Atom Transfer Radical Cyclisations Mediated by the Grubbs Ruthenium Metathesis Catalyst

Article abstract of DOI:10.1055/s-2003-41466

The commercially available ruthenium carbene complex RuCl ₂(=CHPh)(PCy₃)₂ efficiently catalyses the cychsation of halo alkenes to γ-lactones and γ-lactams.

Full text of DOI:10.1055/s-2003-41466

LETTER
1797
Atom Transfer Radical Cyclisations Mediated by the Grubbs Ruthenium
Metathesis Catalyst
Atom
T
ransfe
r
e
Radica
l
C
t
e
ons r Quayle,*a David Fengas,a Stuart Richardsb
a
Department of Chemistry, University of Manchester, Manchester M13 9PL, UK
Fax +44(161)2754939; E-mail: peter.quayle@man.ac.uk
b
Zeneca Specialties, Blackley, Manchester, UK
Received 16 July 2003
Cl
Cl
H
Abstract: The commercially available ruthenium carbene complex
RuCl2(=CHPh)(PCy3)2 efficiently catalyses the cyclisation of halo
alkenes to g-lactones and g-lactams.
O
Cu(bipy)Cl
MeCN
Cl
O
Ph
Ph
O
CCl3
O
1
Keywords: carbene complexes, free radicals, metathesis, lactones,
lactams
2
Scheme 1
In recent years cyclisation reactions involving carbon-
centred radicals have proved to be highly effective for the
synthesis of a large variety of carbocyclic and hetero-
cyclic systems.1 The generality of this methodology
results, in part, from their predictable stereochemical out-
come, especially for the synthesis of 5- and 6-membered
rings,2 coupled with the high degree of functional group
compatibility often associated with free radical
processes.3 Major limitations of the ubiquitous tin
hydride-based methodology4 result from the generation of
an inert carbon-hydrogen bond in the termination step of
the cycle and the use of stochiometric quantities of tin
reagents. Reactions which reintroduce a carbon-halogen
(or pseudohalogen) bond in the termination step, so called
Atom Transfer Cyclisation Reactions (ATCR),5 are of
interest in that the initial cyclised product can be utilised
in subsequent synthetic transformations6 and benefits
from the use of a catalytic halogen transfer agent. Whilst
chemistry. Unfortunately our initial attempts to cyclise 1
using the conventional Cu-2,2¢-bipyridine catalyst in
acetonitrile, as described by Nagashima,9,10 afforded only
trace amounts of the desired product 2. Given that this
catalyst system appeared to have a limited solubility range
we decided to screen catalysts, which have a greater solu-
bility in the solvent systems usually employed in free
radical reactions.
PCy3
Cl
Ru
Cl
Ph
PCy3
Cl
3
Cl2HC
R
R
Scheme 2
At this point we were intrigued by a recent study by
Snapper et al16 in which the well defined Grubbs metathe-
sis catalyst 3 was found to act as a promoter for intermo-
lecular Kharasch reaction of chloroform with alkenes
(Scheme 2). Contemporaneously Demonceau et al17a,b and
latterly Grubbs17c–17f reported that the catalyst 3 was also
effective in promoting ATRP reactions of vinyl
monomers. In this Letter we wish to present our
preliminary findings on the efficacy of the Grubbs catalyst
3 in intramolecular Kharasch type reactions leading to the
synthesis of g-lactones and g-lactams.
atom transfer reactions have recently enjoyed
a
considerable renaissance in polymer chemistry (Atom
Transfer Radical Polymerisation Reactions, ATRP),7
applications of Kharasch-type reactions in organic
synthesis have been less evident.8
Nagashima9,10 first reported that treatment of substrates
such as 1 with CuCl in the presence of 2,2¢-bipyridine
furnished g-lactones in moderate yields (Scheme 1).
Subsequently numerous copper-amine complexes11 have
been proffered for use in such reactions, including the de-
velopment of solid-supported systems.12 A range of
transition metal complexes other than those of copper,
Cyclisation of ester- and amide-derived radicals such as 4
and 5 are subject to stereoelectronic factors18 where the
preference for the more stable yet unreactive s-cis rotamer
4c of esters often results in low yields of cyclised product.
In the case of amides the incorporation of a bulky N-
substituent generally favours the reactive s-trans rotamer
5t, a situation that is reflected in the higher yields of
cyclised products observed with these substrates,19
(Scheme 3).
