Diastereoselective synthesis of dihydropyrans via prins cyclization of enol ethers: Total asymmetric synthesis of (+)-civet cat compound

Article abstract of DOI:10.1021/jo4015547

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) can be efficiently used for Prins cyclization of acrylyl enol ethers to 5,6-dihydro-2H-pyran-2-acetates stereo- and regioselectively in good yields. The methodology was used for the total synthesis of natu

Full text of DOI:10.1021/jo4015547

Note
pubs.acs.org/joc
Diastereoselective Synthesis of Dihydropyrans via Prins Cyclization
of Enol Ethers: Total Asymmetric Synthesis of (+)-Civet Cat
Compound
Sabera Sultana, Kiran Indukuri, Manash J. Deka, and Anil K. Saikia*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
S
* Supporting Information
ABSTRACT: Trimethylsilyl trifluoromethanesulfonate (TMSOTf) can be efficiently used for Prins cyclization of acrylyl enol
ethers to 5,6-dihydro-2H-pyran-2-acetates stereo- and regioselectively in good yields. The methodology was used for the total
synthesis of natural product (+)-civet.
ihydropyrans are important structural units found in
many biologically active natural products such as
methodology for the stereo- and regioselective synthesis of
5,6-dihydro-2H-pyran-2-acetates using the Prins enol-ether
cyclization reaction.
D
laulimalide1 and aspergillide C (Figure 1).2 This is also
In continuation of our interest in the synthesis of
dihydropyrans,9,11g we were in search of a stereo- and
regioselective methodology for the synthesis of dihydropyrans.
Initially, we investigated the reactions of enol-ether 1b, which
was prepared according to a literature procedure14b with BF3·
Et2O (entry 1) in dry dichloromethane at room temperature.
Although the reaction gave the desired 5,6-dihydropyran
product 2b in 25% yield, it also generated 4-chlorobenzalde-
hyde 3 and alcohol 415 as side products. The reaction was then
carried out with different Lewis acids and solvents, and the
results are summarized in Table 1. It was concluded from the
results in Table 1 that FeCl3, Sc(OTf)3, and Bi(OTf)3 (entries
2, 3, and 6) are not suitable reagents for this transformation
because they instead generated the aldehyde and alcohol.
However, In(OTf)3 and InCl3 (entries 4 and 5) did not provide
any products. The reaction with triflic acid (TfOH) resulted in
an intractable mixture containing minor amounts of dihy-
dropyran (see the Supporting Information). TMSOTf (entry 7)
was found to be a good reagent for the cyclization reaction,
with a 66% yield. The reaction was performed at −20 °C (entry
9) but gave only a 54% yield. The reaction was also performed
in acetonitrile (entry 10) and benzene. Although there was no
reaction in acetonitrile, an inseparable 3:2 mixture (76%) of 4-
phenyl tetrahydropyrans 5 and 5,6-dihydropyran 2b was
formed in benzene (Scheme 1).
Figure 1. Structures of natural products.
important from a synthetic point of view because of the fact
that the CC functionality of the dihydropyrans can be
modified to generate polyfunctional tetrahydropyrans by
various oxidation and reduction reactions.3 They can also be
used as synthetic intermediates for the preparation of
homoallylic alcohols.4 Apart from these synthetic applications,
substituted dihydropyrans are used as a flavoring material for
food and beverages.5 The dihydropyrans are generally
synthesized by hetero-Diels−Alder reactions,6 olefin meta-
thesis,7 base-promoted cyclizations of sulfenyl dienols,8
oxonium-ene reactions,9 [4 + 2] annulations of crotylsilanes,10
and Prins cyclization reactions.11 The Prins cyclization is an
important reaction for the synthesis of dihydro- and
tetrahydropyrans because of its diastereoselectivity.11 Generally,
Prins cyclization reactions of homoallylic/homopropargylic
alcohols and aldehydes are conducted under Lewis acidic
conditions to form dihydropyrans. The drawback of this type of
reaction is the formation of 4-hydroxy tetrahydropyrans and
corresponding ethers.12 In most cases, the reaction is not
regioselective.12 To circumvent this problem, several groups
introduced the silyl-Prins reaction.13 We now present a
The reaction was generalized with different substituents in
the homoallyl alcohol component, and the results are
summarized in Table 2. The reaction gave only one
diastereomer, 2, with 2,6-cis configurations, which was
Received: July 19, 2013
© XXXX American Chemical Society
A
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The Journal of Organic Chemistry
Note
Table 1. Optimization of the Reaction
a
entry
Lewis acid
temp.
solvents
products (% yield)
1
2
3
4
5
6
7
8
9
10
BF3·Et20
FeCl3
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
0 °C to rt
rt
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
2b (25)
3 (21)
3 (26)
3 (30)
4 (19)
4 (16)
4 (27)
1b (31)
1b (44)
1b (23)
1b (90)
1b (94)
1b (26)
Sc(OTf)3
ln(OTf)3
lnCl3
Bi(OTf)3
TMSOTf
TMSOTf
TMSOTf
TMSOTf
3 (33)
trace
4 (28)
trace
2b (66)
2b (64)
2b (54)
trace
trace
−20 °C
0 °C to rt
trace
trace
1b (35)
1b (95)
a
Yields refer to isolated yield. The compounds were characterized by IR, NMR, and mass spectrometry.
The formation of aldehyde 3 and alcohol 4 (Table 1) can be
explained by fragmentation reactions from intermediate cation
8. A generalized mechanism for these types of crossover
products is shown in Scheme 3. The tetrahydropyranyl cation 8
undergoes retro-Prins fragmentation in two different pathways,
A and B, to give aldehydes 10 and 13 and alcohols 11 and 14,
respectively, after hydrolysis of 9 and 12. Alcohol 11 and
aldehyde 13 combine under these reaction conditions to give
cross-over product 2m′, as shown in Table 1.
