Reaction of silyl ketene acetals with epoxides: A new method for the synthesis of γ-butanolides

Article abstract of DOI:10.1016/j.tet.2004.07.007

Titanium tetrachloride promoted reaction of silyl ketene acetals with epoxides, followed by acidic work-up, affords butanolides in moderate/good yields. With epihalohydrins the reaction is regioselective and occurs at the less substituted end of the epoxide; the γ-haloalkyl-γ-butanolides thus obtained can be further transformed into various products. Graphical Abstract

Full text of DOI:10.1016/j.tet.2004.07.007

Tetrahedron 60 (2004) 8957–8966
Reaction of silyl ketene acetals with epoxides: a new method for
the synthesis of g-butanolides
b
Veselin Maslak,a,b Radomir Matovic and Radomir N. Saicic
ˇ ´a,b,
*
´
aFaculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 158, 11000 Belgrade, Serbia and Montenegro
b
ˇ
I. C. T. M. Center for Chemistry, Njegoseva 12, 11000 Belgrade, Serbia and Montenegro
Received 10 March 2004; revised 9 June 2004; accepted 1 July 2004
Available online 23 August 2004
Abstract—Titanium tetrachloride promoted reaction of silyl ketene acetals with epoxides, followed by acidic work-up, affords butanolides
in moderate/good yields. With epihalohydrins the reaction is regioselective and occurs at the less substituted end of the epoxide; the
g-haloalkyl-g-butanolides thus obtained can be further transformed into various products.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Epoxide ring opening with carbon nucleophiles is one of the
most useful reactions in organic synthesis.1 However, the
role of nucleophile is usually conferred to organometallics,
while the analogous reactions of ketone and ester enolates
are generally less efficient. While the group I and II ketone
enolates do not react with epoxides at all, g-hydroxyketones
can be obtained when the reaction is performed in the
presence of boron trifluoride etherate,2 scandium triflate,3 in
5 M etheral solution of lithium perchlorate4 or, indirectly,
with the enolate of the corresponding imine5 or N,N-
dimethylhydrazone.6 Similarly, although sporadic examples
of epoxide ring opening with lithium mono- and dianions of
carboxylic acids and derivatives have been reported,7 these
species are essentially unreactive towards epoxides and
their reactions have not found broad synthetic application.
Aluminum ester enolates, which can be obtained by
transmetallation of their lithium counterperts with chloro-
alanes are much more reactive and their reactions with
epoxides offer an efficient approach to g-hydroxy car-
boxylic acid derivatives and butanolides.8 Reactions of
epoxides with enolates have been recently reviewed.9
Indirect methods for butanolide synthesis have also been
devised, relying on reactions of alkoxyalkynilalanes8a or,
more recently, silylynamines as the reactive
intermediates.10
Some time ago, we found that silyl enol ethers react with
epoxides under the conditions of the Mukaiyama reaction,
to give the homoaldol type products.11 The reaction,
initially suspected to proceed via the titanium enolate, was
subsequently shown to involve the catalysis by TiCl4 as a
Lewis acid.12 In this way, the scope of the homoaldol
transform, represented by the Eq. (1) in Scheme 1, was
enlarged by a new synthetic transformation, complementary
to the existing ones. We now wish to report the extension of
this method to silyl ketene acetals, which offers an
alternative synthetic approach to g-butanolides (Eq. (2)).
Scheme 1. Homoaldol transforms for g-hydroxyketones and butanolides.
When a dichloromethane solution of silyl ketene acetal
(SKA) 1, prepared from isopropyl phenylbutanoate,14 and
ethylene oxide was submitted to the action of TiCl4 at
K60 8C, the TLC of the reaction mixture indicated the
formation of two products which, upon acidic work-up,
converged to a single compound—a-(2-phenylethyl)-g-
butanolide 2—which was isolated in 19% yield (Scheme 2).
Other Lewis acids (BF3$Et2O, ZnCl2, Ti(OiPr)4, SnCl4,
Keywords: Epoxides; Ketene acetals; Lactones; Titanium and compounds;
Alkylation.
* Corresponding author. Address: Faculty of Chemistry, University of
Belgrade, Studentski trg 16, PO Box 158, 11000 Belgrade, Serbia and
Montenegro. Tel.: C381 113282537; fax: C381 11636061;
e-mail: rsaicic@chem.bg.ac.yu
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.007

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V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
Table 2. Reactions with epichloro- and epibromohydrin
Entry
Reactant
Product
Yield
(%)a
1
13 XZCl
14 XZBr
1.
2.
49
50
3
15 XZCl
16 XZBr
3.
4.
64
64
5.
83
4
Scheme 2. The first experiments with ethylene oxide.
17
TMSOTf) were ineffective catalysts for this transformation.
Reducing the size of the ester alkyl group proved beneficial,
as substituting the smaller methyl group for isopropyl in 1
increased the yield to 38%. Further improvements were
achieved by performing the reaction in the mixed solvent: n-
hexane/dichloromethaneZ2/1, which resulted in the yield
enhancement to 62% (97%, based on the recovered methyl
4-phenylbutanoate). The best results were obtained when
the reagents were used in the molar ratio: SKA/ethylene
oxide/TiCl4Z1/2/3; change in the molar ratio, or the
alternative order of addition, decreased the yield.
18
6.
7.
8.
44
69
59
5
19
20
6
11
Several other SKA were submitted to these reaction
conditions. In all cases the desired g-butyrolactones were
obtained in 53–69% yields, as shown in Table 1. The
reaction proved suitable for the preparation of lactones
possessing a saturated (entry 2), unsaturated (entry 3) or a
side chain with an aromatic unit (entry 1), as well as those
9.
54
12
21
a
Isolated yields of pure products.
Table 1. Reactions of SKA with ethylene oxide
possessing a quaternary center in the a-position (entry 4),
including spirolactones (entry 5).
Entry
Reactant
Product
Yield (%)a
62 (97)b
1
A higher level of product functionalization was obtained
when performing the reaction with epihalohydrins. Thus,
both epichloro- and epibromohydrin reacted with a range of
SKA to afford the corresponding g-halomethylbutanolides
in 44–83% yield (Table 2). Owing to a negative inductive
effect of the halide substituent, the epoxide ring opening is
regioselective, with the nucleophilic attack occurring
exclusively at the less substituted epoxide end. The reaction
is not stereoselective, however, as the products were
obtained as equimolar mixtures of cis and trans isomers.
2
1.
3
7
2.
69
64
4
8
3.
4.
5
Bis-trimethylsilyl ketene acetals, which can be obtained
from carboxylic acids, are also efficient reaction partners.
As can be seen from Table 3, the yields in their reactions
with ethylene oxide and epihalohydrins compare favourably
with those of SKA.
9
53
66
6
10
5.
We also examined the reaction of SKA with substituted
epibromohydrins of type 24. These compounds can be
a
Isolated yields of pure products.
Yield calculated on the basis of recovered methyl 4-phenylbutanoate.
b

V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
8959
Table 3. Reactions of bis-SKA
Entry
Reactants
Product
Yield (%)a
22
22C
22C
1.
2.
2
66
59
13
Scheme 3. Synthesis of substituted epibromohydrins.
53 (73%b)
of configuration of the stereocenters originating from the
bromohydrin.
22C
3.
14
23
Reactions with epoxides that do not possess a halide
substituent in the vicinal position were less successful
(Table 5). Alkylation of 3 with cyclohexene oxide furnished
the condensed bicyclic lactone 33 in an acceptable 48%
yield (entry 1), but with the structurally similar SKA 1 and
23 lower yields were obtained. The reactions with propene
oxide gave rise to mixtures of regioisomers which were
isolated in modest yields (entries 2–4). In the case of styrene
oxide, the reaction could be performed in the presence of
BF3$Et2O, and gave the 3-phenylbutanolide derivative 40
regioselectively (entry 5; this is the only case where the
23C
23C
4.
