Isothiourea-catalyzed asymmetric O- to C-carboxyl transfer of furanyl carbonates

Article abstract of DOI:10.1055/s-0030-1260602

The ability of a chiral isothiourea to promote the regio- and enantioselective O- to C-carboxyl transfer of a series of 3-alkyl-5-aryl- and 5-methyl-3-phenylfuranyl carbonates is examined, generating preferentially the -regioisomers (α/γ up to 83:17) with high asymmetric induction (up to 83% ee). Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1260602

PAPER
1865
Isothiourea-Catalyzed Asymmetric O- to C-Carboxyl Transfer of Furanyl
Carbonates
Asymmetric
O-
to
a
C-Carbox
r
yl Trans
o
fer of Furany
l
l
Carbo
i
nates ne Joannesse, Louis C. Morrill, Craig D. Campbell, Alexandra M. Z. Slawin, Andrew D. Smith*
EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, KY16 9ST, UK
Fax +44(1334)463806; E-mail: ads10@st-andrews.ac.uk
Received 28 April 2011
and enantioselectivity of this process is sequentially eval-
uated (Scheme 2).
Abstract: The ability of a chiral isothiourea to promote the regio-
and enantioselective O- to C-carboxyl transfer of a series of 3-alkyl-
5-aryl- and 5-methyl-3-phenylfuranyl carbonates is examined, gen-
erating preferentially the a-regioisomers (a/g up to 83:17) with high
asymmetric induction (up to 83% ee).
OPh
previous work (Vedejs):
NMe2
N
H
O
OAc
CPh3
Key words: isothiourea, organocatalysis, carboxyl transfer, furanyl
carbonates, butenolides
Ar
O
O
O
α-isomer
OPh
Ar
O
+
O
TADMAP
(10 mol%)
O
Butenolides are a common subunit of a variety of biolog-
ically active natural products,1 with the development of
methods for the enantioselective construction of quaterna-
ry stereogenic centres within these templates via organo-
catalysis being an active area of research.
Functionalization of butenolides is commonly achieved
by derivatization of a furanyl dienolate or its equivalent;
for example, Deng and co-workers have reported the
highly diastereo- and enantioselective vinylogous aldol
reaction of 2-silyloxyfurans,2 while MacMillan and co-
workers have described the related g-functionalization of
butenolides using iminium ion catalysis.3 As an alterna-
tive strategy, Vedejs et al. have investigated the TAD-
MAP-promoted regio- and enantioselective O- to C-
carboxyl transfer of a series of 5-aryl-3-methylfuranyl
carbonates.4 In all cases, mixtures of a- and g-functional-
ized products were observed in high enantiomeric excess,
with the regioselectivity dependent upon the electronic
nature of the 5-aryl substituent; an electron-donating 4-
MeOC6H4 substituent favoured a-functionalization (a/g
91:9, 90% ee) while an electron-withdrawing 4-NCC6H4
substituent favoured g-functionalization (a/g 20:80, 90%
ee) (Scheme 1).
Building upon our ongoing interests in Lewis base5 catal-
ysis,6,7 and in particular our demonstration that chiral
isothioureas promote the O- to C-carboxyl transfer of ox-
azolyl carbonates8 with high enantioselectivity,9 herein
we probe the ability of isothiourea 110 to promote the re-
gio- and enantioselective rearrangement of a series of 3-
alkyl-5-aryl- and 5-methyl-3-phenylfuranyl carbonates.
The effect of carbonate group variation, as well as substi-
tution at C3 and C5 within these systems, upon the regio-
O
PhO
O
Ar
Ph
ee (major)
ratio α/γ
Ar
γ-isomer
60:40
91:9
20:80
up to 91%
up to 90%
up to 90%
4-MeOC6H4
4-NCC6H4
Scheme 1 Regio- and enantioselective O- to C-carboxyl transfer of
furanyl carbonates by Vedejs
OR3
R2
this work:
O
O
N
R2
R1
O
O
S
Ph
N
1
α-isomer
OR3
R1
O
R
1 = R2 = R3 = alkyl, aryl
+
O
R2
O
R3O
O
R1
γ-isomer
O
Scheme 2 Proposed isothiourea-catalyzed regio- and enantioselec-
tive O- to C-carboxyl transfer of furanyl carbonates
Model studies compared the regio- and enantioselective
rearrangements of 5-methyl-3-phenylfuranyl carbonate 4
and its isomeric 3-methyl-5-phenylfuranyl carbonate 5.
While 5 was prepared following the literature procedure,4
carbonate 4 was prepared from 211 by sequential selena-
tion and elimination to give 3, followed by carbonate for-
mation (Scheme 3).12
SYNTHESIS 2011, No. 12, pp 1865–1879
x
x.
x
x
.
2
0
1
1
Advanced online publication: 25.05.2011
DOI: 10.1055/s-0030-1260602; Art ID: C43011SS
© Georg Thieme Verlag Stuttgart · New York

1866
C. Joannesse et al.
PAPER
Ph
isothiourea 1 gave an 83:17 mixture of a/g regioisomers,
with the major a-isomer 8 isolated in 75% yield and 81%
ee (Table 1).
Ph
i. LDA, PhSeCl, THF
O
ii. m-CPBA, CH2Cl2
61% (2 steps)
O
O
O
Having demonstrated that rearrangement of 3-methyl-5-
phenylfuranyl carbonate 5 leads to higher regio- and enan-
tioselectivity than its 5-methyl-3-phenyl carbonate isomer
4, a range of 3-alkyl-5-arylfuranyl carbonates 21–31 were
prepared. Based upon literature procedures,13 these sub-
strates were accessed by alkylation of the dianion of (phe-
nylthio)acetic acid, lactonization, diastereoselective
alkylation to give 11–20 (dr typically >10:1, see Figure 2
for X-ray analysis of major diastereoisomer 11), and sub-
sequent oxidation and thermal elimination, followed by
carbonate formation giving 21–31 (Scheme 4).
2, dr ~2:1
3
KHMDS
PhOCOCl
THF, 53%
Ph
O
O
OPh
OPh
O
Ph
O
O
O
5
4
Scheme 3 Preparation of isomeric furanyl carbonates 4 and 5
X-ray crystal structure analysis of carbonate 4 confirmed
unambiguously that O- rather than C-carboxylation had
occurred under these reaction conditions (Figure 1).
i. n-BuLi (2 equiv) then
SPh
O
O
SPh
CO2H
R1
R1
O
ii. PTSA⋅H2O
toluene, MgSO4
9,10, dr 1-2:1
R1 = Ph, 4-FC6H4
LDA, DMPU, THF
R2Br, NaI or R2I
R2
R2
O
i. m-CPBA, CH2Cl2
ii. toluene, ∆
SPh
O
OR3
R1
O
Figure 1 Molecular representation of the X-ray crystal structure of
furanyl carbonate 4
R1
iii. LDA or Et3N
R3OCOCl
O
O
5, 21–31
11–20 dr >10:1
R1 = Ph, 4-FC6H4
R1 = Ph, 4-FC6H4
R2 = Bn, Me, Et
4-BrC6H4CH2, allyl
R2 = Bn, Me, Et
Treatment of 5-methyl-3-phenylfuranyl carbonate 4 with
isothiourea 1 proceeded with moderate regio- and enan-
tiocontrol, giving a 54:46 mixture of a/g regioisomers 6
and 7 in 44% ee and racemic form, respectively. However,
treatment of 3-methyl-5-phenylfuranyl carbonate 5 with
4-BrC6H4CH2, allyl
R3 = Ph, CH2CCl3
Scheme 4 Preparation of furanyl carbonate derivatives 5, 21–31
Table 1 Probing the O- to C-Carboxyl Transfer of Furanyl Carbon-
ates 4 and 5 Using Isothiourea 1
R2
OPh
O
O
N
R2
R1
O
O
S
Ph
N
α-isomer
1 (10 mol%)
OPh
R1
O
+
O
R2
Et2O, r.t.