Scheme 1. Reaction in Benzene
The methodology was utilized for the asymmetric synthesis
of cis-6-methyltetrahydropyran-2-yl acetic acid, or civet, which
was isolated from the glandular secretions of the civet cat by
Maurer in 1979 and used as an additive by the perfumery
industry.19
confirmed by 1H and 13C NMR and NOE experiments (see the
Supporting Information). The reaction gave good yields with
both aromatic and aliphatic substituents. The reaction with an
aromatic group having a highly electron-withdrawing group
such as a nitro group on the aromatic ring gave decomposed
products (entry h). However, p-tolyl-substituted substrate 1m
gave 2m in 30% yield and cross-over product diethyl 5,6-
dihydro-2H-pyran-2,6-diacetate 2m′ in 33% yield. The reaction
is also regiospecific, and only the 5,6-dihydropyran re-
gioisomers were formed in the reactions. The olefin
regiochemistry was proved in one case by converting 2a to
The synthetic strategy was related to that used in
Nussbaumer and Frater’s synthesis of racemic 20.14a The
synthesis started with (2S)-pent-4-en-2-ol (15) as shown in
Scheme 4. (2S)-Pent-4-en-2-ol was O-alkylated with ethyl
propiolate (16) in the presence of N-methyl morpholine
(NMM) in dichloromethane to give enol ether 17 in 80% yield.
Prins cyclization of enol ether 17 and subsequent hydro-
genation with palladium on charcoal gave tetrahydropyran 19,
which was then hydrolyzed with methanolic sodium hydroxide
to give the civet cat compound in 85% yield and in 17% yield
over four steps. The specific rotation of the synthesized civet
cat compound was found to be [α]2D0 +22.4° (c 0.25, CHCl3),
which compares favorably with the literature data: lit.20a [α]D20
+22.0° (c 1.23, CHCl3), lit.20b [α]D20 +21.0° (c 0.3, CHCl3), and
the corresponding known methyl ester.16 The H and 13C
1
NMR spectra of this material were clearly different from those
reported for the methyl ester of regioisomeric 3,6-dihydropyr-
an.13f,16 This contrasts with the formation of benzyl 2-(6-
methyl-dihydropyranyl)acetate as a mixture of olefin re-
gioisomers in the indium triflate-promoted reaction of pent-4-
en-2-ol with benzyl 3-oxopropanoate.12
The proposed mechanism is shown in Scheme 2. Lewis acid
activation of the carbonyl group of the ester functionality of
enol ether 1 leads to the formation of oxocarbenium ion 7,
which after Prins cyclization forms tetrahydropyranyl cation 8.
The side-chain enolate abstracts a proton from C-3 of the
tetrahydropyranyl carbocation 8, which is acidic in nature
because of the presence of a positive charge in the α position,
via a second six-membered cyclic transition state to form the
3,4-double bond in final compound 2.17 Another possibility is
that the bulky equatorial silyl-enol ether and axial hydrogen at
C-3 of carbocation 8′ experiences a steric constraint. To release
this steric constraint, the axial hydrogen at C-3 eliminates to
give the selective elimination product 2.18 This explains the
formation of a single regioisomer.
lit.20c [α]D20 +21.9° (c 1.108, CHCl3). The H and 13C NMR
1
spectral data are in good agreement with those previously
reported for the civet cat secretion.20 The good agreement of
the specific rotation with the reported data indicates that under
these reaction conditions the product does not undergo
racemization11g,21 (Scheme 4).
In conclusion, we have developed a methodology for the
synthesis of 5,6-dihydro-2H-pyran-2-acetates from enol ethers
using the Prins cyclization reaction. The reaction is diastereo-
and regioselective and proceeds in good yields in most cases.
The utility of this methodology was demonstrated by a short
asymmetric synthesis of a natural product (+)-civet cat
secretion from (S)-pent-4-en-2-ol n in good yield.
B
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Note
Table 2. Synthesis of Dihydropyrans
a
Yields refer to isolated yield. dp, decomposed products. The compounds were characterized by IR, NMR, and mass spectrometry.
(E)-Ethyl 3-((1-(4-Chlorophenyl)but-3-en-1-yl)oxy)acrylate (1b).
Pale-yellow oil (235 mg, 84%). 1H NMR (400 MHz, CDCl3): δ
1.23 (t, J = 7.2 Hz, 3H), 2.48−2.55 (m, 1H), 2.64−2.71 (m, 1H), 4.11
(q, J = 7.2 Hz, 2H), 4.87 (t, J = 6.0 Hz, 1H), 5.06−5.10 (m, 2H), 5.19
(d, J = 12.8 Hz, 1H), 5.64−5.75 (m, 1H), 7.21 (d, J = 8.4 Hz, 2H),
7.34 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 12.8 Hz, 1H). 13C NMR (100
MHz, CDCl3): δ 14.3, 41.7, 59.7, 83.0, 98.8, 118.6, 127.6, 128.9, 132.5,
134.0, 138.1, 161.0, 167.4. IR (KBr, neat): 2983, 2935, 1710, 1634,
1487, 1368, 1132, 1043, 829, 744 cm−1. HRMS (APCI) calcd for
C15H18ClO3 (M + H)+, 281.0939; found, 281.0949.
EXPERIMENTAL SECTION
■
General Experimental Section. H and 13C NMR spectra were
recorded in CDCl3 on 600, 400, and (150, 100, 75) MHz NMR
spectrometer, respectively, using TMS as an internal standard. Chiral
(S)-pent-4-ene-2-ol (15) was purchased from a chemical supplier.
Compounds 1a and 1k are known compounds that were prepared
according to a literature procedure.14c Their IR, NMR, and HRMS
data agreed well with the reported data. The same procedure14c was
used to prepare compounds 1b−1j, 1l, and 1m. Compounds 19 and
20 are also known, and their preparations were carried out according
to literature procedures. The IR, NMR, and HRMS data for these
compounds agree well with the respective literature data.
1
(E)-Ethyl 3-((1-(2-Chlorophenyl)but-3-en-1-yl)oxy)acrylate (1c).