5.
7
80
67
15
a
Isolated yields of pure products.
Yield determined.
b
stereoselectively obtained by a four-step sequence displayed
in Scheme 3.
Table 5. Reactions of SKA with epoxides other than epihalohydrins
The results of SKA alkylation with substituted epibromo-
hydrins of type 24 are displayed in Table 4. No isomeriza-
tion occurs under the reaction conditions and all the
products were obtained as syn-isomers, with the retention
Entry
Reactants
Product
Yield
(%)a
1.
33
48
3C
Table 4. Alkylations of SKA with substituted epibromohydrins
Entry
Reactants
Product
Yield
(%)a
34
35
1C
1.
28
73
66
54
21
69
3C
25
C
2.
29
}
2.
3.
4.
29
3C
26
(1:1 mixture of regioisomers)
3.
4.
36C37
35
38
6C
5C
30
31
32
3C
27
26
(1:1 mixture of regioisomers)
38C39
12C
(1:1 mixture of regioisomers)
15,
32b
5.
40
5.
5C
11C
27
a
Isolated yields of pure products.
BF3Et2O was used instead of TiCl4.
a
b
Isolated yields of pure products.

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V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
halogen-containing epoxides, does not necessarily restrict
the scope of the reaction to the synthesis of quite simple
derivatives, as the products of the coupling with epihalohy-
drins are amenable to further synthetic transformations
(Scheme 4). Thus, the combination of the alkylation with
epihalohydrin and the reduction with tributyltinhydride
affords regioselectively g-alkyl substituted butanolides,
which are not directly obtainable by the reaction with the
corresponding unsymmetrical epoxides (Table 6, entries 1,
3–6). This transformation can also be carried out with
hypophosphorous acid as a non-toxic and environmentally-
friendly reagent (entry 2).15 Carbon–carbon bond forming
reactions are also possible, and the examples of allylation
and of the Giese addition are given in entries 7 and 8,
respectively. Radical reactions are particularly well suited
for these type of transformations as, in contrast to b-alkoxy
organometallics, b-alkoxy radical intermediates are not
susceptible to b-elimination. These combinations of reac-
tions are the synthetic equivalents of the alkylation with
structurally more complex epoxides.
Scheme 4. Transformations of products.
coupling could be achieved with a Lewis acid other than
TiCl4).
In conclusion, a new reaction of silyl ketene acetals with
epoxides is described, which complements the existing
methods for the synthesis of g-butanolides.
However, the poor performance of unsymmetrical, non-
Table 6. Transformations of 4-haloalkylbutanolides
Entry
Reactants
Products
Yield (%)a
14
34
1.
2.
Bu3SnH
H3PO2
73
76
15
19
41
36
42
3.
4.
5.
Bu3SnH
Bu3SnH
Bu3SnH
74
78
80
21
43
28
6.
7.
Bu3SnH
82
83
76
16
44
45
28
8.
a
Yield of the isolated pure compound.

V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
8961
3. Experimental
silane (6). 74%. Colorless oil, bp 80 8C/25 mmHg; spectro-
scopic data identical to that reported in the literature.14
3.1. General
3.2.6. 3-Methyl-1-methoxy-1-trimethylsilyloxy-1-butene
(11). 40%. Colorless oil, bp 45 8C/1 mmHg. Spectroscopic
data for this compound have not been reported in the
literature.13b 1H NMR d: 3.66–3.45 (m, 4H); 2.56–2.45 (m,
1H); 0.93 (d, JZ6.8 Hz, 6H); 0.22 (s, 9H).
All chromatographic separations were performed on Silica,
10–18, 60A, ICN Biomedicals. Standard techniques were
used for the purification of reagents and solvents. NMR
spectra were recorded on a Varian Genmini 200, 1H NMR at
200 MHz, 13C NMR at 50 MHz, for samples in deuterated
chloroform. Chemical shifts are expressed in ppm using
tetramethylsilane as internal standard, coupling constants
(J) are in Hz. IR spectra were recorded on a Perkin–Elmer
3.2.7. 3-Phenyl-1-methoxy-1-trimethylsilyloxy-1-pro-
pene (12). 53%. Colorless oil, bp 85 8C/1 mmHg; spectro-
scopic data identical to that reported in the literature.19
457 grating FT instrument, and are expressed in cmK1
.
Mass spectra were obtained on a Finnigan ITDS 700
instrument. Microanalyses were performed at the Vario EL
III instrument CHNOS Elementar Analyzer, Elemantar
Analysensysteme GmbH, Hanau-Germany. Melting points
were determined on a Kofler hot-stage apparatus and are
uncorrected. GC analyses were performed on a Varian 3400
instrument, equipped with Varian 4270 integrator,
VOCOLe column (105 m, ID: 0.53 mm, film thickness
3.0 mm, carrier gas H2, 10 mL/min), FI detector. Preparative
gas chromatography was performed on a Varian P-90
instrument, using 2 m long stainless steel column packed
with 10% OV-101 on Chromosorb 80, (carrier gas H2,
10 mL/min).
3.2.8. 4-Phenyl-1,1-bis(trimethylsilyloxy)-1-butene (22).
72%. Colorless oil, bp 130 8C/0.2 mmHg. Due to its lability,
compound 22 has not been fully characterized, but was
identified only by 1H NMR spectrum. 1H NMR d: 7.30–7.11
(m, 5H); 3.55 (t, JZ7.2 Hz, 1H); 2.64–2.51 (m, 2H); 2.28–
2.11 (m, 2H); 0.19 (s, 9H); 0.17 (s, 9H).
3.2.9. 1,1-Bis(trimethylsilyloxy)-1-hexene (23). 95%. Col-
orless oil, bp 80 8C/1 mmHg. Due to its lability, compound
23 has not been fully characterized, but was identified only
by 1H NMR spectrum. 1H NMR d: 3.55 (t, JZ7.2 Hz, 1H);
1.96–1.86 (m, 2H); 1.33–1.22 (m, 4H); 0.92–0.85 (m, 3H);
0.21 (s, 9H); 0.17 (s, 9H).
3.2. General procedure for the synthesis of silyl ketene
acetals.14
3.3. Synthesis of g-butanolides. General procedure for
the alkylation of silyl ketene acetals with epoxydes
To a cold (K78 8C) solution of LDA (13 mmol) in THF
(13 mL) was added a solution of the corresponding ester
(10 mmol) in THF (10 mL), dropwise, with stirring. After
30 min, TMSCl (2.16 g; 20 mmol) was added, the mixture
was stirred for additional 30 min at K78 8C, then allowed to
reach rt. The solvent was removed at the rotary evaporator,
the product was extracted from the residue with n-hexane,
the organic extract was concentrated at the rotavapor and the
residue was distilled under reduced pressure.
To a cold (K60 8C) solution of silyl ketene acetal (1 mmol)
and epoxide (2 mmol) in a solvent mixture dichloro-
methane–n-hexaneZ1:2 (3 mL) was added dropwise a
solution of TiCl4 in dichloromethane (0.82 mL of the
3.65 M solution; 3 mmol), with stirring under an argon
atmosphere. The reaction mixture was allowed to reach K
20 8C, then cooled to K30 8C and quenched by the addition
of conc. aq NH4Cl (5 mL). The organic phase was
separated, and the aqueous layer was extracted with
dichloromethane (3!10 mL). To a combined extract was
added p-TsOH (20 mg; 0.1 mmol) and the reaction mixture
was stirred 3 h at rt. The solution was washed with water,
dried over anh. Na2SO4 and concentrated under reduced
pressure. Purification by dry-flash chromatography afforded
the corresponding g-butanolides.