4, R1 = Me, R2 = Ph
5, R1 = Ph, R2 = Me
O
O
PhO
R1
γ-isomer
O
Entry Carbonate R1
R2
Ph
Ratioa a/g Yieldb (%) eec (%)
1
4
Me
54:46
44 (a-6)
34 (g-7)
44 (a)
0 (g)
Figure 2 Molecular representation of the X-ray crystal structure of
11
2
5
Ph
Me
83:17
75 (a-8)
81 (a)
a As shown by 1H NMR spectroscopic analysis of the crude reaction
Optimization studies probed the regio- and enantioselec-
tive rearrangement of 3-benzyl-5-phenylfuranyl phenyl
carbonate (21) catalyzed by isothiourea 1. At room tem-
perature in dichloromethane, isothiourea 1 gave a 63:37
product.
b Isolated yield of either major a-regioisomer (a) or minor g-regioiso-
mer (g).
c Determined by chiral HPLC analysis.
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

PAPER
Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1867
ratio of a/g products, with purification giving the major a- the specific rotation and HPLC retention times of a sam-
isomer 32 in 54% yield and 80% ee (Table 2, entry 1). No ple of (S)-8 that was prepared by rearrangement of 5 with
improvement in enantiomeric excess, and a noticeable de- (R)-TADMAP.15 This indicates that chiral isothiourea 1
crease in reactivity,14 was observed upon cooling the reac- generates the same sense of asymmetric induction in this
tion temperature, while changing solvent gave a marginal preferential a-regioselective carboxyl transfer process as
improvement in regiocontrol and enantioselectivity at observed previously in the analogous O- to C-carboxyl
room temperature. Under optimal conditions, rearrange- transfer process of oxazolyl carbonates.9
ment of 21 using isothiourea 1 in diethyl ether at room
We assume this process is initiated by nucleophilic attack
of the isothiourea to the furanyl carbonate carbonyl, gen-
erating a furanyl dienolate and N-carboxyl isothiouroni-
um ion, with C-carboxylation of the dienolate at either the
temperature gave a 75:25 regioisomeric a/g ratio, with the
major a-isomer 32 isolated in 70% yield and 83% ee (en-
try 5). Rearrangement of the trichloroethyl carbonate 22
gave a 50:50 mixture of a/g products 33 and 34 (entry 6)
a- or g-position generating the observed C-carboxyl prod-
with reduced enantioselectivity in comparison with phe-
ucts (Scheme 5).
nyl carbonate 21, consistent with variation of the carbon-
ate group influencing both regio- and enantiocontrol in
this series.
R2
OPh
N
O
O
Table 2 Isothiourea 1 Promoted O- to C-Carboxyl Transfer of 21
and 22
S
Ph
R1
N
R2
O
O
α-isomer
OR
Bn
or
R2
OPh
R1
N
O
O
O
O
N
Ph
O
Bn
O
O
PhO
O
R1
γ-isomer
O
R2
S
Ph
N
α-isomer
1 (10 mol%)
OR
+
Ph
O
Bn
O
S
R1
furanyl dienolate
O
solvent, temp
Ph
PhO
N
O
O
21, R = Ph
22, R = CH2CCl3
O
O
RO
O
Ph
N-carboxyl isothiourea
γ-isomer
Scheme 5 Assumed mechanism for the asymmetric O- to C-
carboxyl transfer of furanyl carbonates with chiral isothiourea 1
Entry Solvent
R
Ratioa a/g Yieldb (%)
eec (%)
80 (a)
71 (a)
80 (a)
79 (a)
83 (a)
1
2
3
4
5
6
CH2Cl2
CH2Cl2
toluene
THF
Ph
Ph
Ph
Ph
Ph
63:37
68:32
75:25
75:25
75:25
54 (a-32)
59 (a-32)
64 (a-32)
62 (a-32)
70 (a-32)
By analogy to our previous transition state modelling for
the analogous O- to C-carboxyl transfer process of ox-
azolyl carbonates, a simple model to account for the high
enantioselectivity observed for a-functionalization in the
O- to C-carboxyl transfer of furanyl carbonates is sche-
matically outlined below (Scheme 6).9 This model as-
sumes the N-carboxyl group of the isothiouronium
intermediate lies co-planar with the heterocycle, forcing
the adjacent C2-phenyl unit pseudoaxial in order to mini-
mize 1,2-strain.16 Preferential a-C-carboxylation of the
dienolate subsequently takes place anti- to this stereodi-
recting axial unit, through a transition state such as 46, in
which interactions with the axial C3-H of the tetrahydro-
pyrimidinium ion are minimized. Although this simple
model accounts for the observed sense of induction ob-
served for the major a-isomer in the majority of these
transformations, this rationale cannot account for the re-
duced level of regio- and enantioselectivity noted in the
rearrangement of 5-methyl-3-phenylfuranyl carbonate 4,
nor the low enantioselectivity observed for formation of
the minor g-isomer in these rearrangement processes.
However, the lower enantioselectivity observed upon re-
arrangement of 4 is consistent with the typically moderate
enantioselectivity observed upon rearrangement of the
analogous C4-aryl substituted oxazolyl carbonates.4,8j
d
Et2O
Et2O
CH2CCl3 50:50
44 (a-33)
39 (g-34)
62 (a)
26 (g)
a As shown by 1H NMR spectroscopic analysis of the crude reaction
product.
b Isolated yield of either major a-regioisomer (a) or minor g-regioiso-
mer (g).
c Determined by chiral HPLC analysis.
d Reaction temperature –78 °C to r.t.
