mesh). All products were identified and
characterized by spectroscopic and analytical data.
d
n
1815, 1680, 1595, 1428, 1252. Anal. Calcd for C16H24O2Si: C, 69.51; H,
8.75; found: C, 69.58; H, 8.72.
4.2. General procedure for the silylformylation of propargyl
alcohols with aryldimethylsilanes catalyzed by Rh4(CO)12
4.2.6. (Z)-2-[(Dimethylphenylsilyl)methylene]-3-hydroxy-3-phenyl-
propanal (Z)-3da. The crude oil was purified by column chroma-
tography on silica gel using CH2Cl2 as eluent (66% yield); 1H NMR
Catalytic runs were performed in a 25 mL stainless steel autoclave
fitted with a Teflon inner crucible and a stirring bar. In a typical run,
freshly distilled CH2Cl2 (3 mL), previously degassed ArMe2SiH
(3 mmol), the required propargyl alcohol (3 mmol), and
3ꢂ10ꢁ3 mmol of Rh4(CO)12 were put, under CO atmosphere, in
a Pyrex ‘Schlenk’ tube. This solution was introduced in the autoclave,
previously placed under vacuum (0.1 mm Hg), by a steel syphon. The
reactor was pressurized with carbon monoxide and the mixture was
stirred at room temperature for the requested time. After removal of
excess CO (fume hood), the reaction mixturewasdiluted with CH2Cl2,
filtered on Celite and concentrated in vacuum. The reagents con-
version and the products composition were determined by GLC and
1H NMR. The purification of the crude oil by column chromatography
d
0.71 (3H, s), 0.73 (3H, s), 2.78 (1H, sb), 5.79 (1H, s), 7.39–7.72 (11H,
m), 9.94 (1H, s); 13C NMR
dꢁ0.4, 72.9, 126.6, 127.8, 128.2, 128.4,
129.6, 133.5, 137.3, 141.4, 148.8, 156.6, 192.7; MS (EI) m/z (rel int.%):
281 (Mþ-15, 12), 217 (15), 203 (88), 165 (29), 135 (66), 115 (24), 103
(36), 75 (100); IR
n 3433, 3055, 2955, 2722, 1950, 1877, 1822, 1760,
1678, 1586, 1422, 1250. Anal. Calcd for C18H20O2Si: C, 72.93; H, 6.80;
found: C, 73.24; H, 6.71.
4.2.7. (E)-2-[(Dimethylphenylsilyl)methylene]-3-hydroxy-3-phenyl-
propanal (E)-3da. The crude oil was purified by column chroma-
tography on silica gel using CH2Cl2 as eluent (12% yield); 1H NMR
on silica gel afforded the pure
b
-silylalkenals.
d
0.54 (3H, s), 0.55 (3H, s), 3.27 (1H, d, J¼9 Hz), 5.55 (1H, d, J¼9 Hz),
7.06 (1H, s), 7.22–7.65 (11H, m); 9.46 (1H, d, J¼1 Hz); 13C NMR
4.2.1. (Z)-2-Hydroxymethyl-3-[(dimethylphenylsilyl)methylene]pro-
panal (Z)-3aa. The crude oil was purified by column chromatogra-
phy on silica gel using hexane/AcOEt¼90/10 as eluent (71% yield); 1H
d
ꢁ1.4, 73.0,126.0,127.4,128.2,128.3,129.7,133.8,136.9,141.4,153.6,
156.0, 196.0; MS (EI) m/z (rel int.%): 281 (Mþ-15, 2), 217 (45), 203
(17),135 (49),115 (28),105 (28), 91 (19), 77 (48), 75 (100); IR 3444,
n
NMR
d
0.52 (6H, s), 2.00 (1H, sb), 4.35 (2H, d, J¼1.4 Hz), 7.17 (1H, t,
3066, 2944, 2722, 1950, 1877, 1822, 1760, 1683, 1600, 1422, 1250.
J¼1.4 Hz), 7.34–7.38 (3H, m), 7.49–7.53 (2H, m), 9.78 (1H, s); 13C NMR
d
ꢁ0.2, 64.7, 128.8, 130.2, 134.1, 137.8, 140.5, 144.8, 193.8; IR
n
3422,
4.2.8. (Z)-2-[(Dimethylphenylsilyl)-methylene]-3-hydroxy-3-methyl-
pentanal (Z)-3ea. The crude oil was purified by column chroma-
tography on silica gel using hexane/AcOEt¼80/20 as eluent (55%
3066, 2955, 2700, 1950, 1885, 1811, 1677, 1422, 1250. Anal. Calcd for
C12H16O2Si: C, 65.41; H, 7.32; found: C, 65.45; H, 7.30.
yield); 1H NMR
d
0.51 (6H, s), 0.80 (3H, t, J¼7.3 Hz),1.38 (3H, s),1.62–
4.2.2. (E)-2-Hydroxymethyl-3-[(dimethylphenylsilyl)methylene]pro-
panal (E)-3aa. The crude oil was purified by column chromatog-
raphy on silica gel using hexane/AcOEt¼90/10 as eluent (11% yield);
1.90 (2H, m), 3.19 (1H, s), 7.21 (1H, s), 7.32–7.37 (3H, m), 7.47–7.52
(2H, m), 9.79 (1H, s); 13C NMR
d
ꢁ0.3, 8.3, 26.6, 33.7, 75.5, 128.1,
129.4, 133.4, 137.6, 149.4, 159.6, 193.9; MS (EI) m/z (rel int.%): 247
(Mþ-15, 32), 229 (100), 185 (25), 169 (39), 167 (47), 165 (50), 155
(51), 145 (45), 137 (46), 135 (88), 121 (21), 103 (41), 91(22), 75 (39);
1H NMR
d
0.49 (6H, s), 2.40 (1H, sb), 4.38 (2H, d, J¼1.8 Hz), 7.24 (1H,
t, J¼0.7 Hz), 7.34–7.38 (3H, m), 7.49–7.53 (2H, m), 9.74 (1H, s); IR
n
3422, 3066, 2955, 2700, 1950, 1885, 1811, 1677, 1422, 1250.