3.2.1. 4-Phenyl-1-methoxy-1-trimethylsilyloxy-1-butene
(1). 82%. Colorless oil, bp 95 8C/0.4 mmHg. Spectroscopic
data for this compound have not been reported in the
literature.16 1H NMR d: 7.82–7.60 (m, 5H); 4.20–3.90 (m,
4H); 3.20–3.05 (m, 2H); 2.85–2.75 (m, 2H); 0.18 (s, 9H).
3.2.2. 1-Methoxy-1-trimethylsilyloxy-1-hexene (3). 60%.
Colorless oil, bp 55–8 8C/2 mmHg; spectroscopic data
identical to that reported in the literature.17
3.3.1. 2-(2-Phenylethyl)-4-butanolide (2). Purification by
dry-flash chromatography was performed using 20%
acetone in petroleum–ether as an eluent, to give the title
compound in 66% yield when the reaction is performed with
4-phenyl-1,1-bis(trimethylsilyloxy)-1-butene 22, (when 4-
phenyl-1-methoxy-1-trimethylsilyloxy-1-butene 1 was used
as the starting compound the yield was 62%). Colorless oil,
bp 135–145 8C/0.3 mmHg (Kugelrohr). IRfilm: 3063, 3029,
3.2.3. 1-Methoxy-1-trimethylsilyloxy-1,5-hexadiene (4).
79%. Colorless oil, bp 40 8C/1 mmHg. Spectroscopic data
for this compound have not been reported in the literature.18
1H NMR d: 5.90–5.70 (m, 1H); 5.05–4.90 (m, 2H). 3.90–
3.80 (m, 1H); 3.50 (s, 3H, major isomer); 3.45 (s, 3H, minor
isomer); 2.07–2.04 (m, 4H); 0.22 (s, 9H).
1
2922, 2861, 1769, 1495, 1454, 1376, 1184, 1150, 1026, H
NMR d: 7.40–7.10 (m, 5H); 4.34 (ddd, J1ZJ2Z9.0 Hz,
J3Z2.7 Hz, 1H); 4.16 (ddd, J1ZJ2Z9.0 Hz, J3Z6.6 Hz,
1H); 2.85–2.60 (m, 2H); 2.60–2.10 (m, 3H); 2.10–1.60 (m,
2H); 13C NMR d: 179.3; 140.7; 128.4; 128.3; 126.1; 66.3;
38.2; 33.1; 31.8; 28.6; HRMS (EI): MC, found 190.0997;
C12H14O2 requires 190.0994. MS (EI) m/z: 190 (MC, 17%);
105 (15%); 91 (25%); 85 (100%).
3.2.4. 2-Methyl-1-methoxy-1-trimethylsilyloxy-1-pro-
pene (5). 52%. Colorless oil, bp 63 8C/25 mmHg; spectro-
scopic data identical to that reported in the literature.14
3.2.5. (Cyclohexylidene(methoxy)methoxy)trimethyl-

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V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
3.3.2. 2-Butyl-4-butanolide (7). Colorless oil, 80% from
1,1-bis(trimetilsilyloxy)-1-hexene, (69% from 1-methoxy-
1-trimethylsilyloxy-1-hexene). Spectroscopic data for this
140.5; 128.5; 128.4; 126.3; 76.0; 75.9; 39.7; 38.2; 34.0;
33.6; 33.4; 33.2; 33.1; 32.8; 32.0; 31.8.
compound have not been reported in the literature.20 IRfilm
:
3.3.8. 2-Butyl-4-chloromethyl-4-butanolide (15). Color-
less oil, 67% from 1,1-bis(trimetilsilyloxy)-1-hexene, (64%
from 1-methoxy-1-trimethylsilyloxy-1-hexene), obtained as
a 1:1 mixture of stereoisomers. Anal. Calcd for C9H15ClO2:
C 56.69, H 7.93; found: C 56.84, H 7.78; HRMS (EI): MC,
3053, 2959, 2931, 1773, 1462, 1376, 1168, 1026; 1H NMR
d: 4.35 (ddd, J1ZJ2Z9.0 Hz, J3Z3.0 Hz, 1H); 4.20 (ddd
J1ZJ2Z9.0 Hz, J3Z6.4 Hz, 1H); 2.60–2.30 (m, 2H); 2.10–
1.80 (m, 2H); 1.60–1.25 (m, 5H); 1.00–0.80 (m, 3H); 13C
NMR d: 179.6; 66.4; 39.0; 29.8; 29.3; 28.4; 22.2; 13.7.
found 190.07821; C12H14O2 requires 190.07606; IRfilm
:
3055, 2959, 2934, 1775, 1461, 1345, 1175; 1H NMR d: 4.76
(ddt, J1Z8.6 Hz, J2ZJ3Z4.4 Hz, 1H, diastereoisomer A);
4.64 (ddt, J1Z10.0 Hz, J2Z5.6 Hz, J3Z5.1 Hz, 1H,
diastereoisomer B); 3.80–3.65 (m, 2H); 2.80–2.40 (m,
2H); 2.40–2.00 (m, 1H); 2.00–1.30 (m, 6H); 1.00–0.80 (m,
3H); 13C NMR d: 178.5; 177.8; 76.3; 76.1; 48.5; 46.1; 45.3;
40.3; 38.8; 31.9; 30.7; 29.8; 29.2; 29.1; 22.2; 13.7.
3.3.3. 2-(3-Butenyl)-4-butanolide (8). Colorless oil, 64%,
spectroscopic data identical to that reported in the
literature.21 13C NMR spectra for this compound have not
been reported; 13C NMR d: 179.2 (C); 136.9 (CH); 115.2
(CH2); 66.1 (CH2); 38.1 (CH); 30.9 (CH2); 29.0 (CH2); 28.2
(CH2).
3.3.4. 2,2-Dimethyl-4-butanolide (9). Colorless oil, 53%,
spectroscopic data identical to that reported in the
literature.21 13C NMR spectra for this compound have not
been reported; 13C NMR d: 182.0; 64.4; 38.1; 36.4; 23.6.
3.3.9. 2-Butyl-4-bromomethyl-4-butanolide (16). Color-
less oil, 64%, obtained as a 1:1 mixture of stereoisomers.
Anal. Calcd for C9H15BrO2: C 45.98, H 6.43; found: C
45.74, H 6.55; IRfilm: 2958, 2933, 2864, 1777, 1461, 1343,
1174. Isomer A: 1H NMR d: 4.75 (ddt, J1Z8.2 Hz, J2ZJ3Z
5.0 Hz, 1H); 3.55 (d, JZ5.0 Hz, 2H); 2.82–2.66 (m, 1H);
2.39 (ddd, J1Z13.4 Hz, J2Z9.6 Hz, J3Z4.6 Hz, 1H); 2.17
(ddd, J1Z13.4 Hz, J2ZJ3Z7.9 Hz, 1H); 1.92–1.79 (m,
1H); 1.58–1.27 (m, 5H); 0.95–0.88 (m, 3H); 13C NMR d:
178.4 (C); 75.9 (CH); 38.8 (CH); 34.3 (CH2); 31.6 (CH2);
30.5 (CH2); 29.0 (CH2); 22.1 (CH2); 13.6 (CH3). Isomer B:
1H NMR d: 4.60 (ddt, J1Z10.4 Hz, J2ZJ3Z5.6 Hz, 1H);
3.57 (d, JZ5.6 Hz, 2H); 2.75–2.51 (m, 2H); 1.95–1.65 (m,
2H); 1.52–1.27 (m, 5H); 0.95–0.88 (m, 3H); 13C NMR d:
177.7 (C); 75.9 (CH); 40.4 (CH); 33.5 (CH2); 33.1 (CH2);
29.6 (CH2); 29.0 (CH2); 22.1 (CH2); 13.5 (CH3).