The full scope and generality of the asymmetric process
was next investigated (Table 3). Consistent trends within
this series indicate that 3-alkyl-5-arylfuranyl phenyl car-
bonates rearrange with higher regio- and enantioselectiv-
ity [a/g up to 79:21; up to 81% ee (a)] than the
corresponding trichloroethyl carbonate derivatives [up to
59:41, up to 71% ee (a)]. Reasonable levels of asymmetric
induction (76–83% ee) are observed for the major a-iso-
mer, with only modest enantiodiscrimination observed for
the minor g-isomer. The absolute configuration of 8 ob-
tained using isothiourea 1 was assigned by comparison of
In conclusion, we have shown that isothiourea 1 promotes
the O- to C-carboxyl transfer of furanyl carbonates with
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

1868
C. Joannesse et al.
PAPER
these studies:
Reactions involving moisture-sensitive reagents were carried out
under an argon atmosphere using standard vacuum line techniques.
All glassware used was flame dried and cooled under vacuum. Sol-
vents (THF, CH2Cl2, toluene, hexane, and Et2O) were obtained an-
hydrous and purified by an alumina column (Mbraun SPS-800). PE
is defined as petroleum ether 40–60 °C. All other solvents and com-
mercial reagents were used as supplied without further purification
unless stated otherwise. Room temperature (r.t.) refers to 20–25 °C.
Temperatures of 0 °C and –78 °C were obtained using ice/water and
CO2(s)/acetone baths, respectively. Temperatures of 0 °C to –50 °C
were obtained using an immersion cooler (Haake EK 90). Reflux
conditions were obtained using an oil bath equipped with a contact
thermometer. In vacuo refers to the use of a Büchi Rotavapor R-
2000 rotary evaporator with a Vacubrand CVC2 vacuum controller
or a Heidolph Laborota 4001 rotary evaporator with a vacuum con-
troller. Analytical TLC was performed on pre-coated aluminium
plates (Kieselgel 60 F254 silica). TLC visualisation was carried out
with UV (254 nm), followed by staining with a 1% aq KMnO4 soln.
Flash column chromatography was performed on Kieselgel 60 sili-
ca in the solvent system stated.
OR3
R2
R2
isothiourea 1
O
(10 mol%)
O
O
OR3
R1
Et2O, r.t.
R1
O
O
O
α-isomer
pseudoaxial
up to 83% ee
R1
O
H
O
O
H
N
R1
R2
Ph
N
S
Ar
O
N
S
N
pseudoaxial
PhO
O
O
O
R2
Ar
46
Scheme 6 Proposed simplistic model for the asymmetric O- to C-
carboxyl transfer of furanyl carbonates with chiral isothiourea 1
preferential a-regiocontrol (up to 83:17) and with good
levels of enantiocontrol (up to 83% ee). Ongoing studies
within this laboratory are directed toward the demonstra-
tion of alternative catalytic asymmetric reaction protocols
using isothioureas and other Lewis bases in asymmetric
catalysis.
1H and 13C NMR spectra were acquired on either a Bruker Avance
1
300 (300 MHz, H, 75 MHz 13C) or a Bruker Avance II 400 (400
MHz, 1H, 100 MHz 13C) spectrometer at r.t. in the deuterated sol-
vent stated with the residual solvent as the internal standard. Infra-
red spectra were recorded on a Perkin-Elmer Spectrum GX FT-IR
spectrophotometer using either thin films on NaCl plates or KBr
Table 3 Isothiourea 1 Promoted O- to C-Carboxyl Transfer of Furanyl Carbonates 5 and 21–31
N
OR3
R2
R2
R2
O
O
S
Ph
N
O
O
1 (10 mol%)
+
OR3
R1
O
R3O
R1
O
O
Et2O, r.t.
Ar
γ-isomer
O
O
α-isomer
5, 21–31
Entry
Substrate
R1
R2
R3
Ratioa a/g
83:17
Yieldb (%)
75 (a-8)
eec (%)
81 (a)
83 (a)
1
2
3
5
Ph
Ph
Ph
Me
Bn
Bn
Ph
Ph
21
22
75:25
70 (a-32)
CH2CCl3
50:50
44 (a-33)
39 (g-34)
62 (a)
26 (g)
4
5
6
23
24
25
4-FC6H4
4-FC6H4
4-FC6H4
Bn
Me
Me
Ph
80:20
79:21
59:41
64 (a-35)
64 (a-36)
83 (a)
81 (a)
Ph
CH2CCl3
49 (a-37)
27 (g-38)
71 (a)
0 (g)
7
8
26
27
28
29
30
Ph
Et
Et
Ph
Ph
Ph
Ph
Ph
64:36
62:38
76:24
80:20
72:28
39 (a-39)
55 (a-40)
57 (a-41)
66 (a-42)
83 (a)
81 (a)
82 (a)
81 (a)
4-FC6H4
Ph
9
4-BrBn
4-BrBn
allyl
10
11
4-FC6H4
Ph
56 (a-43)
16 (g-44)
81 (a)
16 (g)
12
31
4-FC6H4
allyl
Ph
75:25
62 (a-45)
76 (a)
a As shown by 1H NMR spectroscopic analysis of the crude reaction product.
b Isolated yield of either major a-regioisomer (a) or minor g-regioisomer (g).
c Determined by chiral HPLC analysis.
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

PAPER
Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1869
discs. Only the characteristic peaks are quoted. Melting points were
recorded on an Electrothermal apparatus and are uncorrected.
HPLC analyses were obtained on a Gilson HPLC consisting of a
Gilson 305 pump, Gilson 306 pump, Gilson 811C dynamic mixer,
Gilson 805 manometric module, Gilson 401C dilutor, Gilson
213XL sample injector and sample detection was performed with a
Gilson 118 UV/vis detector. Separation was achieved using a
Chiralcel OD-H, Chiralpak AD-H, or Chiralpak AS-H column. MS
data were acquired by electrospray ionisation (ESI), electron impact
(EI) or nanospray ionisation (NSI) either at the University of St An-
drews or the EPSRC National Mass Spectrometry Service Centre,
Swansea. At the University of St Andrews, low and high resolution
ESI MS were carried out on a Micromass LCT spectrometer. At the
EPSRC National Mass Spectrometry Service Centre, low resolution
NSI MS was carried out on a Micromass Quattro II spectrometer
and high resolution NSI MS on a Thermofisher LTQ Orbitrap XL
spectrometer. Optical rotations were measured on a Perkin Elmer
Precisely/Model-341 polarimeter operating at the Na D line with a
100-mm path cell.
cooled to –78 °C and a soln of butenolide (1 equiv) in THF was add-
ed dropwise. After 30 min the dienolate soln was added dropwise to
a soln of the requisite chloroformate (1.3 equiv) in THF at –78 °C
then allowed to warm to r.t. The mixture was poured into 0.5 M
HCl, and extracted with Et2O (3 ×). The organic fraction was
washed with brine, dried (MgSO4), filtered, and concentrated in
vacuo.
General Lewis Base Promoted Rearrangement; General Proce-
dure E
To a soln of carbonate (1 equiv) in THF (~1 mL per 100 mg of car-
bonate) was added isothiourea 1 (10 mol%). The mixture was
stirred for 1 h, then concentrated in vacuo.