Pale-yellow oil (232 mg, 83%). 1H NMR (400 MHz, CDCl3): δ
1.15 (t, J = 7.2 Hz, 3H), 2.53 (dd, J = 6.8 and 5.6 Hz, 2H), 4.06 (q, J =
C
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The Journal of Organic Chemistry
Note
Scheme 2. Mechanism of the Reaction
Scheme 3. Mechanism for the Formation of Alcohols 11 and 14 and Aldehydes 10 and 13
Scheme 4. Short Synthesis of (+)-Civet
7.2 Hz, 2H), 5.02−5.06 (m, 2H), 5.09 (d, J = 12.4 Hz, 1H), 5.30 (t, J =
6.0 Hz, 1H), 5.68−5.79 (m, 1H), 7.14−7.32 (m, 4H), 7.43 (d, J = 12.4
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 14.3, 40.2, 59.7, 79.7, 98.7,
118.5, 127.2, 127.4, 129.3, 129.4, 129.6, 132.7, 137.2, 161.1, 167.5. IR
(KBr, neat): 2983, 2939, 1710, 1633, 1470, 1320, 1132, 1043, 830, 755
cm−1. HRMS (APCI) calcd for C15H18ClO3 (M + H)+, 281.0939;
found, 281.0949.
4.15 (m, 2H), 4.96 (dd, J = 7.2 and 5.6 Hz, 1H), 5.05−5.10 (m, 2H),
5.19 (d, J = 12.8 Hz, 1H), 5.63−5.75 (m, 1H), 7.35 (d, J = 8.4 Hz,
2H), 7.51 (d, J = 12.8 Hz, 1H), 8.04 (d, J = 8.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3): δ 14.3, 41.7, 59.8, 82.9, 98.9, 118.8, 122.8, 124.8,
129.1, 130.3, 131.4, 132.4, 141.9, 161.0, 167.5. IR (KBr, neat): 2982,
2937, 1707, 1634, 1471, 1194, 1043, 831, 742 cm−1. HRMS (APCI)
calcd for C15H18BrO3 (M + H)+, 325.0434; found, 325.0442.
(E)-Methyl 4-(1-((3-Ethoxy-3-oxoprop-1-en-1-yl)oxy)but-3-en-1-
yl)benzoate (1f). Pale-yellow oil (273 mg, 90%). 1H NMR (400
MHz, CDCl3): δ 1.22 (t, J = 7.2 Hz, 3H), 2.51−2.59 (m, 1H), 2.66−
2.73 (m, 1H), 3.91 (s, 3H), 4.06−4.15 (m, 2H), 4.96 (dd, J = 7.2 and
5.6 Hz, 1H), 5.05−5.10 (m, 2H), 5.19 (d, J = 12.8 Hz, 1H), 5.63−5.75
(m, 1H), 7.35 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 12.8 Hz, 1H), 8.04 (d, J
= 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 14.4, 41.8, 52.3, 59.9,
83.2, 99.1, 118.9, 126.3, 130.1, 130.2, 132.5, 144.7, 161.1, 166.7, 167.6.
IR (KBr, neat): 2985, 1720, 1635, 1445, 1282, 1129, 1044, 829, 770
cm−1. HRMS (APCI) calcd for C17H21O5 (M + H)+, 305.1384; found,
305.1397.
(E)-Ethyl 3-((1-(4-Bromophenyl)but-3-en-1-yl)oxy)acrylate (1d).
1
Colorless oil (288 mg, 89%). H NMR (400 MHz, CDCl3): δ 1.23
(t, J = 7.2 Hz, 3H), 2.48−2.55 (m, 1H), 2.63−2.70 (m, 1H), 4.01−
4.16 (m, 2H), 4.85 (t, J = 7.2 Hz, 1H), 5.06−5.11 (m, 2H), 5.18 (d, J =
12.8 Hz, 1H), 5.64−5.75 (m, 1H), 7.14 (d, J = 8.4 Hz, 2H), 7.47 (d, J
= 12.8 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz,
CDCl3): δ 14.3, 41.7, 59.8, 83.0, 98.9, 118.7, 122.2, 127.9, 131.9, 132.5,
138.6, 161.0, 167.5. IR (KBr, neat): 2983, 2940, 1712, 1632, 1480,
1132, 1055, 828, 743 cm−1. HRMS (APCI) calcd for C15H18BrO3 (M
+ H)+, 325.0434; found, 325.0442.
(E)-Ethyl 3-((1-(3-Bromophenyl)but-3-en-1-yl)oxy)acrylate (1e).
(E)-Ethyl 3-((1-(Naphthalen-2-yl)but-3-en-1-yl)oxy)acrylate (1g).
Colorless oil (230 mg, 78%). 1H NMR (400 MHz, CDCl3): δ 1.18 (t, J
= 7.2 Hz, 3H), 2.57−2.65 (m, 1H), 2.73−2.79 (m, 1H), 4.01−4.13 (m,
1
Colorless oil (278 mg, 86%). H NMR (400 MHz, CDCl3): δ 1.22
(t, J = 7.2 Hz, 3H), 2.51−2.59 (m, 1H), 2.66−2.73 (m, 1H), 4.06−
D
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Note
2H), 5.01−5.12 (m, 3H), 5.24 (d, J = 12.4 Hz, 1H), 5.68−5.79 (m,
1H), 7.37 (dd, J = 8.8 and 1.6 Hz, 1H), 7.46−7.51 (m, 2H), 7.53 (d, J
= 12.4 Hz, 1H), 7.70 (s, 1H), 7.80−7.85 (m, 3H). 13C NMR (100
MHz, CDCl3): δ 14.4, 41.8, 59.8, 84.1, 98.8, 118.5, 123.8, 125.7, 126.4,
126.5, 127.9, 128.1, 128.9, 133.0, 133.2, 133.3, 137.0, 161.4, 167.8. IR
(KBr, neat): 2981, 2934, 1706, 1633, 1324, 1130, 1045, 824, 749 cm−1.