3.3.5. 2-Oxa-spiro[4.5]decan-1-one (10). Colorless oil,
1
66%. H NMR d: 4.26 (t, JZ7.1 Hz, 2H); 2.16 (t, JZ
7.1 Hz, 2H); 1.80–1.20 (m, 10H); 13C NMR d: 181.9; 65.1;
43.0; 32.9; 32.2; 25.2; 22.0; HRMS (EI): MC, found
154.0976; C12H20O2 requires 154.0994; MS (EI) m/z: 154
(MC, 32%); 99 (100%); 86 (82%); 81 (56%); 67 (32%).
3.3.6. 2-(2-Phenylethyl)-4-chloromethyl-4-butanolide
(13). Colorless oil, 60% from 4-phenyl-1,1-bis(trimethylsi-
lyloxy)-1-butene 22 (49% from 4-phenyl-1-methoxy-1-
trimethylsilyloxy-1-butene 1), obtained as a 1:1 mixture of
stereoisomers. The isomers were preparatively separated by
a second dry-flash chromatography, using 5% acetone in
petroleum–ether as an eluent. Anal. Calcd for C13H15ClO2:
3.3.10. 2-(3-Butenyl)-4-chloromethyl-4-butanolide (17).
Colorless oil, 83%, obtained as a 1:1 mixture of diastereoi-
somers, which could not be separated by column chroma-
tography, but were separated by preparative gas
chromatography. Bp 100–105 8C/0.3 mmHg (Kugelrohr,
for the mixture of isomers). Anal. Calcd for C9H13O2: C
C 65.41, H 6.33; Found: C 65.88, H 6.34. Isomer A: IRfilm
:
3028, 2950, 1773, 1603, 1496, 1453, 1167, 1033; 1H NMR
d: 7.40–7.10 (m, 5H); 4.74 (ddt, J1ZJ2Z8.6 Hz, J3Z
4.7 Hz, 1H); 3.65 (d, JZ4.7 Hz, 2H); 2.90–2.60 (m, 3H);
2.45–2.25 (m, 1H); 2.25–2.00 (m, 2H); 1.90–1.70 (m, 1H);
13C NMR d: 178.3 (C); 140.5 (C); 128.5 (CH); 128.3 (CH);
126.2 (CH); 76.1 (CH); 45.9 (CH2); 38.1 (CH); 33.1 (CH2);
32.8 (CH2); 30.9 (CH2). Isomer B: IRfilm: 3027, 2925, 1775,
57.30; H 6.95; Found: C 56.98; H 6.98. Isomer A: IRfilm
:
3074, 2919, 2862, 1774, 1641, 1347, 1170, 1038; 1H NMR
d: 5.90–5.70 (m, 1H); 5.15–4.95 (m, 2H); 4.76 (app. hex.,
JZ4.6 Hz, 1H); 3.71 (dd, J1ZJ2Z5.4 Hz, 2H); 2.85–2.65
(m, 1H); 2.60–2.30 (m, 2H); 2.30–1.90 (m, 2H); 1.70–1.50
(m, 2H); 13C NMR d: 178.6; 136.9; 115.9; 76.2; 46.0; 38.2;
31.2; 30.8; 30.3. Isomer B: 3074, 2939, 2864, 1775, 1641,
1345, 1172, 1037; 1H NMR d: 5.89–5.69 (m, 1H); 5.15–4.95
(m, 2H); 4.60 (m, 1H); 3.71 (dd, J1Z5.2 Hz, J2Z1.1 Hz,
2H); 2.80–2.40 (m, 2H); 2.30–2.00 (m, 3H); 1.95–1.50 (m,
2H); 13C NMR d: 177.8; 137.0; 115.9; 76.3; 45.3; 39.6;
32.2; 31.2; 29.4.
1
1603, 1496, 1453, 1165, 1035; H NMR d: 7.40–7.20 (m,
5H); 4.57 (ddt, J1ZJ2Z10.2 Hz, J3Z5.0 Hz, 1H); 3.69 (d,
JZ5.0 Hz, 2H); 2.90–2.40 (m, 4H); 2.40–2.20 (m, 1H);
1.90–1.70 (m, 2H); 13C NMR d: 177.7 (C); 140.5 (C); 128.5
(CH); 128.4 (CH); 126.3 (CH); 76.3 (CH); 45.3 (CH2); 39.5
(CH); 33.1 (CH2); 32.2 (CH2); 31.9 (CH2).
3.3.7. 2-(2-Phenylethyl)-4-bromomethyl-4-butanolide
(14). Colorless oil, 53% from 4-phenyl-1,1-bis(trimethylsi-
lyloxy)-1-butene 22, (50% from 4-phenyl-1-methoxy-1-
trimethylsilyloxy-1-butene 1), obtained as a 1:1 mixture of
stereoisomers. Anal. Calcd for C13H15BrO2: C 55.14, H
5.34; found: C 55.16, H 5.58; IRfilm: 3020, 2949, 2861,
3.3.11. 2,2-Dimethyl-4-chloromethyl-4-butanolide (18).
Colorless oil, 44%. Spectroscopic data for this com-
pound have not been reported in the literature.8c IRfilm
:
1
2968, 2933, 1775, 1461, 1385, 1207, 1117; H NMR d:
4.69 (ddt, J1Z9.4 Hz, J2Z6.5 Hz, J3Z5.2 Hz, 1H); 3.70
(d, JZ5.2 Hz, 2H); 2.24 (dd, J1Z12.9 Hz, J2Z6.5 Hz,
1H); 2.00 (dd, J1Z12.9 Hz, J2Z9.4 Hz, 1H); 1.32 (s.
3H); 1.30 (s. 3H); 13C NMR d: 180.9; 74.9; 45.5; 40.5;
40.2; 24.9; 24.8.
1
1768, 1602, 1494, 1454, 1160; H NMR d: 7.35–7.18 (m,
5H); 4.74 (ddt, J1Z8.1 Hz, J2Z5.7 Hz, J3Z4.4 Hz, 1H,
isomer A); 4.54 (ddt, J1Z10.3 Hz, J2ZJ3Z4.0 Hz, 1H,
isomer B); 3.62–3.42 (m, 2H); 2.89–2.48 (m, 3H); 2.41–
2.06 (m, 2H); 1.88–1.66 (m, 2H); 13C NMR d: 178.3; 177.6;

V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
8963
3.3.12. 3-Chloromethyl-2-oxa-spiro[4.5]decan-1-one
(19). Colorless oil, 69%. IRfilm: 2933, 2859, 1768, 1450,
1344, 1269, 1193, 1162, 1099, 1031; 1H NMR d: 4.68 (ddt,
J1Z9.2 Hz, J2Z6.9 Hz, J3Z4.7 Hz, 1H); 3.74 (d, JZ
4.7 Hz, 2H); 2.43 (dd, J1Z13.0 Hz, J2Z6.9 Hz, 1H); 1.90
13.5 Hz, J2Z8.5 Hz, J3Z7.3 Hz, 1H); 1.93–1.70 (m, 1H);
1.75 (d, JZ6.9 Hz, 3H); 1.50–1.32 (m, 5H); 0.95–0.85 (m,
3H); 13C NMR d: 179.0 (C); 80.0 (CH); 50.8 (CH); 39.3
(CH); 31.2 (CH2); 31.1 (CH2); 29.3 (CH2); 22.3 (CH2); 21.2
1
(CH3); 13.8 (CH3). Isomer B: H NMR d: 4.50–4.39 (m,
(dd, J1Z13.0 Hz, J2Z9.2 Hz, 1H); 1.85–1.20 (m, 10H); 13
C
1H); 4.28–4.12 (m, 1H); 2.75–2.43 (m, 2H); 1.96–1.81 (m,
1H); 1.75 (d, JZ6.9 Hz, 3H); 1.53–1.27 (m, 6H); 0.95–0.88
(m, 3H); 13C NMR d: 178.0 (C); 80.2 (CH); 49.0 (CH); 40.4
(CH); 31.8 (CH2); 29.6 (CH2); 29.1 (CH2); 22.1 (CH2); 21.0
(CH3); 13.6 (CH3).