Alternative Preparation of Carbonates; General Procedure F
To a soln of butenolides in THF at 0 °C was added Et3N. After 15
min, the requisite chloroformate was added dropwise then allowed
to warm to r.t. overnight. The mixture was poured into H2O and ex-
tracted with Et2O (3 ×). The combined organic extracts were
washed with aq 0.1 M HCl, aq sat. NaHCO3, and brine, dried
(MgSO4), filtered, and concentrated in vacuo.
Crystallographic data (excluding structure factors) for compounds
4 and 11 have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers CCDC 822214
and 822213. Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
[fax: +44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
5-Methyl-3-phenyldihydrofuran-2(3H)-one (2)
Phenylacetic acid (12.0 g, 88.1 mmol) in THF (80 mL) was slowly
added at –78 °C to a solution of LDA (176 mmol, 2 equiv) in THF
(40 mL). The mixture was stirred for 30 min at 0 °C and cooled
again to –78 °C. The dianion mixture was added at –78 °C via can-
nula to a flask containing 2-methyloxirane (6.17 mL, 88.1 mmol)
and LiCl (3.74 g, 88.1 mmol) in THF (80 mL) and then the mixture
was stirred for 16 h at r.t. The reaction was quenched with H2O and
the mixture extracted with Et2O (3 ×). The aqueous layer was acid-
ified under ice-bath cooling by careful addition of concd HCl and
then extracted with EtOAc (3 ×). The organic layers were washed
with brine, dried (MgSO4), filtered, and concentrated in vacuo to
give a residue which gave, after chromatographic purification
(EtOAc–PE, 25:75), an inseparable mixture of both diastereomers
of lactone ( )-2 (13.25 g, 85%) as a colourless oil. Data are in ac-
cordance with the literature.7b
Butyrolactones; General Procedure A
To a soln of i-Pr2NH (2.21 equiv) in THF at 0 °C was added 2.5 M
n-BuLi in hexanes (2.21 equiv). After 15 min, the soln of LDA was
cooled to –78 °C and (phenylthio)acetic acid (1 equiv) was added as
a soln in THF. After 1 h, the requisite epoxide (1.20 equiv) was add-
ed in one portion and the mixture was allowed to warm to r.t. over
16 h. The mixture was quenched with H2O and extracted with Et2O
(3 ×). The aqueous layer was acidified with aq 10 M HCl and ex-
tracted with EtOAc (3 ×) and the combined organic extracts were
washed with brine, dried (MgSO4), filtered, and concentrated in
vacuo. The hydroxy acid formed was converted into the butyrolac-
tone by stirring in toluene with catalytic PTSA·H2O (~1 mol%) at
r.t. for 16 h followed by concentration in vacuo.
1H NMR (400 MHz, CDCl3): d = 1.52 (d, J = 5.6 Hz, 3 H, CH3), 1.55
(d, J = 6.1 Hz, 3 H, CH3), 2.00–2.14 (m, 1 H, CH), 2.33–2.45 (m, 1
H, CH), 2.52–2.64 (m, 1 H, CH), 2.77–2.87 (m, 1 H, CH), 3.89–4.02
(m, 2 H, CH), 4.61–4.74 (m, 1 H, CH), 4.79–4.91 (m, 1 H, CH),
7.28–7.45 (m, 10 H, HAr).
Alkylation of Butyrolactones; General Procedure B
To a soln of i-Pr2NH (1.3 equiv) in THF at 0 °C was added 2.5 M n-
BuLi in hexanes (1.3 equiv). After 15 min, the soln of LDA was
cooled to –78 °C and a soln of the requisite lactone (1 equiv) in THF
was added over 15 min. After 30 min, a soln of the requisite halide
(1.1 equiv) in DMPU was added in one portion and the mixture al-
lowed to warm to r.t. over 16 h. The reaction was quenched with sat.
aq NH4Cl and extracted with Et2O (3 ×). The combined organic ex-
tract was washed with H2O and brine, dried (MgSO4), filtered, and
concentrated in vacuo.
5-Methyl-3-phenylfuran-2(5H)-one (3)
To a cooled (0 °C) soln of i-Pr2NH (6.74 mL, 47.7 mmol) in THF
(75 mL) was added 2.5
M n-BuLi in hexanes (6.74 mL,
50.0 mmol). After 20 min at 0 °C, the LDA soln was cooled to –78
°C, and a soln of lactone ( )-2 (8.00 g, 45.5 mmol) in THF (15 mL)
was added. The reaction temperature was maintained at –78 °C for
30 min, and a soln of PhSeCl (13.1 g, 68.2 mmol) in THF (40 mL)
was added. The resultant mixture was slowly allowed to warm to r.t.
(over 2 h), diluted with EtOAc, washed with sat. aq NH4Cl, dried
(MgSO4), filtered, and concentrated in vacuo. Chromatographic pu-
rification (CH2Cl2–PE, 50:50) gave the selenyl intermediate as a
white solid, which was used immediately without characterisation.
To a cooled (0 °C) soln of the phenylselenyl intermediate in CHCl3
(75 mL) was added m-CPBA (70% purity, 16.8 g, 68.2 mmol) por-
tionwise at 0 °C and the mixture was allowed to warm to r.t. over 15
min. A further portion of CHCl3 (75 mL) was added along with 5%
aq Na2CO3 (150 mL). The layers were separated, the organic phase
was washed with 5% aq Na2CO3 (150 mL), dried (MgSO4), filtered,
and concentrated in vacuo. Chromatographic purification (EtOAc–
PE, 15:85) gave butenolide ( )-3 (4.86 g, 61%) as a white solid; mp
45–46 °C [Lit.12 45–46 °C]. Data are in accordance with the litera-
ture.12
Note: If using a reactive alkyl halide, such as BnBr, only DMPU
was required to promote the alkylation. If not activated, Finklestein
catalysis should be employed using NaI (0.2–1 equiv).
Butenolides; General Procedure C
To a soln of lactone (1 equiv) in CHCl3 at 0 °C was added m-CPBA
(1 equiv) portionwise. After 1 h, sat. aq NaHCO3 (excess) was add-
ed and the soln was extracted with EtOAc (3 ×). The combined or-
ganic extract was washed with brine, dried (MgSO4), filtered, and
concentrated in vacuo to afford the crude sulfoxide. The crude sulf-
oxide was dissolved in toluene and heated at reflux for 16 h before
concentration in vacuo.
Carbonates; General Procedure D
To a soln of i-Pr2NH (1.3 equiv) in THF at 0 °C was added 2.5 M
n-BuLi in hexanes (1.3 equiv). After 15 min, the soln of LDA was
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1H NMR (400 MHz, CDCl3): d = 1.45 (d, J = 6.8 Hz, 3 H, CH3),
5.09 (qd, J = 6.8, 1.8 Hz, 1 H, CH), 7.29–7.38 (m, 3 H, HAr), 7.47
(d, J = 1.8 Hz, 1 H, CH), 7.76–7.80 (m, 2 H, HAr).