IR n 3444, 3056, 2967, 2744, 1950, 1889, 1817, 1761, 1678, 1422, 1250.
Anal. Calcd for C15H22O2Si: C, 68.65; H, 8.45; found: C, 68.71; H, 8.38.
4.2.3. (Z)-2-[(Dimethylphenylsilyl)methylene]-3-hydroxy-hexanal
(Z)-3ba. The crude oil was purified by column chromatography on
silica gel using hexane/Et2O¼70/30 as eluent (53% yield); 1H NMR
4.2.9. (E)-2-[(Dimethylphenylsilyl)-methylene]-3-hydroxy-3-methyl-
pentanal (E)-3ea. The crude oil was purified by column chroma-
tography on silica gel using hexane/AcOEt¼80/20 as eluent (8%
d
0.51 (6H, s), 0.91 (3H, t, J¼7.1 Hz), 1.20–1.70 (4H, m), 2.40 (1H, sb),
4.50 (1H, m), 7.16 (1H, s), 7.30–7.45 (3H, m), 7.47–7.60 (2H, m), 9.77
yield); 1H NMR
d
0.51 (6H, s), 0.58 (3H, t, J¼7.2 Hz), 1.29 (3H, s), 1.42
(1H, s); 13C NMR
d
ꢁ0.3, 13.9, 18.9, 38.3, 71.2, 128.2, 129.6, 133.5,
(1H, s), 1.46–2.03 (2H, m), 6.86 (1H, s), 7.32–7.37 (3H, m), 7.50–7.56
137.5, 148.6, 158.0, 193.3; MS (EI) m/z (rel int.%): 247 (Mþ-15, 15),
(2H, m), 9.51 (1H, s); 13C NMR
d 0.0, 7.7, 27.7, 32.6, 75.5, 128.1, 128.9,
219 (13), 205 (24), 185(11), 141 (19), 135 (23), 129 (13), 105 (13), 91
133.2, 140.4, 155.5, 162.3, 194.8; MS (EI) m/z (rel int.%): 247 (Mþ-15,
(12), 75 (100), 43 (29); IR
n
3422, 3055, 2955, 2722, 1955, 1894,
32), 229 (100), 185 (25), 169 (39), 167 (47), 165 (50), 155 (51), 145
1822, 1761, 1677, 1586, 1422, 1250. Anal. Calcd for C15H22O2Si: C,
68.65; H, 8.45; found: C, 68.94; H, 8.37.
(45),137 (46), 135 (88),121 (21),103 (41), 91 (22), 75 (39); IR
3056, 2956, 2722, 1955, 1895, 1823, 1684, 1422, 1250.
n 3456,
4.2.4. (E)-2-[(Dimethylphenylsilyl)methylene]-3-hydroxy-hexanal
4.2.10. (Z)-2-[(Dimethylphenylsilyl)-methylene]-2-(1-hydroxy-cyclo-
(E)-3ba. The crude oil was purified by column chromatography on
hexyl)-propenal (Z)-3fa. The crude oil was purified by column

L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
271
chromatography on silica gel using CH2Cl2 as eluent (90% yield); 1H
NMR 0.49 (6H, s), 1.50–1.75 (10H, m), 2.87 (1H, s), 7.15 (1H, s),
7.39–7.51 (5H, m), 9.79 (1H, s); 13C NMR
1455, 1422, 1250, 1249, 1114. Anal. Calcd for C15H20O2Si: C, 69.19; H,
7.74; found C, 69.37; H, 7.81.
d
d
ꢁ0.3, 21.5, 25.5, 36.1, 73.7,
128.2, 129.5, 133.5, 137.6, 147.9, 161.2, 194.8; MS (EI) m/z (rel int.%):
4.3.3. (Z)-3-[(Dimethylphenylsilyl)-methylene]-1-oxa-spi-
ro[3.5]nonan-2-one (Z)-4fa. The crude oil was purified by column
chromatography on silica gel using hexane/Et2O¼70/30 as eluent
255 (Mþ-33, 17), 193 (11), 167 (11), 145 (10), 135 (44), 119 (15), 105
(22), 91 (30), 75 (100), 61 (15); IR
n 3444, 3055, 2922, 2733, 1843,
1887, 1816, 1766, 1677, 1422, 1250. Anal. Calcd for C17H24O2Si: C,
70.78; H, 8.39; found: C, 70.83; H, 8.41.
(76% yield); 1H NMR
d 0.54 (6H, s), 1.55–1.84 (10H, m), 6.22 (1H, s),
7.36–7.39 (3H, m), 7.55–7.59 (2H, m); 13C NMR
d 22.6, 24.2, 34.3,
87.1, 128.0, 129.5, 133.6, 137.0, 132.9, 156.7, 164.1; MS (EI) m/z (rel
4.2.11. (Z)-2-[(Dimethylphenylsilyl)-methylene]-3-hydroxy-3,4,4-tri-
methyl-pentanal (Z)-3ga. The crude oil was purified by column
chromatography on silica gel using CH2Cl2 as eluent (7% yield); 1H
int.%): 242 (Mþ-44, 10), 277 (5), 145 (14), 136 (17), 135 (100), 107
(12), 105 (15); IR
n 3055, 2938, 1800, 1444, 1422, 1255, 1111. Anal.
Calcd for C17H22O2Si: C, 71.28; H, 7.74; found: C, 70.97; H, 7.65.
NMR
s), 7.31–7.52 (5H, m), 9.75 (1H, s); MS (EI) m/z (rel int.%): 273 (Mþ-
15, 81), 231 (29), 211 (100),195 (20),145 (30),135 (80),105 (34); IR
3467, 3055, 2955, 2710, 1955, 1877, 1811, 1666, 1422, 1250. Anal.