NMR d: 180.4 (C); 75.1 (CH); 45.7 (CH2); 44.4 (C); 36.0
(CH2); 33.6 (CH2); 31.8 (CH2); 24.8 (CH2); 21.8 (CH2);
21.6 (CH2); HRMS (EI): MC, found 202.0760; C12H15ClO2
requires 202.0782; MS (EI) m/z: 202 (MC, 44%); 153
(35%); 147 (56%); 134 (82%); 81 (100%); 67 (58%).
3.3.16. 2-Butyl-4-(1-bromo-3-methylbutyl)-4-butanolide
(29). Colorless oil, 66%, obtained as a 1:1 mixture of cis-
and trans-isomers. Anal. Calcd for C13H23BrO2: C 53.61, H
7.96; found: C 53.32, H 7.84; IRfilm: 2958, 2868, 1773,
1462, 1362, 1267, 1173; HRMS (EI): MC, found 324.0736;
C16H21O2Br requires 324.0725. Isomer A: 1H NMR d: 4.61
(ddd, J1Z8.7 Hz, J2Z4.7 Hz, J3Z3.2 Hz, 1H); 4.12 (dt,
J1Z6.8 Hz, J2Z3.2 Hz, 1H); 2.89–2.73 (m, 1H); 2.38 (ddd,
J1Z13.0 Hz, J2Z10.0 Hz, J3Z4.6 Hz, 1H); 2.17–2.06 (m,
1H); 2.02–1.81 (m, 3H); 1.63–1.32 (m, 6H); 0.98–0.88 (m,
9H); 13C NMR d: 179.2 (C); 79.3 (CH); 56.6 (CH); 43.0
(CH2); 39.3 (CH); 31.5 (CH2); 31.3 (CH2); 29.3 (CH2); 25.9
(CH); 23.0 (CH3); 22.4 (CH2); 20.8 (CH3); 13.8 (CH3).
Isomer B: 1H NMR d: 4.47 (ddd, J1Z10.0 Hz, J2Z6.0 Hz,
J3Z4.0 Hz, 1H); 4.12 (dt, J1Z10.4 Hz, J2Z3.8 Hz, 1H);
2.74–2.41 (m, 2H); 2.02–1.78 (m, 4H); 1.63–1.34 (m, 6H);
0.99–0.89 (m, 9H); 13C NMR d: 178.0 (C); 79.4 (CH); 54.4
(CH); 42.6 (CH2); 40.4 (CH); 32.1 (CH2); 29.8 (CH2); 29.5
(CH2); 25.9 (CH); 23.1 (CH3); 22.4 (CH2); 20.7 (CH3); 13.8
(CH3).
3.3.13. 2-Isopropyl-4-chloromethyl-4-butanolide (20).
Colorless oil, 59%, obtained as a 1:1 mixture of cis- and
trans-isomers, bp 95 8C/0.8 mmHg. IRfilm: 2964, 2880,
1774, 1465, 1342, 1173, 1035; HRMS (EI): [MKCH3]C,
found 161.0355; C7H10ClO2 requires 161.0369 (the inten-
sity of MC ion was too low for a high resolution signal).
1
Isomer A: H NMR d: 4.77–4.61 (m, 1H); 3.71–3.68 (m,
2H); 2.71 (ddd, J1Z9.5 Hz, J2Z8.4 Hz, J3Z5.0 Hz, 1H);
2.29–2.06 (m, 3H); 1.04 (d, JZ6.8 Hz, 3H); 0.95 (d, JZ
6.6 Hz, 3H); 13C NMR d: 177.8 (C); 76.2 (CH); 46.4 (CH2);
45.0 (CH); 28.7 (CH); 26.5 (CH2); 20.1 (CH3); 18.1 (CH3).
Isomer B: 1H NMR d: 4.59 (ddd, J1Z11.2 Hz, J2Z6.1 Hz,
J3Z5.1 Hz, 1H)m, 1H); 3.72 (d, JZ5.0 Hz, 2H); 2.67 (ddd,
J1Z12.1 Hz, J2Z9.1 Hz, J3Z5.0 Hz, 1H); 2.35 (ddd, J1Z
12.1 Hz, J2Z9.1 Hz, J3Z6.2 Hz, 1H); 2.26–2.13 (m, 1H);
2.00–1.83 (m, 1H); 1.06 (d, JZ6.4 Hz, 3H); 0.94 (d, JZ
6.6 Hz, 3H); 13C NMR d: 176.9 (C); 75.9 (CH); 46.4 (CH2);
45.3 (CH); 27.5 (CH2); 27.4 (CH); 20.3 (CH3); 18.0 (CH3).
3.3.14. 2-(2-Phenylmethyl)-4-bromomethyl-4-butanolide
(21). Colorless oil, 54%, obtained as a 1:1 mixture of cis-
and trans-isomers, which were separated by column
chromatography. Spectroscopic data for this compound
have not been reported in the literature.22 IRfilm: 2923, 2862,
1777, 1604, 1496, 1341, 1161; HRMS (EI): MC, found
3.3.17. 2-Butyl-4-(1-bromo-2-cyclohexylethyl)-4-butano-
lide (30). Colorless oil, 54%, obtained as a 1:1 mixture of
diastereoisomers. IRfilm: 2923, 2858, 1751, 1449, 1351,
1272, 1181, 1117, 1064, 1032. Isomer A: 1H NMR d: 4.53–
4.41 (m, 1H); 4.16 (ddd, J1Z10.7 Hz, J2ZJ3Z3.6 Hz, 1H);
2.73–2.29 (m, 3H); 2.00–1.50 (m, 12H); 1.47–1.12 (m, 7H);
0.96–0.89 (m, 3H); 13C NMR d: 178.0 (C); 79.5 (CH); 57.7
(CH); 46.6 (CH2); 40.5 (CH); 35.1 (CH); 33.7 (CH2); 32.1
(CH2); 31.6 (CH2); 29.8 (CH2); 29.5 (CH2); 26.4 (CH2);
26.1 (CH2); 25.8 (CH2); 22.4 (CH2); 13.8 (CH3). Isomer B:
mp 82 8C. Anal. calcd. for C16H27BrO2: C 58.01, H 8.21;
found: C 57.65, H 8.18; 1H NMR d: 4.60 (ddd, J1Z8.6 Hz,
J2Z4.7 Hz, J3Z3.1 Hz, 1H); 4.21–4.11 (m, 1H); 2.88–2.73
(m, 1H); 2.39 (ddd, J1Z13.3 Hz, J2Z10.1 Hz, J3Z4.6 Hz,
1H); 2.09 (ddd, J1Z13.3 Hz, J2Z8.6 Hz, J3Z7.4 Hz, 1H);
1.95–1.51 (m, 10H), 1.45–1.11 (m, 9H); 0.95–0.85 (m, 3H);
13C NMR d: 179.1 (C); 79.3 (CH); 56.0 (CH); 41.7 (CH2);
39.3 (CH); 35.2 (CH); 33.6 (CH2); 31.7 (CH2); 31.5 (CH2);
31.3 (CH2); 29.3 (CH2); 26.4 (CH2); 26.1 (CH2); 25.9
(CH2); 22.5 (CH2); 13.8 (CH3).