1H NMR (400 MHz, CDCl3): d = 2.11 (d, J = 1.5 Hz, 3 H, CH3), 5.72
(q, J = 1.5 Hz, 1 H, CH), 6.97–7.00 (m, 2 H, HAr), 7.14–7.18 (m, 1
H, HAr), 7.26–7.38 (m, 5 H, HAr), 7.49–7.52 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 14.3, 53.5, 103.6, 121.0, 126.4,
127.1, 128.9, 129.0, 129.5, 134.4, 150.4, 155.2, 166.2, 172.1.
5-Methyl-3-phenylfuran-2-yl Phenyl Carbonate (4)
To a soln of butenolide ( )-3 (1 g, 5.75 mmol) in THF (45 mL) at
–78 °C was added 0.45 M KHMDS in hexanes (14.1 mL,
6.32 mmol). The soln was allowed to stir for 30 min before phenyl
chloroformate (0.80 mL, 6.32 mmol) was added in one portion and
the mixture was allowed to warm to r.t. over 1 h. The mixture was
quenched with sat. aq NH4Cl and extracted with Et2O (3 ×). The
combined organic fractions were dried (MgSO4), filtered, and con-
centrated in vacuo to give a residue which gave, after chromato-
graphic purification (EtOAc–PE, 2.5:97.5), carbonate 4 (896 mg,
53%) as a white solid; mp 72–73 °C.
MS (NSI+): m/z (%) = 312 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C18H18O4N: 312.1230;
found: 312.1230.
Compound 7
Racemic; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane, flow
rate 1 mL min–1): tR = 26.5 (R), 37.6 min (S).
IR (thin film): 3522, 3076, 2938 (C–H), 1770 (C=O), 1592 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.87 (s, 3 H, CH3), 7.01–7.05 (m,
2 H, HAr), 7.17–7.21 (m, 1 H, HAr), 7.29–7.39 (m, 5 H, HAr), 7.59 (s,
1 H, CH), 7.83–7.86 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 22.6, 84.1, 121.0, 126.6, 127.4,
128.6, 128.9, 129.6, 130.1, 132.4, 145.9, 150.2, 167.0, 170.2.
MS (NSI+): m/z (%) = 312 ([M + NH4]+, 62).
HRMS (NSI+): m/z [M + NH4]+ calcd for C18H18O4N: 312.1230;
IR (KBr): 3050, 2936 (C–H), 1790 (C=O), 1658 (Ar C=C), 1586,
1555 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.34 (d, J = 1.1 Hz, 3 H, CH3), 6.32
(br q, J = 1.1 Hz, 1 H, CH), 7.24–7.33 (m, 4 H, HAr), 7.40–7.46 (m,
4 H, HAr), 7.51–7.55 (m, 2 H, HAr).
13C NMR (75 MHz, CDCl3): d = 13.7, 106.8, 109.0, 120.8, 126.5,
126.8, 127.0, 128.9, 129.8, 131.2, 144.3, 146.4, 150.7, 151.0.
found: 312.1234.
MS (CI+): m/z (%) = 295 ([M + H]+, 100).
HRMS (CI+): m/z [M + H]+ calcd for C18H15O4: 295.0970; found:
295.0969.
Phenyl (S)-3-Methyl-2-oxo-5-phenyl-2,3-dihydrofuran-3-car-
boxylate [(S)-8]
Following general procedure E using carbonate 5 (59.0 mg, 0.200
mmol), Et2O (0.6 mL), and 1 (6.0 mg, 10 mol%) gave, after 1 h at
r.t. NMR of the crude shows a mixture a/g 83:17. and purification
by chromatography (silica gel, CH2Cl2–PE, 50:50), (S)-8 (44.0 mg,
75%) as a white solid;4 mp 62–64 °C; 81.0% ee; HPLC (Chiralpak
AS-H column, 5% i-PrOH–hexanes, flow rate 1.0 mL min–1): tR =
10.8 (S), 12.3 min (R).
[a]D20 +121.8 (c 0.60, CHCl3).
1H NMR (400 MHz, CDCl3): d = 1.82 (s, 3 H, CH3), 6.03 (s, 1 H,
CH), 7.10–7.13 (m, 2 H, HAr), 7.25–7.27 (m, 1 H, HAr), 7.38–7.42
(m, 2 H, HAr), 7.46–7.49 (m, 3 H, HAr), 7.69–7.72 (m, 2 H, HAr).
3-Methyl-5-phenylfuran-2-yl Phenyl Carbonate (5)
Following general procedure C using m-CPBA (1.17 g, 4.75 mmol)
and lactone 17 (1.35 g, 4.75 mmol) in CHCl3 (40 mL) gave the
crude sulfoxide, which was heated in toluene (40 mL). NMR crude
shows 11:1 mixture of 5H/3H isomers. Purification by chromatog-
raphy (silica gel, EtOAc–PE, 5:95–10:90) gave 3-methyl-5-phenyl-
furan-2(5H)-one (47) (0.65 g, 79%) as a white solid with
spectroscopic data in accordance with the literature.17
1H NMR (300 MHz, CDCl3): d = 2.02 (t, J = 1.8 Hz, 3 H, CH3), 5.91
(app. s, 1 H, CHPh), 7.15–7.16 (m, 1 H, CH=C), 7.27–7.30 (m, 2 H,
HAr), 7.39–7.42 (m, 3 H, HAr).
Following general procedure F using Et3N (0.95 mL, 6.84 mmol),
butenolide 47 (0.596 g, 3.42 mmol), THF (10 mL), and phenyl chlo-
roformate (0.86 mL, 6.84 mmol) gave, after purification by chroma-
tography (silica gel, CH2Cl2–PE, 10:90), 5 (0.250 g, 25%) as a white
solid; mp 96–98 °C. Spectroscopic data in accordance with the lit-
erature.4
1H NMR (400 MHz, CDCl3): d = 2.02 (s, 3 H, CH3), 6.52 (s, 1 H,
CH), 7.23–7.26 (m, 1 H, HAr), 7.30–7.32 (m, 2 H, HAr), 7.34–7.38
(m, 2 H, HAr), 7.42–7.46 (m, 2 H, HAr), 7.58–7.61 (m, 2 H, HAr).
5-Phenyl-3-(phenylthio)dihydrofuran-2(3H)-one (9)
Following general procedure A using 2.5 M n-BuLi in hexanes (52
mL, 130 mmol), i-Pr2NH (18 mL, 130 mmol), THF (170 mL), (phe-
nylthio)acetic acid (10.0 g, 59.0 mmol) in THF (50 mL), styrene ox-
ide (8.1 mL, 71.0 mmol) and PTSA·H2O (0.450 g, 2.36 mmol) in
toluene (100 mL) gave, after purification by chromatography (silica
gel, 100% CH2Cl2), an inseparable mixture of both diastereomers
(~1:1.5 dr) of lactone 9 (12.7 g, 80%).