HRMS (APCI) calcd for C19H21O3 (M + H)+, 297.1485; found,
297.1500.
purified by short column chromatography over silica gel (EtOAc/
hexane 1:9) to give 2a (147 mg, 60%) as a colorless oil. 1H NMR (400
MHz, CDCl3): δ 1.26 (t, J = 7.2 Hz, 3H), 2.25−2.29 (m, 2H), 2.55
(dd, J = 15.2 and 6.4 Hz, 1H), 2.68 (dd, J = 15.2 and 7.6 Hz, 1H), 4.16
(dq, J = 7.2 and 2.4 Hz, 2H), 4.64 (dd, J = 8.8 and 5.2 Hz, 1H), 4.73−
4.78 (m, 1H), 5.76 (ddd, J = 9.6, 3.6, and 1.6 Hz, 1H), 5.76 (ddd, J =
9.6, 4.8, and 2.4 Hz, 1H), 7.23−7.29 (m, 2H), 7.31−7.42 (m, 3H). 13C
NMR (100 MHz, CDCl3): δ 14.4, 32.9, 40.9, 60.7, 72.5, 75.7, 125.8,
127.5, 128.5, 128.7, 129.0, 142.6, 171.3. IR (KBr, neat): 2921, 2847,
1730, 1602, 1453, 1382, 1285, 1172, 1070, 1026, 752, 696 cm−1.
HRMS (APCI) calcd for C15H19O3 (M + H)+, 247.1329; found,
247.1332. Compound 2a was transesterified using trimethylsilyl
chloride in methanol, as per a literature procedure,22 to the
corresponding methyl ester, methyl 2-((2S,6S)-6-phenyl-5,6-dihydro-
2H-pyran-2-yl)acetate 2a′ as a colorless oil (150 mg, 65%). The NMR,
IR, and HRMS data agreed well with the reported data (see the
Supporting Information for spectra).16
(E)-Ethyl 3-((1-(4-Nitrophenyl)but-3-en-1-yl)oxy)acrylate (1h).
Colorless solid, mp 109−110 °C (238 mg, 82%). 1H NMR (400
MHz, CDCl3): δ 1.25 (t, J = 7.2 Hz, 3H), 2.56−2.61 (m, 1H), 2.67−
2.72 (m, 1H), 4.07−4.14 (m, 2H), 5.04 (t, J = 6.8 Hz, 1H), 5.05−5.11
(m, 2H), 5.20 (d, J = 12.8 Hz, 1H), 5.68−5.75 (m, 1H), 7.46 (d, J =
8.4 Hz, 2H), 7.59 (d, J = 12.8 Hz, 1H), 8.24 (d, J = 8.4 Hz, 2H). 13C
NMR (100 MHz, CDCl3): δ 14.3, 41.6, 60.0, 82.4, 99.4, 119.4, 124.0,
127.1, 131.9, 146.8, 147.8, 166.1, 167.3. IR (KBr, neat): 2983, 2929,
1711, 1615, 1524, 1341, 1189, 1132, 1042, 848, 745 cm−1. HRMS
(APCI) calcd for C15H17NO5 (M + H)+, 292.1179; found, 292.1178.
(E)-Ethyl 3-((1-Phenylpent-4-en-2-yl)oxy)acrylate (1i). Colorless
oil (236 mg, 91%). 1H NMR (400 MHz, CDCl3): δ 1.25 (t, J = 7.2 Hz,
3H), 2.37 (t, J = 7.2 Hz, 2H), 2.86−2.95 (m, 2H), 4.10−4.19 (m, 3H),
5.09−5.17 (m, 2H), 5.24 (d, J = 12.4 Hz, 1H), 5.75−5.82 (m, 1H),
7.17 (d, J = 6.8 Hz, 2H), 7.23−7.31 (m, 3H), 7.41 (d, J = 12.4 Hz,
1H). 13C NMR (100 MHz, CDCl3): δ 14.5, 38.2, 40.3, 59.8, 83.9, 97.6,
118.8, 126.9, 128.7, 129.6, 133.1, 137.1, 162.2, 168.1. IR (KBr, neat):
2982, 2933, 1703, 1641, 1322, 1132, 1025, 832, 701 cm−1. HRMS
(APCI) calcd for C16H21O3 (M + H)+, 261.1485; found, 261.1489.
(E)-Ethyl 3-((6-Methylhept-1-en-4-yl)oxy)acrylate (1j). Pale-yellow
Ethyl-2-(6-(4-chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)acetate
1
(2b). Colorless oil (184 mg, 66%). H NMR (400 MHz, CDCl3): δ
1.26 (t, J = 7.2 Hz, 3H), 2.20−2.25 (m, 2H), 2.54 (dd, J = 15.2 and 7.5
Hz, 1H), 2.67 (dd, J = 15.2 and 7.5 Hz, 1H), 4.14−4.20 (m, 2H), 4.61
(dd, J = 8.8 and 5.2 Hz, 1H), 4.72−4.80 (m, 1H), 5.74−5.79 (m, 1H),
5.91−5.96 (m, 1H), 7.22−7.35 (m, 4H). 13C NMR (100 MHz,
CDCl3): δ 14.4, 32.9, 40.9, 60.7, 72.5, 74.9, 125.6, 127.2, 128.6, 129.1,
133.1, 141.2, 171.2. IR (KBr, neat): 2981, 2925, 1735, 1655, 1492,
1393, 1166, 1163, 1085, 1030, 823 cm−1. HRMS (APCI) calcd for
C15H17ClO3 (M + H)+, 281.0939; found, 281.0949.
Ethyl-2-(6-(2-chlorophenyl)-5,6-dihydro-2H-pyran-2-yl)acetate
1
1
(2c). Colorless oil (187 mg, 67%). H NMR (400 MHz, CDCl3): δ
oil (164 mg, 73%). H NMR (400 MHz, CDCl3): δ 0.87 (d, J = 6.4
1.26 (t, J = 7.2 Hz, 3H), 2.40−2.50 (m, 2H), 2.56 (dd, J = 15.2 and 6.4
Hz, 1H), 2.68 (dd, J = 15.2 and 7.6 Hz, 1H), 4.11−4.22 (m, 2H),
4.74−4.84 (m, 1H), 4.98 (dd, J = 10.4 and 3.2 Hz, 1H), 5.75−5.79 (m,
1H), 5.92−5.98 (m, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.27 (d, J = 7.6 Hz,
1H), 7.30 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 7.6 Hz, 1H). 13C NMR (100
MHz, CDCl3): δ 14.4, 31.4, 41.0, 60.7, 72.6, 72.7, 125.9, 127.2, 127.3,
128.5, 128.8, 129.2, 131.6, 140.4, 171.2. IR (KBr, neat): 2979, 2925,
1735, 1585, 1473, 1380, 1172, 1079, 1037, 756 cm−1. HRMS (ESI)
calcd for C15H17ClNaO3 (M + Na)+, 303.0758; found, 303.0756.