Calcd for C17H26O2Si: C, 70.29; H, 9.02; found: C, 69.90; H, 8.93.
d 0.51 (6H, s), 0.89 (9H, s), 1.38 (3H, Hc), 1.62 (1H, s), 7.02 (1H,
4.3.4. (Z)-4-tert-Butyl-3-[(dimethyl-phenyl-silyl)-methylene]-4-
methyl-oxetan-2-one (Z)-4ga. The crude oil was purified by column
chromatography on silica gel using hexane/Et2O¼70/30 as eluent
n
(85% yield); 1H NMR
d 0.55 (6H, s), 1.01 (9H, s), 1.53 (3H, s), 6.18 (1H,
s), 7.35 (3H, m), 7.55 (2H, m); 13C NMR
d 2.3,19.6, 25.0, 36.6, 91.6,
4.2.12. (Z)-2-[(Dimethyl-phenyl-silyl)-methylene]-3-hydroxy-3-phe-
nyl-butanal (Z)-3ha. The crude oil was purified by column chro-
matography on silica gel using CH2Cl2 as eluent (55% yield); 1H
128.0, 129.5, 133.6, 133.8, 137.1, 155.8, 164.2; MS (EI) m/z (rel int.%):
273 (Mþ-15, 81), 231 (29), 211 (100),195 (20),145 (30),135 (80),105
(34); IR
n 3066, 2967, 1806, 1450, 1428, 1250, 1111. Anal. Calcd for
NMR
d
0.56 (6H, s), 1.65 (3H, s), 4.06 (1H, sb), 7.24–7.72 (11H, m),
C17H24O2Si: C, 70.78; H, 8.39; found C, 71.11, H, 8.47.
9.70 (1H, s); 13C NMR
d
ꢁ0.4, 29.1, 76.9, 124.6, 127.0, 128.2, 128.3,
129.7, 133.5, 137.3, 146.1, 148.8, 158.7, 194.4; MS (EI) m/z (rel int.%):
4.3.5. (Z)-3-[(Methyldiphenylsilyl)-methylene]-4-propyl-oxetan-2-
one (Z)-4bb. The crude oil was purified by column chromatography
on silica gel using hexane/Et2O¼70/30 as eluent (32% yield); 1H
295 (Mþ-15, 9), 217 (22), 199 (18), 165 (34), 141 (20), 103 (33), 91
(11), 75 (67), 135 (100); IR
1811, 1760, 1678, 1583, 1427, 1256. Anal. Calcd for C19H22O2Si: C,
73.50; H, 7.14; found: C, 73.17, H, 7.22.
n 3455, 3056, 2977, 2733, 1950, 1883,
NMR
d
0.59 (6H, s), 0.98 (3H, t, J¼7.8 Hz), 1.42–1.59 (2H, m), 1.74–
1.86 (2H, m), 4.84 (1H, t, J¼6.6 Hz), 6.29 (1H, s), 7.34–7.42 (3H, m),
7.58–7.61 (2H, m); MS (EI) m/z (rel int.%): 322 (Mþ, 10), 321 (27),
303 (39), 245 (24), 207 (54), 197 (100), 181(27), 145 (31), 137 (63),
4.3. General procedure for the silylcarbocyclisation of
propargyl alcohols with hydrosilanes catalyzed by Rh4(CO)12
129 (29), 105 (89), 77 (19), 53 (58). IR n 3066, 2944, 1889, 1811, 1461,
1422, 1250, 1107. Anal. Calcd for C20H22O2Si: C, 74.49; H, 6.88;
found: C, 74.43; H, 6.90.
Catalytic runs were performed in a 25 mL stainless steel auto-
clave fitted with a Teflon inner crucible and a stirring bar. In a typical
run, 3 mmol of alcohol, 3 mL of a freshly distilled solvent, 3 mmol of
R3SiH, 0.3 mmol of DBU and 3ꢂ10ꢁ3 mmol of Rh4(CO)12 were put,
via syringe and under CO atmosphere, in a Pyrex Schlenk tube. This
solution was introduced in the autoclave, previously placed under
vacuum (0.1 mmHg), by a steel syphon. The reactor was pressurised
to 30 atm of CO and stirred at 100 ꢀC for 4 h. The autoclave was then
cooled to room temperature and the excess of CO was removed
under fume hood. The reaction mixture was diluted with CH2Cl2,
filtered on silica gel and concentrated under reduced pressure. The
reagents conversion and the products composition were de-
termined by GLC and 1H NMR. The purification of the crude oil by
4.3.6. (Z)-3-[(Dimethyl-o-tolyl-silyl)-methylene]-4-propyl-oxetan-2-
one (Z)-4bd. The crude oil was purified by column chromatography
on silica gel using hexane/Et2O¼90/10 as eluent (43% yield); 1H
NMR
d
0.75 (3H, s), 0.74 (3H, s), 1.15 (3H, t, J¼7.4 Hz), 1.28–1.54 (2H,
m), 1.76–1.87 (2H, m), 2.57 (3H, s), 4.86 (1H, dt, J¼7, 1 Hz), 6.33 (1H,
d, J¼1 Hz), 7.14–7.56 (4H, m); 13C NMR
d 1.5, 13.7, 17.9, 23.0, 35.3,
79.8, 124.6, 125.1, 129.4, 129.7, 133.9, 134.6, 143.0, 152.3, 163.6; MS
(EI) m/z (rel int.%): 259 (Mþ-15, 21), 231 (64), 183 (85), 159 (69), 149
(90),121 (51),115 (46), 91 (100), 75 (78); IR n 3044, 2944,1811,1460,
1283, 1250, 1127. Anal. Calcd for C16H22O2Si: C, 70.03; H, 8.08;
found: C, 70.19; H, 8.01.
column chromatography on silica gel afforded the pure b-lactones.