14
15
including RuCl2(PPh3)3,13 RhCl(PPh3)3 and Fe(CO)5
have also been used as catalysts in these reactions.
During the course of another investigation we required a
procedure for the synthesis of g-lactones and g-lactams,
which in principle could be prepared using ATRC
SYNLETT 2003, No. 12, pp 1797–1800
2
9
.0
9
.2
0
0
3
We were gratified (Table 1, entry 1) to find therefore that
Advanced online publication: 19.09.2003
DOI: 10.1055/s-2003-41466; Art ID: D19003st.pdf
© Georg Thieme Verlag Stuttgart · New York
treatment20 of the cinnamyl ester 1 with a catalytic

1798
P. Quayle et al.
LETTER
R
Table 1 Treatment of the Cinnamyl Ester 1 with 3
Cl
Entry Substrate
Producta
Yieldb
54%c
Cl
O
R
O
Cl
Cl
Cl
Cl
1
O
Cl
Cl
H
O
O
4t
Ph
O
CCl3
Cl
O
Ph
Ph
4c
1
R
O
2
Cl
R'
N
Cl
2
25%c
Cl
R
O
N
Cl
H
R'
CCl3
O
Cl
O
O
O
5t
5c
Ph
O
Ph
Ph
7
Scheme 3
6
3
45%
75%
Cl
CCl3
Cl
O
Cl
quantity of 3 (5 mol%) in refluxing toluene (3 h) afforded
the isomerically pure g-lactone 221 in 54% isolated yield.
The stereochemical outcome of this reaction was secured
by x-ray crystallography. Similarly, treatment of the ester
6 to the same reaction conditions led to the formation of a
cyclised product 7, again as a single diastereoisomer,22
albeit in somewhat diminished yield (25%). Cyclisation of
the simple allyl ester 8 (entry 3), a notoriously poor sub-
strate in these cyclisation reactions, also proved effective
affording the lactone 99,10 in 45% isolated yield. Cyclisa-
tion of the cyclohexenyl ester 10 (entry 4) proceeded
slightly differently than anticipated, resulting in the
isolation of the unsaturated lactone 11 in 75% yield. Lac-
tone 11 was readily dehalogenated23 (Zn/AcOH; 85%) to
the known compound 12.24 The use of conjugated dienes
in ATRC reactions25 is also feasible using carbene 1 as a
catalyst as demonstrated by the cyclisation of the sorbyl
ester 13 to the lactone 14. Lactone 14 was isolated as a
single diastereoisomer in 46% yield. Our tentative
stereochemical assignment in this instance is based on
analogy with that observed in the cyclisation of 1 and 6.
O
O
8
O
9
4
Cl
O
O
H
Cl
O
CCl3
O
H
11
10
O
5
6
46%
Cl
H
Cl
major
O
CCl3
productd
Cl
O
13
O
14
70%
Cl
CCl3
Cl
Cl
N
O
Ts
N
Ts
O
15
16
7
0%
con-
version
S.M re-
covered.
Cl
O
Cl
H
The participation of amides in ATRC reactions is
generally found to be a relatively facile process19 and our
results bear out this generalisation, with two notable
exceptions (Table 1, entry 7). Curiously whilst cyclisation
of the amide 15 to the lactam 16 proceeded cleanly,
attempted cyclisation of the related substrates 17 and 18
merely resulted in the decomposition of the starting
material. The effect of a chiral auxiliary26 in these
cyclisations was investigated in the case of the readily
available amides 20 and 23 (Scheme 4).27 Whilst the in-
corporation of the N-camphorsulfonyl substituent has
little effect on the chemical conversion to the desired lac-
tams 21 and 24 (80% and 82% yield respectively), it is ob-
vious that subtle steric/electronic factors are operative.
Hence cyclisation of the alcohol 21 proceeded with no de-
tectable asymmetric induction whereas cyclisation of the
ketone 20 occurred with modest levels of asymmetric
induction (ca. 33% de) (Scheme 5).
Cl
RN
CCl3
O
N
H
H
17, R=H; 18, R=Ts
a Substrate and catalyst 3 (5 mol%) dissolved in degassed toluene and
brought to reflux for 3.5 h under argon.
b Refers to isolated yield after chromatography.
c Product stereochemistry determined by x-ray crystallography.
d Stereochemistry by analogy.