Ethyl-2-(6-(4-bromoophenyl)-5,6-dihydro-2H-pyran-2-yl)acetate
Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H), 1.28−1.34
(m, 1H), 1.51−1.58 (m, 1H), 1.62−1.72 (m, 1H), 2.31 (t, J = 5.6 Hz,
2H), 3.95−4.01 (m, 1H), 4.12 (q, J = 7.2 Hz, 2H), 5.05−5.11 (m,
2H), 5.21 (d, J = 12.4 Hz, 1H), 5.66−5.77 (m, 1H), 7.48 (d, J = 12.4
Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 14.0, 21.7, 22.7, 24.1, 38.8,
42.6, 59.1, 81.1, 96.8, 118.0, 132.8, 162.0, 167.5. IR (KBr, neat): 2955,
1711, 1633, 1463, 1376, 1207, 1130, 1043, 832, 742 cm−1. HRMS
(APCI) calcd for C13H23O3 (M + H)+, 227.1642; found, 227.1658.
(E)-Ethyl 3-((1-Cyclohexylbut-3-en-1-yl)oxy)acrylate (1l). Pale-
1
yellow oil (179 mg, 71%). H NMR (400 MHz, CDCl3): δ 0.90−
1
(2d). Colorless oil (223 mg, 69%). H NMR (400 MHz, CDCl3): δ
1.07 (m, 3H), 1.10−1.27 (m, 6H), 1.49−1.69 (m, 5H), 1.76−2.10 (m,
1H), 2.22−2.28 (m, 1H), 4.08 (q, J = 7.2 Hz, 2H), 4.14−4.21 (m,
1H), 5.00−5.07 (m, 2H), 5.15 (d, J = 12.8 Hz, 1H), 5.63−5.81 (m,
1H), 7.41 (d, J = 12.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 14.4,
26.0, 26.1, 26.4, 28.1, 28.9, 35.9, 41.4, 59.6, 88.5, 96.7, 118.1, 133.7,
163.5, 169.4. IR (KBr, neat): 2928, 2856, 1711, 1632, 1450, 1244,
1132, 1042, 832, 743 cm−1. HRMS (APCI) calcd for C15H25O3 (M +
H)+, 253.1798; found, 253.1798.
1.27 (t, J = 7.2 Hz, 3H), 2.20−2.27 (m, 2H), 2.54 (dd, J = 15.2 and 6.4
Hz, 1H), 2.67 (dd, J = 15.2 and 7.6 Hz, 1H), 4.11−4.21 (m, 2H), 4.60
(dd, J = 8.4 and 4.8 Hz, 1H), 4.72−4.79 (m, 1H), 5.74−5.79 (m, 1H),
5.90−5.96 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H).
13C NMR (100 MHz, CDCl3): δ 14.4, 32.9, 40.9, 60.7, 72.5, 75.0,
121.3, 125.6, 127.6, 129.1, 131.5, 141.7, 171.2. IR (KBr, neat): 2923,
2850, 1733, 1647, 1483, 1382, 1169, 1077, 1023, 678 cm−1. HRMS
(ESI) calcd for C15H17BrNaO3 (M + Na)+, 347.0253; found, 347.0251
(major) and 349.0207 (minor).
(E)-Ethyl 3-((1-(p-Tolyl)but-3-en-1-yl)oxy)acrylate (1m). Pale-
1
yellow oil (241 mg, 93%). H NMR (400 MHz, CDCl3): δ 1.18 (t,
J = 7.2 Hz, 3H), 2.30 (s, 3H), 2.46−2.54 (m, 1H), 2.63−2.71 (m, 1H),
4.02−4.10 (m, 2H), 4.84 (dd, J = 7.2 and 6.4 Hz, 1H), 5.04−5.10 (m,
2H), 5.21 (d, J = 12.8 Hz, 1H), 5.65−5.78 (m, 1H), 7.00−7.18 (m,
4H), 7.50 (d, J = 12.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 14.3,
21.0, 41.7, 59.5, 83.3, 98.3, 118.0, 126.1, 129.3, 133.1, 136.5, 137.9,
161.3, 167.5. IR (KBr, neat): 2983, 2932, 1709, 1635, 1452, 1318,
1132, 819, 750 cm−1. HRMS (APCI) calcd for C16H21O3 (M + H)+,
261.1485; found, 261.1480.
Synthesis of Ethyl-2-(6-phenyl-5,6-dihydro-2H-pyran-2-yl)acetate
(2a). To a solution of (E)-ethyl-3-((1-phenylbut-3-en-1-yl)oxy)-
acrylate (246 mg, 1.00 mmol) in dry dichloromethane (2 mL) at 0
°C was added trimethylsilyl trifluoromethane sulfonate (0.18 mL, 1.00
mmol) under a N2 atmosphere. The temperature was slowly brought
to room temperature. The reaction mixture was stirred at room
temperature for 1 h. The progress of the reaction was monitored by
TLC with ethyl acetate and hexane (EtOAc/hexane 1:9) as eluents.