4.3.7. (Z)-3-[(Dimethyl-o-tolyl-silyl)-methylene]-4-isobutyl-oxetan-
2-one (Z)-4cd. The crude oil was purified by column chromatog-
raphy on silica gel using hexane/Et2O¼80/20 as eluent (53% yield);
4.3.1. (Z)-3-[(Dimethylphenylsilyl)-methylene]-4-propyl-oxetan-2-
one (Z)-4ba. The crude oil was purified by column chromatography
on silica gel using hexane/Et2O¼90/10 as eluent (24% yield); 1H
1H NMR
d
0.62 (6H, s), 1.00 (6H, d, J¼6.6 Hz), 1.61–1.74 (2H, m),
NMR
d
0.59 (6H, s), 0.98 (3H, t, J¼7.8 Hz), 1.42–1.59 (2H, m), 1.74–
1.78–1.95 (1H, m), 2.44 (3H, s), 4.87–4.95 (1H, m), 6.32 (1H, d,
1.86 (2H, m), 4.84 (1H, t, J¼6.6 Hz), 6.29 (1H, s), 7.34–7.42 (3H, m),
J¼1.6 Hz), 7.14–7.37 (2H, m), 7.49–7.56 (2H, m); 13C NMR
d 22.3,
7.58–7.61 (2H, m); 13C NMR
d
ꢁ2.5, 13.7, 17.9, 35.2, 79.9, 127.9, 129.4,
22.7, 23.0, 25.2, 42.4, 78.9, 125.1, 129.9, 134.0, 136.1, 134.6, 136.1,
143.4, 152.8, 163.9; MS (EI) m/z (rel int.%): 288 (Mþ, 1), 273 (27), 231
(39), 197 (97), 159 (57), 149 (91), 121(76), 105 (36), 91 (85), 75 (100),
133.6, 141.1, 135.4, 152.7, 163.8; MS (EI) m/z (rel int.%): 260 (Mþ, 4);
245 (33); 217 (35); 149 (29); 145 (89); 135 (100); 105 (44); 75 (41);
IR
n
3055, 2955, 1805, 1461, 1422, 1244, 1105. Anal. Calcd for
53 (59); IR n 3044, 2944, 1811, 1461, 1283, 1255, 1111. Anal. Calcd for
C15H20O2Si: C, 69.19; H, 7.74; found: C, 69.25; H, 7.69.
C17H24O2Si: C, 70.78; H, 8.39; found: C, 70.61, H, 8.45.
4.3.2. (Z)-3-[(Dimethylphenylsilyl)-methylene]-4-ethyl-4-methyl-oxe
tan-2-one (Z)-4ea. The crude oil was purified by column chroma-
tography on silica gel using hexane/AcOEt¼90/10 as eluent (76%
4.3.8. (Z)-3-[(Biphenyl-4-yl-dimethyl-silyl)-methylene]-4-propyl-oxe-
tan-2-one (Z)-4be. The crude oil was purified by column chroma-
tography on silica gel using hexane/Et2O¼95/5 as eluent (12% yield);
yield); 1H NMR
d
0.54 (6H, s), 0.95 (3H, t, J¼7.3 Hz), 1.51 (3H, s),
1H NMR
d
0.61 (6H, s), 0.98 (3H, t, J¼7.2 Hz),1.41–1.56 (2H, m), 1.75–
1.75–1.90 (2H, m), 6.13 (1H, s), 7.23–7.52 (5H, m); 13C NMR
d
7.8,
1.86 (2H, m), 4.85 (1H, m), 6.29 (1H, s), 7.25–7.80 (9H, m); 13C NMR
22.8, 30.9, 87.4, 127.9, 129.4, 133.4, 133.6, 137.0, 156.0, 163.8; MS (EI)
d 2.4,13.8,18.0, 35.3, 80.0,126.7,127.3,127.1,127.4,135.3,135.5,137.3,
m/z (rel int.%): 260 (Mþ, 14), 245 (45), 231 (44), 183 (23), 169 (16),
141.0,141.2,141.9,142.3,152.9,165.6; MS (EI) m/z (rel int.%): 336 (Mþ,
145 (100), 135 (28),123 (20),105 (28), 75 (23); IR
n
3074, 2967, 1808,
26), 293 (52), 221 (90), 211 (100), 195 (70), 181 (74), 165 (82), 152

272
L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
(68), 105 (56), 75 (94); IR
Calcd for C21H24O2Si: C, 74.96; H, 7.19; found C, 75.91; H, 7.07.
n
3055, 2955, 1811, 1461, 1250, 1111. Anal.
temperature, 2 mL of TBAF (1 M in THF). The reaction mixture was
immediately hydrolysed with water, extracted with Et2O and the
organic layers were dried over Na2SO4. After concentration under
vacuum, the crude product was purified by column chromatogra-
phy on silica gel using CH2Cl2 as eluent, unless otherwise specified.
4.3.9. (Z)-3-[(tert-Butyldimethylsilyl)-methylene]-4-propyl-oxetan-
2-one (Z)-4bf. The crude oil waspurified bycolumn chromatography
on silica gel using hexane/Et2O¼95/5 as eluent (30%); 1H NMR
d 0.21
(3H, s), 0.22 (3H, s), 0.90 (9H, s), 0.96 (3H, t, J¼7.4 Hz), 1.36–1.55 (2H,
m), 1.70–1.82 (2H, m), 4.81 (1H, ddd, J¼6.9, 5.4, 1.5 Hz), 6.13 (1H, d,
4.4.1. (E)-2-Benzyl-hex-2-enal 822. The crude oil was purified by
column chromatography on silica gel using hexane/Et2O¼80/20 as
J¼1.5 Hz); 13C NMR
d
5.6,13.8,16.9,18.0, 26.2, 35.4, 79.9, 135.4,153.0,
eluent (35%); 1H NMR
d
1.04(3H, t J¼7.4 Hz); 1.52–1.70 (2H, m);
163.9; MS (EI) m/z (rel int.%): 225 (Mþ-15, 1), 197 (3), 184 (30), 139
2.44–2.55 (2H, m); 3.72 (2H, s); 6.70 (1H, t J¼7.3 Hz); 7.21–7.39 (5H,
(12), 109 (12), 85 (9), 75 (100), 59 (15); IR
n
2951, 1812, 1682, 1253,
m); 9.55 (1H, s); 13C NMR
d
13.77, 21.69, 29.64, 31.21, 125.98, 128.27,
1280, 1113. Anal. Calcd for C13H24O2Si: C, 64.95; H, 10.06; found: C,
65.25; H, 10.16.