1
268.0091; C13H13BrO2 requires 268.0099. Isomer A: H
NMR d: 7.37–7.17 (m, 5H); 4.54 (ddt, J1Z10.7 Hz, J2Z
J3Z5.2 Hz, 1H); 3.46 (d, JZ5.2 Hz, 2H); 3.23–3.02 (m,
1H); 2.92–2.72 (m, 2H); 2.26–2.14 (m, 2H); 13C NMR d:
178.2 (C); 138.1 (C); 128.8 (CH); 128.7 (CH); 126.8 (CH);
126.7 (CH); 76.1 (CH); 40.7 (CH); 36.4 (CH2); 34.0 (CH2);
30.7 (CH2). Isomer B: 1H NMR d: 7.37–7.18 (m, 5H); 4.54
(dddd, J1Z9.5 Hz, J2ZJ3Z6.2 Hz, J4Z4.5 Hz, 1H); 3.49
(dd, J1Z12.1 Hz, J2Z4.2 Hz, 1H); 3.38 (dd, J1Z12.1 Hz,
J2Z6.2 Hz, 1H); 3.28 (dd, J1Z12.0 Hz, J2Z4.6 Hz, 1H);
3.00 (dddd, J1Z11.4 Hz, J2ZJ3Z9.0 Hz, J4Z4.2 Hz, 1H);
3.23–3.02 (m, 1H); 2.79 (dd, J1Z12.1 Hz, J2Z9.0 Hz, 1H);
2.42 (ddd, J1Z13.1 Hz, J2Z9.0 Hz, J3Z6.2 Hz, 1H); 1.76
(ddd, J1Z13.1 Hz, J2Z11.4 Hz, J3Z9.5 Hz, 1H); 13C
NMR d: 177.1 (C); 138.1 (C); 128.8 (CH); 128.7 (CH);
126.8 (CH); 76.2 (CH); 42.5 (CH); 36.0 (CH2); 33.1 (CH2);
32.8 (CH2).
3.3.18. 2-(2-Phenylmethyl)-4-(1-bromo-3-methylbutyl)-
4-butanolide (31). Colorless oil, 21%, single isomer.
IRfilm: 3032, 2958, 2874, 1774, 1603, 1496, 1459, 1362,
1172, 1038; 1H NMR d: 7.37–7.10 (m, 5H); 4.39 (ddd, J1Z
8.2 Hz, J2Z5.2 Hz, J3Z3.2 Hz, 1H); 4.03 (ddd, J1ZJ2Z
7.0 Hz, J3Z3.2 Hz, 1H); 3.26–3.10 (m, 2H); 2.82 (dd, J1Z
15.0 Hz, J2Z10.0 Hz, 1H); 2.33–2.07 (m, 2H); 1.97–1.77
(m, 2H); 1.58–1.44 (m, 1H); 0.94 (d, JZ6.6 Hz, 3H); 0.87
(d, JZ6.6 Hz, 3H); 13C NMR d: 178.4 (C); 139.0 (C); 129.0
(CH); 128.8 (CH); 126.9 (CH); 79.3 (CH); 56.6 (CH); 43.1
3.3.15. 2-Butyl-4-(1-bromoethyl)-4-butanolide (28). Col-
orless oil, 73%, obtained as a 1:1 mixture of cis- and trans-
isomers. Anal. Calcd for C10H17BrO2: C 48.21, H 6.88;
found: C 47.71, H 6.98; IRfilm: 2958, 2931, 2865, 1779,
1
1452, 1355, 1220, 1171; Isomer A: H NMR d: 4.57 (ddd,
J1Z8.5 Hz, J2Z4.8 Hz, J3Z3.5 Hz, 1H); 4.20 (dq, J1Z
6.9 Hz, J2Z3.5 Hz, 1H); 2.83–2.70 (m, 1H); 2.34 (ddd, J1Z
13.5 Hz, J2Z10.0, J3Z4.1 Hz, 1H); 2.09 (ddd, J1Z

8964
V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
(CH2); 41.0 (CH); 37.0 (CH2); 30.6 (CH2); 25.9 (CH); 22.9
(CH3); 20.8 (CH3).
45.8; 40.5; 38.3; 37.0; 36.3; 35.0; 33.2; 33.1; 32.6; 32.3;
31.8; 30.5; 26.5; 21.1; 20.8; 16.4; 13.4.
3.3.22. 3-Methyl-2-oxaspiro[4.5]decane-1-one (36) and 4-
methyl-2-oxaspiro[4.5]decane-1-one (37). Mixture of
regioisomers in 2:1 ratio, obtained as a colorless oil in
35% yield. The regioisomers were separated by preparative
gas chromatography. Physical data for 3-methyl-2-oxaspir-
o(4.5(decane-1-one (36):23 White crystals, mp 70 8C; IR:
2930, 2859, 1756, 1452, 1391, 1212, 1135, 1086, 1015; 1H
NMR spectra identical to that reported in the literature;23
13C NMR d: 182.0 (C); 73.6 (CH); 45.3 (C); 41.1 (CH2);
34.3 (CH2); 31.5 (CH2); 25.3 (CH2); 22.1 (CH2); 22.0
(CH2); 21.4 (CH3). Physical data for 4-methyl-2-oxaspiro
3.3.19. 4-(1-Bromo-2-cyclohexylethyl)-2-isopropyl-4-
butanolide (32). Colorless oil, 69%, obtained as a 1:1
mixture of diastereoisomers, which were separated by dry-
flash chromatography. IRfilm: 2926, 2846, 1758, 1448, 1377,
1
1238, 1160, 1039. Isomer A: H NMR d: 4.55 (ddd, J1Z
7.6 Hz, J2Z6.0 Hz, J3Z3.0 Hz, 1H); 4.16 (ddd, J1ZJ2Z
6.6 Hz, J3Z3.5 Hz, 1H); 2.77 (ddd, J1ZJ2Z9.0 Hz, J3Z
5.0 Hz, 1H); 2.29–2.17 (m, 3H); 1.81–1.51 (m, 8H); 1.35–
1.12 (m, 3H); 1.02 (d, JZ6.9 Hz, 3H); 0.95 (d, JZ6.9 Hz,
3H); 0.91–0.75 (m, 2H); 13C NMR d: 178.3 (C); 79.4 (CH);
56.5 (CH); 45.4 (CH); 41.7 (CH2); 35.2 (CH); 33.6 (CH2);
31.7 (CH2); 29.2 (CH); 27.4 (CH2); 26.3 (CH2); 26.0 (CH2);
25.8 (CH2); 20.2 (CH3); 18.1 (CH3); HRMS (EI): MC,
found 316.1043; C15H25BrO2 requires 316.1038. Isomer B:
1H NMR d: 4.44 (ddd, J1Z10.1 Hz, J2Z6.1 Hz, J3Z
4.0 Hz, 1H); 4.18 (ddd, J1ZJ2Z7.4 Hz, J3Z3.5 Hz, 1H);
2.64 (ddd, J1Z12.2 Hz, J2Z9.0 Hz, J3Z5.0 Hz, 1H); 2.40–
2.15 (m, 2H); 2.10–1.53 (m, 9H); 1.42–1.11 (m, 3H); 1.05
(d, JZ7.0 Hz, 3H); 0.95 (d, JZ7.0 Hz, 3H); 0.89–0.72 (m,
2H); 13C NMR: 176.9 (C); 79.1 (CH); 53.7 (CH); 46.6 (CH);
41.4 (CH2); 35.1 (CH); 33.7 (CH2); 31.6 (CH2); 27.7 (CH2);
27.6 (CH); 26.4 (CH2); 26.1 (CH2); 25.8 (CH2); 20.5 (CH3);
18.3 (CH3); HRMS (EI): MC, found 316.1053; C15H25BrO2
requires 316.1038.
1
(4.5(decane-1-one (37):24 Colorless oil; IR and H NMR
spectra identical to that reported in the literature;24 13C
NMR spectra for this compound have not been reported in
the literature;13C NMR d: 181.2 (C); 71.5 (CH2); 45.1 (C);
38.3 (CH); 31.9 (CH2); 27.2 (CH2); 25.4 (CH2); 21.9 (CH2);
21.6 (CH2); 13.5 (CH3).