O
O
CCl3
Cl
Cl
i
ii
O
O
O
O
In conclusion we have demonstrated that the Grubbs
metathesis catalyst 3 can be used to promote atom transfer
radical cyclisation reactions. It should be noted that, in
comparison to other catalysts used in intramolecular
10
12
11
Scheme 4 i) (5 mol%), Toluene, 120 °C; ii) Zn/HOAc
Synlett 2003, No. 12, 1797–1800 © Thieme Stuttgart · New York

LETTER
Atom Transfer Radical Cyclisations
1799
(3) Fossey, J.; Lefort, D.; Sorba, J. Free Radicals in Organic
Chemistry; Wiley: New York, 1995.
(4) Baguley, P. A.; Walton, J. C. Angew. Chem., Int. Ed. 1998,
37, 3072.
(5) (a) Curran, D. P. Synthesis 1988, 417. (b) Curran, D. P.
Synthesis 1988, 489.
allylamine, Et3N
CH2Cl2
1.2 equiv nBuLi, THF
1.1 equiv CCl3COCl
O
O
SO2Cl
SO2NH
(6) For related applications in polymer chemistry see:
Matyjaszewski, K. Chem.-Eur. J. 1999, 5, 3095.
(7) Gaynor, S.; Qiu, J.; Matyjaszewski, K. ACS Symposium
Series 2002, 823, 113.
19
(8) See: Clark, A. J. Chem. Soc. Rev. 2002, 31, 1.
(9) Nagashima, H.; Wakamatsu, H.; Itoh, K.; Tomo, Y.; Tsuji,
J. Tetrahedron Lett. 1983, 24, 2395.
(10) Nagashima, H.; Wakamatsu, H.; Nobuyasu, O.; Tsutomu, I.;
Watanabe, M.; Tajima, T.; Itoh, K. J. Org. Chem. 1992, 57,
1682.
(11) (a) De Campo, F.; Lastecoueres, D.; Verlhac, J. J. Chem.
Soc., Perkin Trans. 1 2000, 575. (b) Clark, A. J.; Battle, G.
M.; Heming, A. M.; Haddleton, D. M.; Bridge, A.
Tetrahedron Lett. 2001, 42, 2003.
(12) (a) Clark, A. J.; Filik, R. P.; Haddleton, D. M.; Radigue, A.;
Sanders, C. J.; Thomas, G. H.; Smith, M. E. J. Org. Chem.
1999, 64, 8954. (b) Shen, Y.; Zhu, S.; Pelton, R.
Macromolecules 2001, 34, 3182.
(13) (a) Nagashima, H.; Ara, K.-I.; Wakamatsu, H.; Itoh, K. J.
Chem. Soc., Chem. Commun. 1985, 518. (b) For modified
Ru catalysts see: Nagashima, H.; Gondo, M.; Masuda, S.;
Kondo, H.; Yamaguchi, Y.; Matsubara, K. Chem. Commun.
2003, 442.
(14) Nagashima, H.; Seki, K.; Ozaki, N.; Wakamatsu, H.; Itoh,
K.; Tomo, Y.; Tsuji, J. J. Org. Chem. 1990, 55, 985.
(15) (a) Lee, G. M.; Parvez, M.; Weinreb, S. M. Tetrahedron
1988, 44, 4671. (b) Terent’ev, A. B.; Vasil’eva, T. T.;
Kuz’mina, N. A.; Ikonnikov, N. S.; Orlova, S. A.; Mysov, E.
I.; Belokon, Y. N. Russ. Chem. Bull. 1997, 46, 2096.
(16) Tallarico, J. A.; Malnick, L. M.; Snapper, M. L. J. Org.
Chem. 1999, 64, 344.
3, 5 mol%
PhMe
O
Cl
O
SO2N
SO2N
H
CCl3
O
Cl
20
O
Cl
21
NaBH4
MeOH
1.2 equiv nBuLi, THF
1.1 equiv CCl3COCl
19
OH
SO2NH
22
OH
Cl
H
OH
SO2N
3, 5 mol%
PhMe
SO2N
CCl3
O
Cl
O
Cl
23
24
Scheme 5
(17) (a) Simal, F.; Demonceau, A.; Noels, A. F. Tetrahedron Lett.