128.33, 139.18, 142.49, 156.02, 194.56; MS (EI) m/z (rel int.%) 188
(Mþ, 37), 145 (100), 129 (33), 117 (45), 91 (94), 77 (20), 65 (20); IR
3022, 2955, 2333, 1938, 1883, 1805, 1693, 1638, 1455.
n
4.3.10. (Z)-4-Methyl-4-phenyl-3-[(dimethylphenyllsilyl)methylene]-
oxetan-2-one (Z)-4ha. The crude oil was purified by column chro-
matography on silica gel using hexane/Et2O¼70/30 as eluent (53%);
4.4.2. 3-Benzyl-4-ethyl-4-methyl-oxetan-2-one 9ea. Major isomer:
66%, 1H NMR
0.79 (3H, t, J¼7.4 Hz), 1.46 (3H, s), 1.68–1.95 (2H, m),
2.83–2.95 (1H, m), 3.51–3.64 (1H, m), 3.10–3.15 (1H, m), 7.20–7.40
(5H, m); 13C NMR
7.9, 19.1, 30.6, 33.4, 57.3, 82.9, 126.6, 128.2, 128.5,
137.5, 170.8; MS (EI) m/z (rel int.%): 203 (Mþ-1, 2), 160 (26), 131
(100),115(15),104 (14), 91 (60); IR 2966,1811,1450. Minor isomer:
1H NMR
1.0 (3H, t, J¼7.4 Hz), 1.51 (3H, s), 1.80–2.00 (2H, m), 2.95–
3.04 (2H, m), 3.55–3.68 (2H, m), 3.18–3.23 (1H, m), 7.20–7.40 (5H,
m); 13C NMR
7.6, 23.9, 29.8, 27.8, 59.1, 82.5, 126.5, 128.3, 128.5,
d
1H NMR
d 0.47 (3H, s), 0.51 (3H, s),1.83 (3H, s), 6.30 (1H, s), 7.27–7.36
(6H, m), 7.46–7.51 (4H, m); 13C NMR
d
ꢁ2.5, 25.7, 86.1, 124.6, 128.0,
d
128.2,128.6,129.5,133.6,136.7,140.2,134.8,156.6,163.8; MS (EI) m/z
(rel int.%): 264 (Mþ-44, 6), 205 (5),135 (100),128 (6),119 (3),105 (9),
n
51 (12); IR
n
3066, 2944, 1955, 1889, 1811, 1450, 1422, 1250, 1105.
d
Anal. Calcd for C19H20O2Si: C, 73.98; H, 6.54; found: C, 74.04; H, 6.61.
d
4.3.11. 1-(Dimethylphenylsilyl)-3-phenyl-1,2-butadiene 6. The crude
oil was purified by column chromatography on silica gel using
137.6, 170.8. Anal. Calcd for C13H16O2: C, 76.44; H, 7.90; found: C,
76.14; H, 7.98.
hexane/Et2O¼70/30 as eluent (41%); 1H NMR
d 0.33 (6H, s), 2.18
(3H, d, J¼3.6 Hz), 5.45 (1H, q, J¼3.6 Hz), 7.14–7.50 (10H, m); 13C
4.4.3. 3-Benzyl-1-oxa-spiro[3.5]nonan-2-one 9fa23. 68% Yield, 1H
NMR
d
1.02, 24.6, 84.2, 94.2, 125.1, 125.8, 126.9, 127.7, 127.8, 128.3,
NMR
d
1.36–2.11 (10H, m), 3.00–3.14 (2H, 2 dd, J¼9.2, 6.9, 15.0 Hz),
129.2, 133.0, 133.6, 133.6, 203.13; MS (EI) m/z (rel int.%): 264 (Mþ,
23), 249 (36), 145 (48), 135 (100), 129 (26), 121 (86), 105 (39). Anal.
Calcd for C18H20Si: C, 81.76; H, 7.62; found: C, 81.68; H, 7.67.
3.54–3.62 (1H, dd, J¼9.2, 6.9 Hz), 7.33–7.45 (5H, m); 13C NMR
d 21.9,
22.6, 24.8, 29.7, 31.3, 37.2, 58.6, 82.5, 126.7, 128.2, 128.7, 137.9, 171.3;
MS (EI) m/z (rel int.%) 186 (Mþ-44, 26), 129 (13), 115 (10), 104 (100),
95 (10), 91 (27); IR
n 2922, 1800, 1444.
4.3.12. 1-(Dimethylphenylsilyl)-3-phenyl-1-butyne 7. The crude oil
was purified by column chromatography on silica gel using hexane/
4.4.4. -3-Benzyl-4-tert-butyl -4-methyl-oxetan-2-one 9ga. 59% Yield,
Et2O¼70/30 as eluent (5%); 1H NMR
d
0.42 (6H, s), 1.64 (3H, d,
1H NMR
d
0.88 (9H, s), 1.57 (3H, s), 2.78–3.25 (2H, 2 dd, J¼8.6, 7.0,
J¼7 Hz), 3.86 (1H, q, J¼7 Hz), 7.12–7.60 (10H, m); MS (EI) m/z (rel
int.%): 264 (Mþ, 10), 249 (1), 204 (2), 135 (100), 128 (4), 105 (12).
Anal. Calcd for C18H20Si: C, 81.76; H, 7.62; found: C, 81.65; H, 7.55.