1H NMR (300 MHz, CDCl3): d = 2.25 (ddd, J = 13.4, 11.4, 10.2 Hz,
1 H, CHH), 2.60–2.76 (m, 2 H, CH2), 3.02 (ddd, J = 13.2, 8.7, 6.2
Hz, 1 H, CHH), 4.04 (dd, J = 7.8, 4.5 Hz, 1 H, CH), 4.14 (dd, J =
11.4, 8.7 Hz, 1 H, CH), 5.39 (dd, J = 10.1, 6.0 Hz, 1 H, CH), 5.49
(t, J = 7.5 Hz, 1 H, CH), 7.17–7.20 (HAr), 7.31–7.43 (HAr), 7.60–
7.67 (HAr).
Phenyl (R)-5-Methyl-2-oxo-3-phenyl-2,3-dihydrofuran-3-car-
boxylate [(R)-6] and Phenyl 2-Methyl-5-oxo-4-phenyl-2,5-dihy-
drofuran-2-carboxylate (7)
Following general procedure E using carbonate 4 (29.4 mg, 0.1
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in THF (0.3
mL) heated at reflux overnight, after chromatographic purification
(CH2Cl2–PE, 50:50), gave 6 (13 mg, 44%) as a white solid and 7 (10
mg, 34%) as a colourless oil.
5-(4-Fluorophenyl)-3-(phenylthio)dihydrofuran-2(3H)-one (10)
Following general procedure A using n-BuLi (26.3 mL, 65.6
mmol), i-Pr2NH (9.26 mL, 65.6 mmol), THF (85 mL), (phenyl-
thio)acetic acid (5.00 g, 29.7 mmol) in THF (25 mL), 4-fluorosty-
rene oxide (4.22 mL, 35.7 mmol), and PTSA·H2O (200 mg, 1.05
mmol) in toluene (50 mL) gave, after chromatographic purification
(100% CH2Cl2), an inseparable mixture of both diastereomers of
lactone ( )-10 (6.66 g, 78%) as a white solid; mp 60–62 °C.
Compound (R)-6
Mp 56–58 °C; 15% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–
hexane, flow rate 1 mL min–1): tR = 15.8 (R), 19.4 min (S).
[a]D20 –52.0 (c 0.1, CH2Cl2).
IR (KBr): 3062, 3005 (C–H), 1895, 1767 (C=O), 1607, 1512.
1H NMR (400 MHz, CDCl3): d = 2.16–2.25 (m, 1 H, CH), 2.57–
2.71 (m, 2 H, CH), 2.97–3.04 (m, 1 H, CH), 4.02 (dd, J = 8.1, 3.7
IR (KBr): 3118, 3062, 2924 (C–H), 2854, 1809 (C=O), 1742
(C=O), 1686, 1590 cm–1.
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Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1871
Hz, 1 H, CH), 4.12 (dd, J = 11.3, 8.8 Hz, 1 H, CH), 5.35 (dd, J = 9.9,
6.3 Hz, 1 H, CH), 5.45 (dd, J = 8.8, 6.3 Hz, 1 H, CH), 7.02–7.15 (m,
5 H, HAr), 7.28–7.32 (m, 3 H, HAr), 7.38–7.42 (m, 6 H, HAr), 7.59–
7.64 (m, 4 H, HAr).
13C NMR (100 MHz, CDCl3): d = 38.3, 38.6, 45.3, 46.7, 78.4, 79.0,
115.7, 115.8, 127.3, 127.6, 128.8, 129.0, 129.4, 129.4, 131.6, 131.6,
133.7, 134.1, 134.3, 134.3, 162.8, 162.9, 174.0, 174.2.
Major diastereomer
Mp 48–50 °C.
IR (KBr): 3066, 2971 (C–H), 2941, 1765 (C=O), 1606, 1512 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.20 (t, J = 7.4 Hz, 3 H, CH2CH3),
1.96–2.07 (m, 2 H, CH2CH3), 2.35 (dd, J = 14.1, 8.4 Hz, 1 H, CH),
2.77 (dd, J = 14.1, 7.6 Hz, 1 H, CH), 5.29 (t, J = 8.0 Hz, 1 H, CH),
6.83–6.87 (m, 2 H, HAr), 6.92–6.97 (m, 2 H, HAr), 7.37–7.42 (m, 2
H, HAr), 7.45–7.50 (m, 1 H, HAr), 7.59–7.61 (m, 2 H, HAr).
MS (NSI+): m/z (%) = 306 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C16H17O2NFS: 306.0959;
found: 306.0962.
13C NMR (100 MHz, CDCl3): d = 9.4, 29.8, 41.2, 57.6, 77.0, 115.5,
127.5, 129.3, 129.9, 130.3, 135.1, 137.3, 162.6, 176.7.
MS (NSI+): m/z (%) = 334 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C18H21O2NFS: 334.1272;
3-Benzyl-5-phenyl-3-(phenylthio)dihydrofuran-2(3H)-one (11)
Following general procedure B using 2.5 M n-BuLi in hexanes (9.2
mL, 23.1 mmol), i-Pr2NH (3.2 mL, 23.1 mmol) in THF (40 mL),
lactone 9 (4.80 g, 17.8 mmol) in THF (20 mL) and, BnBr (2.7 mL,
23.1 mmol) and NaI (0.540 g, 3.60 mmol) in DMPU (11 mL) gave
crude product. NMR crude shows 6:1 mixture of diastereomers. Pu-
rification by chromatography (silica gel, CH2Cl2–PE, 20:80–100:0)
gave the major diastereomer (4.76 g, 74%) as a white solid; mp
110–112 °C.
found: 334.1274.
3-(4-Bromobenzyl)-5-(4-fluorophenyl)-3-(phenylthio)dihydro-
furan-2(3H)-one (14)
Following general procedure B using n-BuLi (5.42 mL, 13.5
mmol), i-Pr2NH (1.90 mL, 13.5 mmol), THF (10 mL), lactone ( )-
10 (3.0 mg, 10.4 mmol) in THF (10 mL), and 4-bromobenzyl bro-
mide (2.86 mL, 11.5 mmol) in DMPU (7 mL) gave a mixture of
both diastereomers of lactone ( )-14 (96:4 ratio). Chromatographic
purification (CH2Cl2–PE, 40:60) gave lactone ( )-14 (2.45 g, 51%)
as a white solid.
IR (KBr): 2978, 1770 (C=O), 1488, 1439, 1172 (C–O), 1070, 980,
752, 697 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.33 (ABX, JAB = 14.1 Hz, JAX
=
9.0 Hz, 1 H, CHH), 2.80 (ABX, JBA = 14.1 Hz, JBX = 7.5 Hz, 1 H,
CHH), 3.02 (ABq, JAB = 13.2 Hz, 1 H, CHH), 3.47 (ABq, JBA = 13.2
Hz, 1 H, CHH), 4.03 (ABX, JXA = 9.0 Hz, JXB = 7.5 Hz, 1 H, CH),
6.58–6.61 (m, 2 H, HAr), 7.11–7.22 (m, 3 H, HAr), 7.34–7.41 (m, 7
H, HAr), 7.44–7.49 (m, 1 H, HAr), 7.62–7.65 (m, 2 H, HAr).