After the completion of the reaction, the solvent was removed on a
rotary evaporator and quenched with a saturated solution of NaHCO3
(3 mL). The product was extracted with ethyl acetate (2 × 15 mL)
and then washed with brine solution (3 mL). The organic layer was
dried (Na2SO4) and evaporated to give the crude product, which was
Ethyl-2-(6-(3-bromoophenyl)-5,6-dihydro-2H-pyran-2-yl)acetate
1
(2e). Colorless oil (233 mg, 72%). H NMR (400 MHz, CDCl3): δ
1.28 (t, J = 7.2 Hz, 3H), 2.21−2.27 (m, 2H), 2.54 (dd, J = 14.8 and 6.0
Hz, 1H), 2.67 (dd, J = 14.8 and 7.6 Hz, 1H), 4.12−4.22 (m, 2H), 4.61
(dd, J = 9.2 and 5.2 Hz, 1H), 4.71−4.79 (m, 1H), 5.74−5.79 (m, 1H),
5.90−5.96 (m, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.26 (d, J = 7.6 Hz, 1H),
7.38 (d, J = 7.6 Hz, 1H), 7.53 (s, 1H). 13C NMR (100 MHz, CDCl3):
δ 14.4, 32.7, 40.8, 60.7, 72.4, 74.7, 122.5, 124.3, 125.4, 128.8, 128.9,
129.9, 130.4, 144.9, 171.1. IR (KBr, neat): 2923, 2850, 1733, 1569,
1381, 1170, 1078, 1029, 781, 695 cm−1. HRMS (ESI) calcd for
C15H17BrNaO3 (M + Na)+, 347.0253; found, 347.0251 (major) and
349.0207 (minor).
Methyl-4-(6-(2-ethoxy-2-oxoethyl)-3,6-dihydro-2H-pyran-2-yl)-
1
benzoate (2f). Colorless liquid (194 mg, 64%). H NMR (400 MHz,
CDCl3): δ 1.28 (t, J = 7.2 Hz, 3H), 2.21−2.30 (m, 2H), 2.56 (dd, J =
15.2 and 6.4 Hz, 1H), 2.69 (dd, J = 15.2 and 7.6 Hz, 1H), 3.91 (s, 3H),
4.11−4.23 (m, 2H), 4.70 (dd, J = 10.0 and 4.0 Hz, 1H), 4.74−4.80 (m,
1H), 5.75−5.80 (m, 1H), 5.93−5.98 (m, 1H), 7.43 (d, J = 8.0 Hz,
2H), 7.99 (d, J = 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ 14.4,
32.8, 40.8, 52.2, 60.7, 72.4, 75.1, 125.5, 125.6, 129.0, 129.1, 129.7,
147.7, 167.1, 171.2. IR (KBr, neat): 2945, 2850, 1727, 1617, 1438,
E
dx.doi.org/10.1021/jo4015547 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
1382, 1174, 1105, 1025, 764, 702 cm−1. HRMS (APCI) calcd for
C17H20O5 (M + H)+, 305.1384; found, 305.1394.
(m, 4H), 4.02−4.10 (m, 1H), 4.15 (q, J = 7.2 Hz, 4H), 4.60−4.64 (m,
1H), 5.64−5.69 (m, 1H), 5.58−5.88 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 14.4 (2C), 30.5, 40.7, 41.2, 60.8 (2C), 70.8, 72.0, 125.3,
128.8, 171.5, 171.7. IR (KBr, neat): 2980, 2924, 1733, 1579, 1378,
1286, 1166, 1081, 1031, 810, 680 cm−1. HRMS (ESI) calcd for
C13H20NaO5 (M + Na)+, 279.1203; found, 279.1210.
Ethyl 2-(6-(naphthalen-1-yl)-5,6-dihydro-2H-pyran-2-yl)acetate
1
(2g). Colorless oil (183 mg, 62%). H NMR (400 MHz, CDCl3): δ
1.27 (t, J = 7.2 Hz, 3H), 2.31−2.37 (m, 2H), 2.58 (dd, J = 14.8 and 6.4
Hz, 1H), 2.73 (dd, J = 14.8 and 7.6 Hz, 1H), 4.12−4.21 (m, 2H),
4.77−4.90 (m, 2H), 5.78−5.82 (m, 1H), 5.94−6.0 (m, 1H), 7.41−7.64
(m, 3H), 7.79−7.98 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 14.5,
32.9, 41.0, 60.7, 72.6, 75.8, 124.3, 124.4, 125.8 (2C), 126.2, 127.8,
128.2 (2C), 129.1, 133.0, 133.5, 140.1, 171.3. IR (KBr, neat): 2945,
2850, 1727, 1617, 1438, 1382, 1174, 1105, 1025, 764, 702 cm−1.
HRMS (ESI) calcd for C19H20NaO3 (M + Na)+, 319.1305; found,
319.1317.
Ethyl-2-(6-benzyl-5,6-dihydro-2H-pyran-2-yl)acetate (2i). Color-
less oil (166 mg, 64%). 1H NMR (600 MHz, CDCl3): δ 1.24 (t, J = 7.2
Hz, 3H), 1.86−1.92 (m, 1H), 2.00−2.07 (m, 1H), 2.44 (dd, J = 15.0
and 6.0 Hz, 1H), 2.55 (dd, J = 15.0 and 8.4 Hz, 1H), 2.68 (dd, J = 14.0
and 6.0 Hz, 1H), 2.93 (dd, J = 14.0 and 6.8 Hz, 1H), 3.77−3.80 (m,
1H), 4.07−4.17 (m, 2H), 4.50−4.55 (m, 1H), 5.62−5.66 (m, 1H),
5.78−5.83 (m, 1H), 7.17−7.29 (m, 5H). 13C NMR (100 MHz,
CDCl3): δ 14.4, 30.7, 41.0, 42.4, 60.6, 72.0, 75.0, 125.7, 126.3, 128.3,
128.9, 129.7, 138.7, 171.3. IR (KBr, neat): 2923, 2848, 1734, 1596,
1376, 1170, 1085, 1033, 741, 696 cm−1. HRMS (APCI) calcd for
C16H20O3 (M + H)+, 261.1485; found, 261.1489.
Ethyl 2-(6-(4-Chlorophenyl)-4-phenyltetrahydro-2H-pyran-2-yl)-
acetate (5) and Ethyl-2-(6-(4-chlorophenyl)-5,6-dihydro-2H-pyran-
1
2-yl)acetate (2b) (5/2b 1:1). Colorless oil (250 mg, 76%). H NMR
(400 MHz, CDCl3): δ 1.20−1.30 (m, 6H), 1.50−1.68 (m, 2H), 1.96−
2.15 (m, 2H), 2.20−2.24 (m, 2H), 2.54 (dd, J = 15.2 and 7.5 Hz, 2H),
2.60−2.75 (m, 2H), 2.98−3.04 (m, 1H), 4.10−4.21 (m, 5H), 4.52−
4.55 (m, 1H), 4.58−4.62 (m, 1H), 4.72−4.78 (m, 1H), 5.75−5.78 (m,
1H), 5.91−5.95 (m, 1H), 7.19−7.35 (m, 10H), 7.43−7.46 (m, 3H).