14.7 Hz), 3.78 (1H, dd, J¼8.6, 7.0 Hz), 7.26–7–38 (5H, m); 13C NMR
d
16.8, 24.3, 31.3, 36.2, 53.9, 86.8, 126.7, 128.6, 128.7, 137.8, 171.1; MS
(EI) m/z (rel int.%) 188 (Mþ-44, 2),132 (36),131 (100), 91 (36), 84 (21),
69 (15), 57 (13); IR 2955, 1811, 1450. Anal. Calcd for C15H20O2: C,
n
4.3.13. (Z)-3-[(Dimethylphenylsilyl)methylene]-5-ethyl-2(3H)-dihy-
77.55; H, 8.68; found: C, 77.36; H, 8.76.
drofuran (Z)-11a. The crude oil was purified by column chroma-
tography on silica gel using CH2Cl2 as eluent (64%); 1H NMR
d
0.51
4.4.5. 3-Benzyl-4-phenyl-4-methyl-oxetan-2-one 9ha. 30% Yield, 1H
(3H, s), 0.52 (3H, s), 0.98 (3H, t, J¼7.3 Hz), 1.57–1.84 (2H, m), 2.61
(1H, ddd, J¼17.3, 6.3, 2.7 Hz), 3.04 (1H, ddd, J¼17.3, 7.5, 2.7 Hz), 4.44
(1H, m), 6.50 (1H, m), 7.35–7.38 (3H, m), 7.58–7.61 (2H, m), 13C NMR
NMR
d
2.03 (3H, s), 2.48–2.89 (2H, 2 dd, J¼7.8, 8.8, 15.0 Hz), 4.00
(1H, dd, J¼7.8, 8.8 Hz), 7.29–7.47 (10H, m); 13C NMR
d 27.46, 32.0,
61.3, 82.5, 125.5, 126.6, 128.3, 128.4, 128.5, 128.6, 137.0, 137.5, 170.3;
d
ꢁ2.04, ꢁ2.07, 9.29, 29.42, 37.04, 78.81, 127.96, 129.13, 133.97,
139.51, 141.94, 142.53, 169.93; MS (EI) m/z (rel int.%): 245 (Mþ-15,
100),183 (87),169 (4),135 (4),105 (5), 77 (4), 75 (6); IR 3067, 2956,
IR n 2955, 1816, 1444. Anal. Calcd for C17H16O2: C, 80.93; H, 6.39;
found: C, 81.20; H, 6.48.
n
1956, 1889, 1828, 1465, 1426, 1245, 1111. Anal. Calcd for C15H20O2Si:
C, 69.19; H, 7.74; found: C, 69.33, H, 7.78.
4.4.6. 4-Isobutyl-3-(2-methylbenzyl)-oxetan-2-one 9cd. Major iso-
mer: 60%, 1H NMR
d
0.85 (6H, 2 d, J¼6.4, 7.0 Hz), 1.36–1.58 (2H, m),
1.64–1.75 (1H, m), 2.32 (3H, s), 2.93–3.24 (2H, 2 dd, J¼6.3, 9.5,
4.3.14. (Z)-3-[(Dimethylphenylsilyl)methylene]-5-phenyl-2(3H)-di-
14.7 Hz), 3.39–3.49 (1H, m), 4.31–4.39 (1H, m), 7.10–7.16 (4H, m);
hydrofuran (Z)-11b. The crude oil was purified by column chroma-
13C NMR
d
19.4, 22.5, 22.2, 25.1, 30.9, 43.4, 56.4, 76.6, 126.3, 127.1,
128.9, 130.6, 135.3, 135.8, 170.9; MS (EI) m/z (rel int.%) 188 (Mþ-44,
35), 131 (49), 117 (44), 105 (46), 41 (100), 39 (79); IR 2955, 1816,
1461. Minor isomer: 1H NMR
0.91–0.98 (6H, m),1.62–1.75 (2H, m),
tography on silica gel using CH2Cl2 as eluent (72%); 1H NMR
d 0.58
(3H, s), 0.59 (3H, s), 2.95 (1H, ddd, J¼17.1, 6.6, 2.4 Hz), 3.40 (1H, ddd,
n
J¼17.1, 7.8, 2.4 Hz), 5.52 (1H, dd, J¼7.8, 6.6 Hz), 6.60 (1H, t, J¼2.4 Hz),
d
7.30–7,79 (10H, m); 13C NMR
128.44, 128.76, 128.97, 133.74, 138.99, 139.98, 141.50, 142.61, 165.45.
Anal. Calcd for C19H20O2Si: C, 73.98; H, 6.54; found: C, 74.10; H, 6.57.
d
ꢁ2.33, 40.01, 77.96, 125.40, 127.75,
2.49 (3H, s), 2.93–3.24 (2H, m), 3.98–4.09 (1H, m), 4.71–4.81 (1H,
m), 7.10–7.16 (4H, m). Anal. Calcd for C15H20O2: C, 77.55; H, 8.68;
found: C, 77.75; H, 8.75.
4.4. General procedures for the TBAF promoted
rearrangements
4.4.7. 3-Benzyl-5-ethyl-dihydro-furan-2-one 12a24. 61% Yield of
a diastereoisomeric mixture; major isomer (Z): 1H NMR
d 0.94 (3H,
t, J¼7.5), 1.55 (1H, m), 1.46–1.78 (2H, m), 2.27 (1H, ddd, J¼12.6, 8.4,
To a solution of 2 mmol of
b-silylalkenal or (Z)-(dimethylary
5.4 Hz), 2.70 (1H, dd, J¼13.8, 9.6 Hz), 2.91 (1H, m), 3.28 (1H, dd,
lsilyl)methylene- -lactone in 10 mL of THF, were added, at room
b
J¼13.8, 4.2 Hz), 4.24 (1H, m), 7.24 (5H, m); 13C NMR
d 9.20, 28.18,

L.A. Aronica et al. / Tetrahedron 66 (2010) 265–273
273
223; (f) Church, T. L.; Getzler, Y. D. Y. L.; Byrne, C. M.; Coates, G. W. Chem.