3.3.23. 2,2,4-Trimethyl-4-butanolide (38) and 2,2,3-tri-
methyl-4-butanolide (39). Mixture of regioisomers in 3:2
ratio, obtained as a colorless oil in 38% yield. The
regioisomers were separated by preparative gas chromatog-
raphy. Physical data for 2,2,4-trimethyl-4-butanolide (38):25
White crystals, mp 53 8C; IR: 2975, 2938, 2878, 1766, 1459,
1387, 1186, 1112; 1H NMR spectra identical to that reported
in the literature;25 13C NMR d: 182.1; 73.3; 45.2; 40.8; 25.0;
24.3; 21.1. Physical data for 2,2,3-trimethyl-4-butanolide
(39):26 Colorless oil; Spectroscopic data for this compound
have not been reported in the literature;26IRfilm: 2971, 2923,
3.3.20. 3-Butylhexahydrobenzofuran-2-one (33). Color-
less oil, 48%, obtained as a 1:1 mixture of stereoisomers
which were separated by preparative gas chromatography.
HRMS (EI): MC, found 196.1463; C12H20O2 requires
196.1482; MS (EI) m/z: 196 (MC; 8%); 140 (100%); 95
(8%); 82 (6%); 67 (9%); IRfilm: 2937, 2864, 1777, 1457,
1389, 1206, 1175, 1124, 1080, 1024. Isomer A: 1H NMR d:
3.70 (ddd, J1ZJ2Z10.8 Hz, J3Z3.8 Hz, 1H); 2.30–2.15
(m, 2H); 2.10–1.70 (m, 4H); 1.65–1.20 (m, 10H); 0.91 (t,
JZ7.0 Hz, 3H); 13C NMR d: 178.6; 82.6; 49.9; 46.2; 30.1;
29.2; 28.2; 28.1; 25.3; 24.0; 22.8; 13.9. Isomer B: 1H NMR
d: 3.97 (ddd, J1ZJ2Z10.8 Hz, J3Z4.0 Hz, 1H); 2.50–2.40
(m, 1H); 2.30–2.10 (m, 1H); 2.00–1.80 (m, 4H); 1.60–1.20
(m, 10H) 0.91 (t, JZ7.0 Hz, 3H); 13C NMR d: 175.0; 82.0;
47.7; 44.0; 30.7; 29.6; 25.4; 25.0; 24.7; 23.9; 22.6; 13.9.
1
1775, 1462, 1393, 1220, 1109; H NMR d: 4.37 (dd J1Z
9.0 Hz, J2Z7.5 Hz, 1H); 3.80 (dd, J1ZJ2Z9.0 Hz, 1H);
2.33 (ddq, J1Z9.5 Hz, J2ZJ3Z7.0 Hz, 1H); 1.25 (s, 3H);
1.09 (s, 3H); 1.05 (d, JZ7.0 Hz, 3H); 13C NMR d: 182.6;
71.1; 41.4; 40.6; 23.2; 17.9; 11.1.
3.3.24. 2,2-Dimethyl-3-phenyl-4-butanolide (40). Color-
less oil, 15% yield. When the reaction was performed by
substituting BF3$Et2O for TiCl4, the title compound was
isolated in 32% yield. Spectroscopic data for this compound
have not been reported in the literature.27 IRfilm: 3032, 2977,
2915, 2876, 1774, 1595, 1492, 1457, 1393, 1207, 1108,
1
1029; H NMR d: 7.40–7.15 (m, 5H); 4.56 (dd, J1ZJ2Z
8.0 Hz, 1H); 4.50 (dd, J1ZJ2Z8.0 Hz, 1H); 3.42 (dd, J1Z
J2Z8.0 Hz, 1H); 1.35 (s, 3H); 0.90 (s, 3H); 13C NMR d:
181.5 (C); 136.0 (C); 128.7 (CH); 128.0 (CH); 127.4(CH);
68.6 (CH2); 52.1 (CH); 24.1 (CH3); 19.6 (CH3).
3.3.21. 2-(2-Phenylethyl)-4-methyl-4-butanolide (34) and
2-(2-phenylethyl)-3-methyl-4-butanolide (35). Colorless
oil, 30% (41% yield calculated on the basis of the recovered
starting compound), obtained as a mixture of regioisomers
in a 7:3 ratio (regioisomer 34 as 1:1 mixture of
diastereoisomers; regioisomer 35 as 3:1 mixture of
diastereoisomers). Anal. Calcd for C13H16O2: C 76.44, H,
7.90; found: C 76.26; H 8.09; IRfilm: 3028, 2975, 2932,
3.4. General procedure for the reduction of 4-(1-halo-
alkyl)-4-butanolides with tributyltin hydride
1
1769, 1603, 1496, 1454, 1185; HNMR d: 7.47–7.16 (m,
A solution of the corresponding 4-(1-haloalkyl)-4-butano-
lide (1 mmol), tributyltin hydride (1.5 mmol) and a catalytic
amount of azobis(isobutyronitrile) in benzene (5 mL) was
heated to reflux, with stirring, under an argon atmosphere.
The course of the reaction was monitored by TLC. Upon
completion, the reaction mixture was concentrated under
reduced pressure, dissolved in diethyl ether (20 mL), a
saturated aqueous solution of sodium fluoride (10 mL) was
added and the mixture was vigorously stirred for 24 h at rt.
The organic layer was separated, dried over anh. Na2SO4,
5H); 4.67 (ddq, J1Z12.7 Hz, J2ZJ3Z6.3 Hz, 1H, 34,
isomer A); 4.45 (ddq, J1Z11 Hz, J2Z6.2 Hz, J3Z5.5 Hz,
1H, 34, isomer B); 4.36 (dd, J1Z8.8 Hz, J2Z7.0 Hz, 1H,
35, isomer A); 3.69 (dd, J1ZJ2Z6.4 Hz, 1H, 35, isomer B);
2.85–2.40 (m, 4H); 2.30–1.90 (m, 2H); 1.85–1.58 (m, 1H);
1.41 (d, JZ6.3 Hz, 3H, 34, isomer A); 1.35 (d, JZ6.2 Hz,
3H, 34, isomer B); 1.13 (d, JZ6.4 Hz, 3H, 35, isomer B);
1.04 (d, JZ7.0 Hz, 3H, 35, isomer A); 13C NMR d: 179.1;
178.8; 140.7; 128.5; 128.4; 126.1; 75.0; 74.8; 73.0; 72.4;

V. Maslak et al. / Tetrahedron 60 (2004) 8957–8966
8965
filtered, concentrated under reduced pressure and the
product was purified by dry-flash chromatography.
compound 34, whose physical data are given in Section
3.4.1.
3.4.1. 2-(2-Phenylethyl)-4-methyl-4-butanolide (34). Col-
orless oil, 73%, obtained from 14 as a 1:1 mixture of
diastereoisomers. Spectroscopic data for this compound
have not been reported in the literature.28 IRfilm: 3059, 3028,
2978, 2931, 1769, 1604, 1453, 1350, 1186, 1113; 1H NMR
d: 7.32–7.13 (m, 5H); 4.63 (ddq, J1Z12.7 Hz, J2ZJ3Z
6.3 Hz, 1H, isomer A); 4.41 (ddq, J1Z11.0 Hz, J2Z6.2 Hz,
J3Z5.5 Hz, 1H isomer B); 2.75–2.36 (m, 4H); 2.31–1.90
(m, 2H); 1.83–1.61 (m, 1H); 1.38 (d, JZ6.2 Hz, 3H isomer
A); 1.35 (d, JZ6.3 Hz, 3H, isomer B); 13C NMR d: 178.9
(C); 178.6 (C); 140.6 (C); 128.2 (CH); 128.1 (CH); 125.9
(CH); 74.8 (CH); 74.7 (CH); 40.3 (CH); 38.2 (CH); 36.8
(CH2); 34.7 (CH2); 33.1 (CH2); 33.0 (CH2); 32.1 (CH2);
31.7 (CH2); 20.9 (CH3); 20.6 (CH3).