(S,E)-Ethyl 3-(Pent-4-en-2-yloxy)acrylate (17).14c Colorless oil
1
(147 mg, 80%). H NMR (400 MHz, CDCl3): δ 1.15 (d, J = 6.0
Hz, 3H), 1.18 (t, J = 7.2 Hz, 3H), 2.18−2.24 (m, 1H), 2.28−2.36 (m,
1H), 3.98−4.10 (m, 3H), 5.00−5.10 (m, 2H), 5.15 (d, J = 12.4 Hz,
1H), 5.62−5.71 (m, 1H), 7.44 (d, J = 12.4 Hz, 1H). 13C NMR (100
MHz, CDCl3): δ 14.1, 19.2, 40.2, 59.2, 78.4, 97.1, 117.9, 132.9, 161.4,
167.5. IR (KBr, neat): 2982, 2934, 1709, 1634, 1454, 1378, 1130,
1050, 832, 740 cm−1. HRMS (APCI) calcd for C10H16O3 (M + H)+,
185.1172; found, 185.1179. [α]2D0 −8.2 (c 1.00, CH2Cl2).
Ethyl 2-(2R,6S)-6-Methyl-5,6-dihydro-2H-pyran-2-yl)acetate (18).
Prepared as per the procedure mentioned for the synthesis of
Ethyl 2-(6-Isobutyl-5,6-dihydro-2H-pyran-2-yl)acetate (2j). Color-
1
1
compound 2a. Colorless oil (161 mg, 88%). H NMR (400 MHz,
less oil (183 mg, 81%). H NMR (400 MHz, CDCl3): δ 0.84 (d, J =
CDCl3): δ 1.19 (d, J = 6.0 Hz, 3H), 1.24 (t, J = 7.2 Hz, 3H), 1.90−
1.95 (m, 2H), 2.40 (dd, J = 15.2 and 6.4 Hz, 1H), 2.55 (dd, J = 15.2
and 7.6 Hz, 1H), 3.64−3.73 (m, 1H), 4.13 (q, J = 7.2 Hz, 2H), 4.50−
4.56 (m, 1H), 5.60−5.65 (m, 1H), 5.77−5.83 (m, 1H). 13C NMR
(100 MHz, CDCl3): δ 14.4, 21.7, 32.8, 40.9, 60.7, 70.4, 71.8, 125.9,
128.9, 171.4. IR (KBr, neat): 2984, 1721, 1621, 1462, 1372, 1249,
1178, 1097, 1027, 858, 748 cm−1. HRMS (APCI) calcd for C10H16O3
(M + H)+, 185.1172; found, 185.1181. [α]D20 +3.7 (c 0.70, CH2Cl2).
Ethyl 2-((2S,6S)-6-Methyltetrahydro-2H-pyran-2-yl)acetate
6.4 Hz, 3H), 0.85 (d, J = 6.4 Hz, 3H), 1.21 (t, J = 7.2 Hz, 3H), 1.42−
1.48 (m, 1H), 1.72−1.80 (m, 1H), 1.86−1.94 (m, 2H), 1.95−2.00 (m,
1H), 2.39 (dd, J = 15.2 and 6.0 Hz, 1H), 2.50 (dd, J = 15.2 and 8.0 Hz,
1H), 3.55−3.60 (m, 1H), 4.11 (q, J = 7.2 Hz, 2H), 4.47−4.52 (m,
1H), 5.58−5.62 (m, 1H), 5.77−5.81 (m, 1H). 13C NMR (100 MHz,
CDCl3): δ 14.3, 22.5, 23.2, 24.6, 31.5, 40.9, 45.0, 60.5, 71.9, 72.5,
126.0, 129.0, 171.3. IR (KBr, neat): 2955, 2917, 1738, 1650, 1465,
1375, 1171, 1084, 1035, 685 cm−1. HRMS (APCI) calcd for C13H22O3
(M + H)+, 227.1642; found, 227.1633.
(19).12 Colorless oil (184 mg, 99%) (reported23 86 mg, 92%). H
1
Ethyl 2-(6-Hexyl-5,6-dihydro-2H-pyran-2-yl)acetate (2k). Color-
NMR (400 MHz, CDCl3): δ 1.09 (d, J = 6.4 Hz, 3H), 1.11−1.17 (m,
1H), 1.24 (t, J = 7.2 Hz, 3H), 1.40−1.65 (m, 4H), 1.72−1.79 (m, 1H),
2.32 (dd, J = 15.2 and 5.6 Hz, 1H), 2.49 (dd, J = 15.2 and 7.6 Hz, 1H),
3.37−3.44 (m, 1H), 3.68−3.75 (m, 1H), 4.09 (q, J = 7.2 Hz, 2H). 13C
NMR (100 MHz, CDCl3): δ 7.4, 17.0, 17.9, 25.4, 27.4, 35.2, 53.8, 67.6,
67.8, 165.0. IR (KBr, neat): 2923, 1730, 1636, 1457, 1371, 1257, 1091,
802 cm−1. HRMS (APCI) calcd for C10H18O3 (M + H)+, 187.1329;
found, 187.1329. [α]D20 +17.0 (c 0.50, CHCl3), lit.23 [α]D20 +16.43 (c
0.30, CHCl3).
1
less oil (200 mg, 79%). H NMR (400 MHz, CDCl3): δ 0.84 (d, J =
6.4 Hz, 3H), 1.20−1.30 (m, 9H), 1.34−1.42 (m, 2H), 1.48−1.53 (m,
2H), 1.88−1.94 (m, 2H), 2.39 (dd, J = 15.2 and 6.4 Hz, 1H), 2.52 (dd,
J = 15.2 and 7.6 Hz, 1H), 3.37−3.52 (m, 1H), 4.12 (q, J = 7.2 Hz, 2H),
4.45−4.52 (m, 1H), 5.58−5.64 (m, 1H), 5.77−5.82 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 14.1, 14.3, 22.6, 25.4, 29.3, 31.1, 31.9,
36.0, 40.8, 60.5, 71.8, 74.2, 125.8, 128.9, 171.3. IR (KBr, neat): 2956,
2928, 1738, 1653, 1466, 1395, 1164, 1081, 1031, 685 cm−1. HRMS
(APCI) calcd for C15H26O3 (M + H)+, 255.1955; found, 255.1943.