Commun. 2007, 657; (g) Kramer, J. W.; Coates, G. W. Tetrahedron 2008, 64, 6973.
7. Matsuda, I.; Ogiso, A.; Sato, S. J. Am. Chem. Soc. 1990, 112, 6120.
8. Matsuda, I.; JP Patent 3148271, 1995; Chem. Abstr. 1991, 232059.
9. Aronica, L. A.; Caporusso, A. M.; Salvadori, P. Eur. J. Org. Chem. 2008, 3039 and
references therein.
34.09, 36.08, 42.73, 79.98, 126.76, 128.78, 128.91, 138.82, 178.21.
Minor isomer (E) 0.93 (3H, t, J¼7.5 Hz), 1.46–1.78 (2H, m), 1.92 (1H,
ddd, J¼13.2, 9.3, 5.1 Hz), 2.08 (1H, dt, J¼13.2, 7.5 Hz), 2.76 (1H, dd,
J¼13.5, 9.6 Hz), 2.91 (1H, m), 3.18 (1H, dd, J¼13.5, 4.2 Hz), 4.24 (1H,
m), 7.24 (5H, m); 13C NMR
d 9.36, 28.33, 31.97, 36.43, 40.96, 79.88,
10. Aronica, L. A.; Valentini, G.; Caporusso, A. M.; Salvadori, P. Tetrahedron 2007,
63, 6843.
126.86, 128.79, 129.02, 138.49, 178.77.
11. Aronica, L. A.; Morini, F.; Caporusso, A. M.; Salvadori, P. Tetrahedron Lett. 2002,
43, 5813.
12. Matsuda, I.; Niikawa, N.; Kuwabara, R.; Inoue, H.; Nagashima, H.; Itoh, K.
J. Organomet. Chem. 1999, 574, 133.
4.4.8. 3-Benzyl-5-phenyl-dihydro-furan-2-one 12b24c,25. 72% Yield
of a diastereoisomeric mixture; major isomer (Z): 1H NMR
d 1.84–
1.99 (1H, m), 2.56–2.65 (1H, m), 2.78 (1H, dd, J¼13.8, 9.6 Hz),
13. Aronica, L. A.; Raffa, P.; Caporusso, A. M.; Salvadori, P. J. Org. Chem. 2003, 68,
9292.
3.02–3.12 (1H, m), 3.35 (1H, dd, J¼13.8, 4.2 Hz), 5.33 (1H, dd,
14. (a) Adam, W.; Albert, R.; Hasemann, L.; Nava Salgado, V. O.; Nestker, B.; Peters,
E.-M.; Peters, K.; Prechtl, F.; Georg Von Shenering, H. J. Org. Chem. 1991, 56,
5782; (b) Danheiser, R. L.; Choi, Y. M.; Meninchincheri, M.; Stoner, E. J. J. Org.
Chem. 1993, 58, 322; (c) Morao, I.; Lecea, B.; Arrieta, A.; Cossio, F. P. J. Am. Chem.
Soc. 1997, 119, 816.
15. (a) Jones, E. R. H.; Mansfield, G. H.; Whiting, M. C. J. Chem. Soc. 1954, 3208; (b)
Pourcelot, G.; Cadiot, P. Tetrahedron 1982, 38, 2123; (c) Banert, K. Chem. Ber.
1989, 122, 1963; (d) Leise, M.; Lang, H.; Imohof, W.; Zsolnai, L. Chem. Ber. 1993,
126, 1077; (e) Banert, Klaus. Targets in Heterocyclic Systems; Societa` Chimica
Italiana: Roma, 1999; Vol. 3, 1; (f) Trofimov, B. A. Curr. Org. Chem. 2002, 6, 1121.
16. (a) Fleming, I.; Waterson, D. J. Chem. Soc., Perkin Trans. 11984, 1809; (b) Fleming,
I.; Terrett, N. K. J. Organomet. Chem. 1984, 264, 99; (c) Masse, C. E.; Panek, J. S.
Chem. Rev. 1995, 95, 1293; (d) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997,
97, 2063; (e) Marshall, J. A.; Adams, N. D. J. Org. Chem. 1997, 62, 8976; (f)
Marshall, J. A.; Maxson, K. J. Org. Chem. 2000, 65, 630; (g) Guitchin, B. K.; Bienz,
S. Organometallics 2004, 4944.
17. (a) Adam, W.; Hasemann, L.; Prechtl, F. Angew. Chem., Int. Ed. Engl. 1988, 27,
1536; (b) Cheikh, A. B.; Pommelet, J.-C.; Chuche, J. J. Chem. Soc., Chem. Commun.
1990, 615; (c) Campi, E. M.; Dyall, K.; Fallon, G.; Jackson, W. R.; Perlmutter, P.;
Smallridge, A. J. Synthesis 1990, 855; (d) Adam, W.; Rainer, A.; Dachs Grau, N.;
Hasemann, L.; Nestler, B.; Peters, E.-M.; Peters, K.; Prechtl, F.; Georg Von She-
nering, H. J. Org. Chem. 1991, 56, 5778; (e) Qing, F.-L.; Jiang, Z.-X. J. Fluorine Chem.
2002, 114, 177; (f) Martinez, I.; Andrews, A. E.; Emch, J. D.; Ndakala, A. J.; Wang,
J.; Howell, A. R. Org. Lett. 2003, 5, 399.
18. (a) Mulzer, J.; Kerkmann, T. J. Am. Chem. Soc. 1980, 102, 3620; (b) Carriere, F.;
Blottiau, R.; Sekiguchi, H. Eur. Polym. J. 1986, 22, 285; (c) Carriere, F.; Blottiau, R.
Bull. Soc. Chim. Fr. 1991, 717; (d) Scherowsky, G.; Sefkov, M. Chimia 1993, 47, 19.