13C NMR (75 MHz, CDCl3): d = 40.9, 43.7, 58.4, 78.2, 126.0,
128.3, 128.8, 128.9, 129.4, 129.8, 130.4, 130.5, 130.6, 135.6, 137.8,
139.4, 177.6.
Major diastereomer
Mp 104–106 °C.
IR (KBr): 3065, 2926 (C–H), 1775 (C=O), 1604, 1509 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.23 (dd, J = 14.3, 8.5 Hz, 1 H,
CH), 2.69 (dd, J = 14.3, 7.6 Hz, 1 H, CH), 2.91 (ABq, J = 13.4 Hz,
1 H, CHAHB), 3.32 (ABq, J = 13.4 Hz, 1 H, CHAHB), 4.14 (t, J = 8.1
Hz, 1 H, CH), 6.52–6.55 (m, 2 H, HAr), 6.75–6.79 (m, 2 H, HAr),
7.10–7.13 (m, 2 H, HAr), 7.30–7.34 (m, 2 H, HAr), 7.38–7.44 (m, 3
H, HAr), 7.52–7.54 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 40.2, 42.5, 57.5, 77.0, 115.4,
122.1, 127.4, 129.5, 129.9, 130.2, 131.7, 132.2, 134.1, 134.7, 137.5,
162.6, 176.7.
5-(4-Fluorophenyl)-3-methyl-3-(phenylthio)dihydrofuran-
2(3H)-one (12)
Following general procedure B using n-BuLi (5.42 mL, 13.5
mmol), i-Pr2NH (1.90 mL, 13.5 mmol), THF (10 mL), lactone ( )-
10 (3.00 g, 10.4 mmol) in THF (10 mL), and MeI (0.71 mL, 11.5
mmol) in DMPU (7 mL) gave a mixture of both diastereomers of
lactone ( )-12 (94:6 ratio). Chromatographic purification (EtOAc–
PE, 15:85), gave lactone ( )-12 (2.49 g, 79%) as a yellow solid.
MS (NSI+): m/z (%) = 476 ([M + NH4]+, 100).
HRMS (NSI+): m/z [79BrM + NH4]+ calcd for C23H22O2N79BrFS:
474.0533; found: 474.0528.
Major diastereomer
Mp 42–44 °C.
IR (KBr): 2977 (C–H), 1769 (C=O), 1488 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.69 (s, 3 H, CH3), 2.40 (dd, J =
13.7, 9.0 Hz, 1 H, CH), 2.64 (dd, J = 13.7, 7.0 Hz, 1 H, CH), 5.34
(dd, J = 9.0, 7.0 Hz, 1 H, CH), 6.92–7.01 (m, 4 H, HAr), 7.38–7.42
(m, 2 H, HAr), 7.45–7.49 (m, 1 H, HAr), 7.60–7.62 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 23.7, 44.0, 52.8, 76.6, 115.6,
127.5, 129.3, 129.9, 130.3, 134.6, 137.1, 162.7, 177.2.
3-Allyl-5-(4-fluorophenyl)-3-(phenylthio)dihydrofuran-2(3H)-
one (15)
Following general procedure B using n-BuLi (7.22 mL, 18.0 mmol)
and i-Pr2NH (2.53 mL, 18.0 mmol) in THF (10 mL), lactone ( )-10
(4.00 g, 13.9 mmol) in THF (10 mL) and allyl bromide (1.32 mL,
15.3 mmol) and NaI (0.42 g, 2.78 mmol) in DMPU (10 mL) gave a
mixture of both diastereomers of lactone ( )-15 (95:5 ratio). Chro-
matographic purification (EtOAc–PE, 10:90) gave lactone ( )-15
(2.83 g, 65%) as a white solid.
MS (NSI+): m/z (%) = 320 ([M + NH4]+, 100).
Major diastereomer
Mp 56–58 °C.
HRMS (NSI+): m/z [M + NH4]+ calcd for C17H19O2NFS: 320.1115;
found: 320.1118.
IR (KBr): 3077, 2981 (C–H), 2934, 1771 (C=O), 1640, 1607, 1513
cm–1.
3-Ethyl-5-(4-fluorophenyl)-3-(phenylthio)dihydrofuran-2(3H)-
one (13)
1H NMR (300 MHz, CDCl3): d = 2.33 (dd, J = 14.1, 8.3 Hz, 1 H,
CH), 2.64 (ABqd, J = 13.9, 7.8 Hz, 1 H, CH2=CHCHAHB), 2.76
(ABqd, J = 13.9, 6.9 Hz, 1 H, CH2=CHCHAHB), 2.81 (dd, J = 14.1,
8.0 Hz, 1 H, CH), 5.24 (t, J = 8.0 Hz, 1 H, CH), 5.31–5.33 (m, 1 H,
CHAHB=CH), 5.36–5.38 (m, 1 H, CHAHB=CH), 5.88–6.02 (m, 1 H,
CH2=CH), 6.81–6.87 (m, 2 H, HAr), 6.91–6.98 (m, 2 H, HAr), 7.39–
7.45 (m, 2 H, HAr), 7.47–7.53 (m, 1 H, HAr), 7.61–7.65 (m, 2 H,
HAr).
Following general procedure B using n-BuLi (7.22 mL, 18.0
mmol), i-Pr2NH (2.53 mL, 18.0 mmol), THF (10 mL), lactone ( )-
10 (4.00 g, 13.9 mmol) in THF (10 mL), and EtI (1.23 mL, 15.3
mmol) in DMPU (10 mL) gave a mixture of both diastereomers of
lactone ( )-13 (96:4 ratio). Chromatographic purification (EtOAc–
PE, 10:90), gave lactone ( )-13 (2.87 g, 65%) as a white solid.
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13C NMR (100 MHz, CDCl3): d = 40.8, 41.2, 56.2, 77.0, 115.5,
121.0, 127.5, 129.4, 130.0, 130.1, 131.4, 135.1, 137.4, 162.4, 176.5.
MS (ES+): m/z (%) = 316.1 (100, [M + NH4]+), 299.1 (37, [M +
H]+).
MS (NSI+): m/z (%) = 346 ([M + NH4]+, 100).
HRMS (ES+): m/z [M + NH4]+ calcd for C18H22O2NS: 316.1366;
found: 316.1367.
HRMS (NSI+): m/z [M + H]+ calcd for C19H18FO2S: 329.1006;
found: 329.1005.
3-(4-Bromobenzyl)-5-phenyl-3-(phenylthio)dihydrofuran-
2(3H)-one (19)
3-Benzyl-5-(4-fluorophenyl)-3-(phenylthio)dihydrofuran-
2(3H)-one (16)
Following general procedure B using 2.5 M n-BuLi in hexanes (5.6
mL, 13.9 mmol), i-Pr2NH (1.7 mL, 12.2 mmol) in THF (25 mL),
lactone 9 (3.00 g, 11.1 mmol) in THF (5 mL), and 4-bromobenzyl
bromide (2.78 g, 11.1 mmol) in DMPU (6.7 mL) gave crude prod-
uct. NMR crude shows 15:1 mixture of diastereomers. Purification
by chromatography (silica gel, Et2O–PE, 25:75) gave the major
diastereomer (3.00 g, 62%) as a white solid; mp 126–127 °C.