1999, 40, 5689. (b) Simal, F.; Delfosse, S.; Demonceau, A.;
Noels, A. F.; Denk, K.; Kohl, F. J.; Weskamp, T.; Herrmann,
W. A. Chem.–Eur. J. 2002, 8, 3047. (c) Bielawski, C. W.;
Louie, J.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122,
12872. (d) For an overview of the use of Grubbs catalyst in
non-metathesis reactions see: Alcaide, B.; Almendros, P.
Chem.–Eur. J. 2003, 9, 1258. (e) For mechanistic insights
see: Amir-Ebrahimi, V.; Hamilton, J. G.; Nelson, J.;
Rooney, J. J.; Rooney, A. D.; Harding, C. J. J. Organomet.
Chem. 2000, 606, 84–87. (f) Amir-Ebrahimi, V.; Hamilton,
J. G.; Nelson, J.; Rooney, J. J.; Thompson, J. M.; Beaumont,
A. J.; Rooney, A. D.; Harding, C. J. Chem. Commun. 1999,
1621.
Karasch reactions, low catalyst loadings (ca. 5 mol%) are
sufficient in order to effect good chemical conversions.28
Efforts are currently being directed towards the
identification of more effective chiral auxiliaries for these
reactions. Synthetic applications are also in progress.
Acknowledgement
We thank the EPSRC and Zeneca for the provision of a CASE
award (DF).
(18) Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima, K.;
Omoto, K.; Fujimoto, H. J. Am. Chem. Soc. 2000, 122,
11041.
(19) Note that the effect of temperature on reactive rotamer
population should not be forgotten in these cyclisation
reactions, see: Curran, D. P.; Tamine, J. J. Org. Chem. 1991,
56, 2746.
(20) Cyclisation of Ester 10 to Lactone 11 Using Catalyst 3 is
Representative: A dry flask was charged with the Grubbs
catalyst 3 (169.7 mg, 5 mol%, Strem) and toluene (5 mL).
The contents of the flask were degassed (three times using
freeze-thaw cycle) to which was added, by syringe, a
solution of the trichloroacetate 10 (1.0 g, 4.12 mmol) in
toluene (3 mL). After degassing (three times, freeze-thaw
cycle) the reaction mixture was brought to a gentle reflux
under argon for 3.5 h. The toluene was removed under
References
(1) (a) Bowman, W. R.; Cloonan, M. R.; Krintel, S. L. J. Chem.
Soc., Perkin Trans 1 2001, 2885. (b) Robertson, J.;Pillai, J.;
Lush, R. K. Chem. Soc. Rev. 2001, 30, 94. (c) Cossy, J.
Recent Res. Dev. Synth. Org. Chem. 1999, 2, 23.
(d) Bowman, W. R.; Bridge, C. F.; Brookes, P. J. Chem.
Soc., Perkin Trans 1 2000, 1. (e) Banik, B. K. Curr. Org.
Chem. 1999, 3, 469. (f) Giese, B.; Kopping, B.; Gobel, T.;
Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach, F. Org.
React. 1996, 48, 301.
(2) (a) Curran, D. P.; Porter, N. A.; Giese, B. In Stereochemistry
of Radical Reactions: Concepts, Guidelines and Synthetic
Applications; VCH: Weinheim, 1995. (b) Rajan Babu, T. V.
Acc. Chem. Res. 1991, 24, 139.
Synlett 2003, No. 12, 1797–1800 © Thieme Stuttgart · New York

1800
P. Quayle et al.
LETTER
reduced pressure and the crude product chromatographed
(‘flash’ silica, eluent: 10% EtOAc–petroleum ether) to
afford the lactone 11 as a white solid (mp 56–58 °C) in 75%
yield. 1H NMR (300 MHz, CDCl3) d: 2.2 (2 H, m, CH2), 2.4
(2 H, m, CH2), 2.95 (1 H, dt, J = 13, 4.4 Hz), 5.1 (1 H, t, J =
4.4 Hz), 6.0 (1 H, m, olefin), 6.3 (1 H, m, olefin). 13C NMR
(75 MHz, CDCl3) d: 167.1, 136.2, 121.0, 82.9, 60.3, 50.44,
23.8, 21.7. IR (cm–1, CHCl3): 1793, 1755. m/e (CI) 224
(100%) (M + NH4)+, 190 (45%). HRMS: C8H8O235Cl2,
calcd: 205.9901; found: 205.9901.