19. (a) Kim, D. H.; Ryoo, J. J. Bioorg. Med. Chem. Lett. 1995, 5, 1287; (b) Kim, D. H.;
Park, J.; Chung, S. J.; Park, J. D.; Park, N.-K.; Han, J. H. Bioorg. Med. Chem. Lett.
2002, 10, 2553; (c) Purohit, V. C.; Richardson, R. D.; Smith, J. W.; Romo, D. J. Org.
Chem. 2006, 71, 4549.
J¼10.8, 5.8 Hz), 7.16–7.40 (10H, m); 13C NMR
d 36.07, 37.49, 43.30,
79.45, 124.85, 125.38, 126.68, 128.44, 128.67, 128.80, 138.41,
138.96, 177.65. Minor isomer (E): 1H NMR
d 2.22–2.26 (1H, m),
2.41–2.51 (1H, m), 2.86 (1H, dd, J¼13.2, 9.6 Hz), 2.93–3.20 (1H, m),
3.23 (1H, dd, J¼13.2, 4.2 Hz), 5.33 (1H, dd, J¼10.8, 5.8 Hz), 7.16–
7.40 (10H, m).
References and notes
1. (a) Pommier, A.; Pons, J. M. Synthesis 1995, 729; (b) Lower, C.; Vederas, J. C. Org.
Prep. Proced. Int. 1995, 27, 305 and references therein.
2. (a) Borgstrom, B. Biochim. Biophys. Acta 1988, 962, 308; (b) Stalder, H.;
Schneider, P. R.; Oesterhelt, G. Helv. Chim. Acta 1990, 73, 1022; (c) Zhi, J.; Melia,
A. T.; Guerciolini, R.; Chung, J.; Kinberg, J.; Hauptman, J. B.; Patel, I. H. Clin.
Pharmacol. Ther. 1994, 56, 82; (d) Majama, M.; Kuribayashi, Y.; Ikeda, Y.; Adachi,
K.; Kato, H.; Katori, M.; Aoyagi, T. Jpn. J. Pharmacol. 1994, 65, 79; (e) Scaloni, A.;
Jones, W. M.; Barra, D.; Pospischil, M.; Sassa, S.; Popowicz, A.; Manning, L. R.;
Schneewind, O.; Manning, J. M. J. Biol. Chem. 1992, 267, 3811; (f) Koller, W.; Trail,
F.; Parker, D. M. J. Antibiot. 1990, 43, 734; (g) Kondo, S.; Uotani, K.; M; Miyamoto,
M.; Hazato, T.; Naganawa, H.; Aoyagi, T. J. Antibiot. 1978, 31, 797; (h) Umezawa,
H.; Aoyagi, T.; Hazato, T.; Uotani, K.; Kojima, F.; Hamada, M.; Takeuchi, T.
J. Antibiot. 1978, 31, 639; (i) Imanaka, T.; Moriyama, Y.; Ecsedi, G. G.; Aoyagi, T.;
Amanuma-Muto, K.; Ohkuma, S.; Takano, T. J. Biochem. 1983, 94, 1017; (j) Kudo,
Y.; Oka, J.-I.; Yamada, K. Neurosci. Lett. 1981, 25, 83.
3. Wang, Y.; Tennyson, R. L.; Romo, D. Heterocycles 2004, 64, 605 and references
therein.
4. (a) Jedlinski, Z.; Kurcok, P. Kowalcuzuk, M.; Matuszowicz, A.; Dubois, P.; Jerome,
R.; Kricheldorf, A.R. Macromolecules 28, 7276 (b) Jedlinski, Z. J. Heterocycl.
Chem. 2001, 38, 1249; (c) Jaipuri, F. A.; Bower, B. D.; Pohl, N. L. Tetrahedron:
Asymmetry 2003, 14, 3249.
5. (a) Pommier, A.; Pons, J. M. Synthesis 1993, 441; (b) Yang, H. W.; Romo, D.
Tetrahedron 1999, 55, 6403; (c) Collins, I. J. Chem. Soc., Perkin Trans. 11999, 1377;
Tidwell, T. T. Eur. J. Org. Chem. 2006, 563; Purohit, V. C.; Matla, A. S.; Romo, D.
Heterocycles 2008, 76, 949 and references therein.
6. (a) Lee, J. T.; Thomas, P. J.; Alper, H. J. Org. Chem. 2001, 66, 5424; (b) Getzler, Y. D.
Y. L.; Mahedevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124,
1174; (c) Molnar, F.; Luinstra, G. A.; Allmendinger, M.; Rieger, B. Chem.d Eur. J.
2003, 9, 1273; (d) Schimdt, J. A. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem.
Soc. 2005, 127, 11426; (e) Nakano, K.; Nozaki, K. Top. Organomet. Chem. 2006, 12,
20. Fujita, M.; Hiyama, T. J. Org. Chem. 1988, 53, 5405.
21. Martinengo, S.; Giordano, G.; Chini, P. Inorg. Synth. 1990, 28, 242.
22. Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96, 7503.
23. Wedler, C.; Kleiner, K.; Kunath, A.; Schick, H. Lieb. Ann. 1996, 6, 881.
24. (a) Li, B.; Buzon, R. A.; Castaldi, M. J. Org. Process Res. Dev. 2001, 5, 609; (b)
Oswald, M. F.; Parsons, A. F.; Yang, W.; Bowden, M. Tetrahedron Lett. 2005,
46, 8087; (c) Domingo, L. R.; Gil, S.; Parra, M.; Segura, J. Molecules 2008, 13,
1303.
25. (a) McWilliams, J. C.; Armstrong, J. D.; Zheng, N.; bhupathy, M.; Volante, R. P.;
Reider, P. J. J. Am. Chem. Soc. 1996, 118, 11970; (b) Ghosh, A. K.; Shurrush, K.;
Kulkarni, S. J. Org. Chem. 2009, 74, 4508.