Ethyl 2-(6-Cyclohexyl-5,6-dihydro-2H-pyran-2-yl)acetate (2l).
Colorless oil (166 mg, 66%). 1H NMR (400 MHz, CDCl3): δ
0.85−0.98 (m, 2H), 1.08−1.20 (m, 2H), 1.23 (t, J = 7.2 Hz, 3H),
1.28−1.38 (m, 2H), 1.58−1.70 (m, 4H), 1.91−2.98 (m, 3H), 2.39 (dd,
J = 14.8 and 6.0 Hz, 1H), 2.50 (dd, J = 14.8 and 8.0 Hz, 1H), 3.18−
3.24 (m, 1H), 4.11 (q, J = 7.2 Hz, 2H), 4.42−4.50 (m, 1H), 5.58−5.63
(m, 1H), 5.78−5.84 (m, 1H). 13C NMR (150 MHz, CDCl3): δ 14.5,
26.1, 26.3, 26.8, 28.5, 28.6, 29.3, 41.1, 43.0, 60.6, 72.2, 78.6, 126.2,
129.1, 171.5. IR (KBr, neat): 2925, 2852, 1731, 1447, 1287, 1174,
1080, 1033, 853, 682 cm−1. HRMS (APCI) calcd for C15H24O3 (M +
H)+, 253.1797; found, 253.1795.
2-((2S,6S)-6-Methyltetrahydro-2H-pyran-2-yl)acetic Acid,
(+)-Civet (20).14a Colorless gum (134 mg, 85%) (reported20c 164
1
mg, 80%). H NMR (400 MHz, CDCl3): δ 1.15 (d, J = 6.0 Hz, 3H),
1.17−1.28 (m, 1H), 1.45−1.63 (m, 4H), 1.77−1.84 (m, 1H), 2.45 (dd,
J = 15.6 and 5.2 Hz, 1H), 2.55 (dd, J = 15.6 and 7.6 Hz, 1H), 3.46−
3.54 (m, 1H), 3.70−3.78 (m, 1H). 13C NMR (150 MHz, CDCl3): δ
22.2, 23.3, 31.0, 33.0, 41.4, 74.2, 74.8, 174.5. IR (KBr, neat): 2929,
2855, 1717, 1449, 1206, 1076, 1097, 860, 799 cm−1. HRMS (APCI)
calcd for C8H14O3 (M + H)+, 159.1016; found, 159.1016. [α]2D0 +22.4
(c 0.25, CHCl3), lit.20a [α]D20 +22.0° (c 1.23, CHCl3), lit.20b [α]2D0
+21.0° (c 0.3, CHCl3), and lit.20c [α]D20 +21.9° (c 1.108, CHCl3).
Ethyl 2-(6-(p-Tolyl)-5,6-dihydro-2H-pyran-2-yl)acetate (2m). Col-
orless oil (78 mg, 30%). H NMR (600 MHz, CDCl3): δ 1.27 (t, J =
1
ASSOCIATED CONTENT
■
7.2 Hz, 3H), 2.24−2.32 (m, 2H), 2.33 (s, 3H), 2.53 (dd, J = 15.6 and
6.6 Hz, 1H), 2.68 (dd, J = 15.6 and 7.2 Hz, 1H), 4.14−4.19 (m, 2H),
4.61 (dd, J = 10.0 and 3.6 Hz, 1H), 4.70−4.78 (m, 1H), 5.75−5.78 (m,
1H), 5.92−5.96 (m, 1H), 7.14 (d, J = 7.8 Hz, 2H), 7.25 (d, J = 7.8 Hz,
2H). 13C NMR (100 MHz, CDCl3): δ 14.4, 21.3, 32.9, 40.9, 60.7, 72.5,
75.6, 125.8, 125.9, 129.0, 129.1, 137.2, 139.7, 171.3. IR (KBr, neat):
2924, 2857, 1733, 1591, 1455, 1280, 1172, 1074, 1030, 810, 678 cm−1.
HRMS (ESI) calcd for C16H20NaO3 (M + Na)+, 283.1305; found,
283.1301.
S
* Supporting Information
1H and 13C NMR and HRMS spectra of all compounds, and
NOE spectrum of 2j. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Fax: +91-361-2690762. E-mail: asaikia@iitg.ernet.in.
Notes
Diethyl 2,2′-(3,6-Dihydro-2H-pyran-2,6-diyl)diacetate (2m′). Col-
1
orless oil (84 mg, 33%). H NMR (400 MHz, CDCl3): δ 1.26 (t, J =
7.2 Hz, 3H), 1.27 (t, J = 7.2 Hz, 3H), 2.02−2.08 (m, 2H), 2.45−2.63
The authors declare no competing financial interest.
F
dx.doi.org/10.1021/jo4015547 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(17) Jones, C. R.; Baruah, P. K.; Thompson, A. L.; Scheiner, S. J. Am.
Chem. Soc. 2012, 134, 12064−12071.
ACKNOWLEDGMENTS
■
We are grateful to the Council of Scientific and Industrial
Research (CSIR), New Delhi, for financial support (grant no.
01(2332)/09/EMR-II). We are also thankful to Ashim J.
Thakur of Tezpur University for providing the NOE spectrum.
(18) Jurberg, I. D.; Odabachian, Y.; Gagosz, F. J. Am. Chem. Soc.
2010, 132, 3543−3552.
(19) Maurer, A.; Grieder, A.; Thommen, W. Helv. Chim. Acta 1979,
62, 44−47.
(20) (a) Dixon, D. J.; Ley, S. V.; Tate, E. W. J. Chem. Soc., Perkin
Trans. 1 2000, 2385−2394. (b) O’Brien, M.; Cahill, S.; Evans, L. A.
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