afford the sulfonamide 19 in 90% yield as a yellow solid (mp
50–51 °C). This material was sufficiently pure to be used
directly in the next step. 1H NMR (300 MHz, CDCl3) d
(ppm): 0.95 (3 H, s, Me), 1.05 (3 H, s, Me), 2.0–2.4 (7 H, m),
2.95 (1 H, d, J = 15.1 Hz, CH2SO), 3.4 (1 H, d, J = 15.1 Hz,
CH2SO), 3.85 (2 H, m, CH2CH=CH2), 5.25 (2 H, m,
CH=CH2), 5.95 (1 H, m, CH=CH2). 13C NMR (75 MHz,
CDCl3) d (ppm): 216.9, 133.6, 117.6, 59.1, 50.2, 50.2, 48.7,
46.1, 46.0, 42.8, 26.9, 26.6, 19.8, 19.4. IR (cm–1, CHCl3):
3290, 2960, 1741. m/e (CI) 289 [(M + NH4)+, 100%], 272
(100%), 215 (80%). HRMS: C13H22O3SN, (M + H)+ calcd:
272.1320; found: 272.1320. The sulfonamide 19 (2.0 g, 7.38
mmol) was dissolved in methanol (20 mL) to which was
added sodium borohydride (0.3 g, 1.0 equiv) and the
resulting solution left to stir at 0 °C until all the starting
material had been consumed (TLC). The reaction mixture
was concentrated in vacuo and partitioned between water
(150 mL) and Et2O (5 × 50 mL). The organic extracts were
dried (MgSO4), concentrated in vacuo and the residue
chromatographed (‘flash’ silica; eluent: 20% EtOAc–
petroleum ether) to afford the alcohol 22 as a viscous oil
(95% yield). 1H NMR (300 MHz, CDCl3) d (ppm): 0.8 (3 H,
s, Me), 1.0 (3 H, s, Me), 1.4–1.8 (7 H, m), 2.9 (1 H, d, J =
13.7 Hz, CH2SO), 3.16 (1 H, d, J = 8.7 Hz, OH), 3.4 (1 H, d,
J = 13.7 Hz, CH2SO), 3.85 (2 H, t, J = 6.0 Hz, CH2CH=CH2),
4.1 (1 H, dd, J = 4.1, 7.7 Hz, CH-OH), 4.4 (1 H, bt, J = 6.0
(21) The cyclisation of 1 was reported by Nagashima9 to be
highly diastereoselective although a stereochemical
assignment was not made.
(22) Stereochemical assignment is based on a single crystal x-ray
diffraction study. Crystal data for 2: C11H9Cl3O2, Mr =
279.53, orthorhombic, a = 8.737(2), b = 18.214(3), c =
7.5929(4), V = 1198.2(4) Å3, T = 296.2 K, space group P2121,
Z = 4, CuKa radiation, 1.5418 Å, 1306 independent
reflections. Final wR(F2) was 0.1092 (on 1306 reflections).
Crystal data for 7: C17H13Cl3O2, Mr = 355.62, triclinic, a =
10.121, b = 9.776, c = 9.946, V = 790.5 Å3, T = 293 K, space
group P1, Z = 2, MoKa radiation, 0.71609 Å, 2676
independent reflections. Final wR(F2) was 0.1305 (on 2676
reflections). A similar stereochemical outcome is reported
for the cyclisation of an analogous amide deriveative, see:
Parvez, M.; Lander, S. W.; DeShong, P. Acta Crystallogr.,
Sect. C 1992, 48, 568.
Hz, NH), 5.2 (2 H, m, CH=CH2), 5.8 (1 H, m, CH=CH2). 13
C
(23) Kosugi, H.; Tagami, K.; Takahashi, A.; Kanna, H.; Uda, H.
J. Chem. Soc., Perkin Trans. 1 1989, 935.
(24) Pearson, A. J.; Khan, M.; Nazrul, I.; Clardy, J. C.; He, C. H.