3.6. Allylation of 4-bromomethyl-2-butyl-4-butanolide
(16) with allyl tributyltin. 4-(3-Butenyl)-2-butyl-4-
butanolide (44)
A
solution of 4-bromomethyl-2-butyl-4-butanolide
(116 mg; 0.49 mmol), allyl tributyltin (326 mg;
0.99 mmol) and azobis(isobutyronitrile) (catalytic amount)
in benzene (1 mL) was heated to reflux, with stirring, under
an argon atmosphere. The reaction was monitored by TLC.
Work-up of the reaction mixture as described in Section
3.4., followed by purification by dry-flash chromatography,
afforded 80 mg (83%) of the title compound 44, as a
colorless oil. Anal. calcd. for C12H20O2: C 73.43, H 10.27;
found: C 73.63, H 10.61; IRfilm: 2933, 2866, 1771, 1458,
1357, 1287, 1178; 1H NMR d: 5.81 (ddt, J1Z17.0 Hz, J2Z
10.3 Hz, J3Z6.6 Hz, 1H); 5.12–4.99 (m, 2H); 4.51 (ddt,
J1Z7.9 Hz, J2ZJ3Z6.2 Hz, 1H); 2.67–2.52 (m, 1H); 2.31–
1.98 (m, 4H); 1.92–1.55 (m, 4H); 1.49–1.27 (m, 6H); 0.92
(t, JZ7.6 Hz, 3H); 13C NMR d: 172.4 (C); 137.1 (CH);
115.6 (CH2); 78.0 (CH); 39.2 (CH); 34.8 (CH2); 33.4 (CH2);
30.5 (CH2); 29.5 (CH2); 29.4 (CH2); 22.4 (CH2); 13.9
(CH3).
3.4.2. 2-Butyl-4-methyl-4-butanolide (41). Colorless oil,
74%, obtained from 15 as a 1:1 mixture of diastereoisomers.
Spectroscopic data for this compound have not been
reported in the literature.28 IRfilm: 2961, 2933, 2865, 1772,
1
1460, 1346, 1179. H NMR d: 4.67 (ddq, J1ZJ2ZJ3Z
6.4 Hz, 1H, isomer A); 4.49 (ddq, J1Z11.0 Hz, J2ZJ3Z
6.0 Hz, 1H isomer B); 2.70–2.43 (m, 1.5H); 2.11–1.76 (m,
2H); 1.56–1.27 (m, 5.5H); 1.42 (d, JZ6.0 Hz, 3H isomer
B); 1.37 (d, JZ6.4 Hz, 3H, isomer A); 0.95–0.88 (m, 3H);
13C NMR d: 179.3 (C); 179.0 (C); 74.9 (CH); 74.8 (CH);
41.2 (CH); 39.1 (CH); 36.8 (CH2); 34.8 (CH2); 30.2 (CH2);
29.8 (CH2); 29.3 (CH2); 22.2 (CH2); 21.0 (CH3); 20.7
(CH3); 13.6 (CH3).
3.7. Tributyltin hydride mediated free radical addition
of 4-bromomethyl-2-butyl-4-butanolide (28) to
acrylonitrile. 4-(4-Cyano-2-butyl)-2-butyl-4-butanolide
(45)
To a refluxing solution of 4-bromomethyl-2-butyl-4-buta-
nolide 28A (120 mg; 0.48 mmol), acrylonitrile (510 mg;
9.6 mmol) and azobis(isobutyronitrile) (catalytic amount) in
benzene (24 mL), tributyltin hydride (9 mL of 0.07 M
solution in benzene; 0.63 mmol) was added in 4 portions,
in 30 min intervals, with stirring, under an argon atmos-
phere. The reaction was monitored by TLC. Work-up of the
reaction mixture as described in Section 3.4, followed by
purification by dry-flash chromatography, afforded 82 mg
(76%) of the title compound 45, as a colorless oil (obtained
as 1:1 mixture of diastereoisomers). IRfilm: 2961, 2935,
3.4.3. 3-Methyl-2-oxa-spiro[4.5]decane-1-one (36). White
crystals, mp 70 8C, 78%. The spectra of 36 are given in
Section 3.3.22.
3.4.4. 2-(2-Phenylmethyl)-4-methyl-4-butanolide (42).
From 21A. Colorless oil, 80%. Spectroscopic data identical
to that reported in the literature.20,29
3.4.5. 2-Butyl-4-ethyl-4-butanolide (43). From 28A.
Colorless oil, 82%. Spectroscopic data for this compound
have not been reported in the literature.30 IRfilm: 3050, 2960,
1
2870, 2247, 1769, 1463, 1183, 1001; H NMR: 4.46–4.36
1
(m, 1H, isomer A); 4.22 (dd, J1Z15.3 Hz, J2Z6.9 Hz, 1H,
isomer B); 2.70–2.55 (m, 1H); 2.53–2.36 (m, 2H); 2.24–
1.97 (m, 3H); 1.92–1.75 (m, 3H); 1.67–1.27 (m, 5H); 1.00
(t, JZ6.3 Hz, 3H); 0.95–0.88 (m, 3H); 13C NMR: 179.2 (C);
179.0 (C); 119.4 (C); 119.2 (C); 82.0 (CH); 80.8 (CH); 39.5
(CH); 39.4 (CH); 37.3 (CH); 36.6 (CH); 31.6 (CH2); 30.8
(CH2); 30.7 (CH2); 30.6 (CH2); 29.3 (CH2); 28.6 (CH2);
28.0 (CH2); 22.3 (CH2); 14.9 (CH2); 14.8 (CH2); 14.4
(CH3); 13.7 (CH3); 13.2 (CH3); HRMS (EI): MC, found
223.1564; C13H21NO2 requires 223.1572.
2928, 1770, 1461, 1357, 1180. H NMR d: 4.50–4.21 (m,
1H); 2.67–2.37 (m, 1H); 2.12–2.01 (m, 2H); 1.93–1.27 (m,
8H); 1.04–0.89 (m, 6H); 13C NMR d: 178.0 (C); 80.0 (CH);
39.3 (CH); 33.0 (CH2); 30.6 (CH2); 29.5 (CH2); 28.5 (CH2);
22.4 (CH2); 13.9 (CH3); 9.6 (CH3).
3.5. Reduction of 4-bromoalkyl-4-butanolides with
hypophosphorous acid. 2-(2-Phenylethyl)-4-methyl-4-
butanolide (34)
To a refluxing solution of 14 (150 mg; 0.53 mmol),
hypophosphorous acid (289 mL of the 50% aqueous
solution; 2.65 mmol) and triethylamine (295 mg;
2.92 mmol) in dioxane (4.8 mL) was added AIBN
(113 mg; 0.7 mmol) in four portions, at 30 min intervals.
Upon completion, the reaction mixture was diluted with
dichloromethane (50 mL) and washed with water. The
organic extract was dried over anh. MgSO4, filtered and
concentrated under reduced pressure. Purification by dry-
flash chromatography afforded 82 mg (76%) of the title
Acknowledgements
ˇ
ˇ
´
We dedicate this work to Professor Zivorad Cekovic, with
the sentiments of gratitude and respect, on the occasion of
his 70th birthday. This work was financially supported by
the Ministry of science, technology and development
(Project N8 1719). Part of the research was performed at
the Free University of Berlin. One of us (V. M.) is grateful

8966
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10. Movassaghi, M.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124,
2456–2457.
to Professor Hans-Ulrich Reissig for helpful discussions and
his interest in this work, and to Mrs. Ivana Veljkovic for
recording HRM spectra of several samples. The authors
gratefully acknowledge the support of Professor Ernst-
Walter Knapp and the D. A. A. D. foundation.
11. (a) Lalic, G.; Petrovski, Z.; Galonic, D.; Matovic, R.; Saicic,
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Ed. Engl. 2000, 39, 4343–4346.
12. Lalic, G.; Petrovski, Z.; Galonic, D.; Matovic, R.; Saicic,
R. N. Tetrahedron 2001, 57, 583–591.
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