J. Am. Chem. Soc. 1985, 107, 2748.
NMR (75 MHz, CDCl3) d (ppm): 133.6, 117.9, 80.5, 52.9,
50, 40.8, 45.7, 44.3, 38.9, 30.4, 27.2, 20.4, 19.7. IR (cm–1,
CHCl3): 3515, 3285, 2953. m/e (CI): 291 [(M + NH4)+,
30%], 256 (100%). HRMS: C13H23O3SN, (M+H)+ calcd:
274.1477; found: 274.1477. To a solution of the sulfonamide
22 (1.6 g; 5.86 mmol) in anhydrous THF (15 mL) at –78 °C
was added n-BuLi (4.4 mL, 1.2 equiv, 1.6 M solution in
hexanes). After 30 min at –78 °C trichloroacetylchloride
(0.72 mL, 1.1 equiv) was added and the reaction mixture left
to stir at this temperature for period of two hours. On
warming up to 0 °C the reaction was quenched with
saturated ammonium chloride solution (50 mL) and
extracted with Et2O (3 × 50 mL). The organic extracts were
dried (MgSO4), concentrated in vacuo and the residue
chromatographed (‘flash’ silica; eluent: 20% EtOAc–
petroleum ether) to afford the sulfonamide 26 as a viscous
colourless oil (90% yield). 1H NMR (300 MHz, CDCl3) d
(ppm): 0.9 (3 H, s, Me), 1.05 (3 H, s, Me), 1.4–1.8 (7 H, m),
3.4 (1 H, d, J = 13.2 Hz, CH2SO), 3.95 (1 H, d, J = 13.2 Hz,
CH2SO), 4.2 (1 H, dd, J = 4.1, 7.6 Hz, CH-OH), 4.8 (2 H, m,
CH2-CH=CH2), 5.45 (2 H, m, CH=CH2), 6.0 (1 H, m,
CH=CH2). 13C NMR (75 MHz, CDCl3) d (ppm): 163.6,
131.5, 120.5, 90.0, 76.3, 55.3, 50.9, 50.6, 49.2, 44.3, 38.9,
30, 27.2, 20.5, 19.7. IR (cm–1, CHCl3): 3568, 2955, 1760,
1707. m/e (CI): 435 [(M + NH4)+, 70%], 234 (35%), 108
(100%). HRMS: C15H22O4SN35Cl3 calcd: 417.0335; found:
417.0335.
(25) Intermolecular Kharasch reactions with dienes has been
reported, see: (a) Startsev, V. V.; Zubritskii, L. M.; Sobolev,
V. G.; Petrov, A. A. Zh. Obshch. Khim. 1985, 55, 702.
(b) Shvekhgeimer, G. A.; Kobrakov, K. I.; Popandopulo, N.
G. Dokl. Akad. Nauk SSSR 1988, 302, 351. (c) Startsev, V.
V.; Zubritskii, L. M.; Petrov, A. A. Zh. Obshch. Khim. 1988,
58, 1592.
(26) See for representative examples: (a) Ghelfi, F.; Bellesia, F.;
Forti, L.; Ghirardini, G.; Grandi, R.; Libertini, E.;
Montemaggi, M. C.; Pagnoni, U. M.; Pinetti, A.; De Buyck,
L.; Parsons, A. F. Tetrahedron 1999, 55, 5839. (b) Clark,
A. J.; De Campo, F.; Deeth, R. J.; Filik, R. P.; Gatard, S.;
Hunt, N. A.; Lastecoueres, D.; Thomas, G. H.; Verlhac, J.;
Wongtap, H. J. Chem Soc., Perkin Trans. 1 2000, 671.
(c) Jones, K.; McCarthy, C. Tetrahedron Lett. 1989, 30,
2657.
(27) Trichloroacetamides were prepared from the respective
sulfonamides by acylation with trichloroacetylchloride. The
following procedures are representative:
Synthesis of sulfonamide 23 (Scheme 4).
To a solution of camphorsulfonyl chloride (13.2 g, 52.69
mmol) in dichloromethane (20 mL) was added a mixture of
triethylamine (7.32 mL, 1 equiv) and allylamine (3.9 mL, 2
equiv) in anhydrous dichloroethane (20 mL). The reaction
mixture was left at r.t. for 3 h and then poured into Et2O and
partitioned with 1 M HCl (100 mL). The organic layer was
separated, dried (MgSO4) and concentrated in vacuo to
(28) Catalyst loadings of 30 mol% are not untypical for such
reactions, especially for the cyclisation of esters to lactones,
as noted in ref.14
Synlett 2003, No. 12, 1797–1800 © Thieme Stuttgart · New York