Following general procedure B using n-BuLi (5.42 mL, 13.5
mmol), i-Pr2NH (1.90 mL, 13.5 mmol), THF (10 mL), lactone ( )-
10 (3.0 mg, 10.4 mmol) in THF (10 mL) and BnBr (1.36 mL, 11.5
mmol) in DMPU (7 mL) gave a mixture of both diastereomers of
lactone ( )-16 (98:2 ratio). Chromatographic purification (EtOAc–
PE, 10:90) gave lactone ( )-16 (2.45 g, 62%) as a white solid.
IR (KBr): 2977, 1769 (C=O), 1488, 1439, 1405, 1326, 1237, 1218,
1164 (C–O), 1072, 1043, 1027, 1012, 984, 752, 696 cm–1.
Major diastereomer
Mp 82–84 °C.
1H NMR (400 MHz, CDCl3): d = 2.35 (ABX, JBA = 14.2 Hz, JBX
=
IR (KBr): 3066, 2923 (C–H), 1770 (C=O), 1607, 1509 cm–1.
8.6, 1 H, CHH), 2.77 (ABX, JAB = 14.2 Hz, JAX = 7.6 Hz, 1 H,
CHH), 2.99 (ABq, J = 13.4 Hz, 1 H, CHH), 3.39 (ABq, J = 13.4 Hz,
1 H, CHH), 4.26 (app t, J = 8.0 Hz, 1 H, CH), 6.66–6.69 (m, 2 H,
HAr), 7.15–7.22 (m, 5 H, HAr), 7.37–7.41 (m, 2 H, HAr), 7.45–7.51
(m, 3 H, HAr), 7.59–7.62 (m, 2 H, HAr).
1H NMR (300 MHz, CDCl3): d = 2.16 (dd, J = 14.2, 8.9 Hz, 1 H,
CH), 2.66 (dd, J = 14.2, 7.4 Hz, 1 H, CH), 2.88 (ABq, J = 13.2 Hz,
1 H, CHAHB), 3.35 (ABq, J = 13.2 Hz, 1 H, CHAHB), 3.86 (dd, J =
8.9, 7.4 Hz, 1 H, CH), 6.38–6.43 (m, 2 H, HAr), 6.65–6.71 (m, 2 H,
HAr), 7.17–7.37 (m, 8 H, HAr), 7.48–7.51 (m, 2 H, HAr).
13C NMR(75 MHz, CDCl3): d = 40.5, 43.3, 58.1, 77.1, 115.4, 127.4,
127.9, 129.0, 129.5, 130.0, 130.0, 130.2, 134.9, 135.2, 137.5, 162.6,
177.0.
13C NMR (100 MHz, CDCl3): d = 40.4, 42.7, 57.5, 77.8, 125.6,
128.58, 128.62, 129.5, 130.0, 130.2, 131.9, 132.2, 134.3, 137.5,
139.0, 176.9.
MS (ESI+): m/z (%) = 458 (100, [81BrM + NH4]+), 456 (97, [79BrM
+ NH4]+).
MS (NSI+): m/z (%) = 396 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C23H23O2NFS: 396.1428;
HRMS (ESI+): m/z [79BrM + NH4]+ calcd for C23H2379BrO2NS:
456.0627; found: 456.0627.
found: 396.1427.
3-Allyl-5-phenyl-3-(phenylthio)dihydrofuran-2(3H)-one (20)
Following general procedure B using 2.5 M n-BuLi in hexanes (7.7
mL, 19.2 mmol), i-Pr2NH (2.7 mL, 19.2 mmol) in THF (30 mL),
lactone 9 (4.00 g, 14.8 mmol) in THF (15 mL), and allyl bromide
(1.7 mL, 19.2 mmol) and NaI (0.450 g, 3.00 mmol) in DMPU (11
mL) gave crude product. NMR crude shows 8:1 mixture of diaste-
reomers. Purification by chromatography (silica gel, EtOAc–PE,
10:90) gave the major diastereomer (3.44 g, 75%) as a colourless
oil.
3-Methyl-5-phenyl-3-(phenylthio)dihydrofuran-2(3H)-one (17)
Following general procedure B using 2.5 M n-BuLi in hexanes (3.8
mL, 9.60 mmol), i-Pr2NH (1.4 mL, 9.60 mmol) in THF (15 mL),
lactone 9 (2.00 g, 7.40 mmol) in THF (10 mL), and MeI
(23.1 mmol, 2.7 mL) in DMPU (4.3 mL) gave crude product. NMR
crude shows 14:1 mixture of diastereomers. Purification by chroma-
tography (silica gel, CH2Cl2–PE, 50:50–100:0) gave the major dia-
stereomer (1.41 g, 67%) as a white solid; mp 42–44 °C.
1H NMR (300 MHz, CDCl3): d = 1.67 (s, 3 H, CH3), 2.42 (ABX,
JAB = 13.8 Hz, JAX = 9.2 Hz, 1 H, CHH), 2.61 (ABX, JBA = 13.6 Hz,
JBX = 6.8 Hz, 1 H, CHH), 5.34 (ABX, JXA = 9.2 Hz, JXB = 6.8 Hz, 1
H, CH), 6.95–6.97 (m, 2 H, HAr), 7.25–7.30 (m, 3 H, HAr), 7.34–
7.39 (m, 2 H, HAr), 7.41–7.46 (m, 1 H, HAr), 7.58–7.60 (m, 2 H,
HAr).
IR (thin film): 3062, 2933 (C–H), 1769 (C=O), 1439, 1325, 1172
(C–O), 1026, 995, 752, 695 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.21 (dd, J = 14.1, 8.4 Hz, 1 H,
CHCHH), 2.48 (app. dd, J = 13.9, 7.8 Hz, 1 H, CHHCH=), 2.61
(app. dd, J = 13.8, 6.8 Hz, 1 H, CHHCH=), 2.68 (app. dd, J = 14.0,
7.6 Hz, 1 H, CHCHH), 5.11 (t, J = 8.0 Hz, 1 H, CH2CH), 5.15–5.16
(m, 1 H, =CHH), 5.19–5.22 (m, 1 H, =CHH), 5.73–5.87 (m, 1 H,
=CH), 6.71–6.74 (m, 2 H, HAr), 7.07–7.14 (m, 3 H, HAr), 7.21–7.27
(m, 2 H, HAr), 7.29–7.35 (m, 1 H, HAr), 7.44–7.48 (m, 2 H, HAr).
3-Ethyl-5-phenyl-3-(phenylthio)dihydrofuran-2(3H)-one (18)
Following general procedure B using 2.5 M n-BuLi in hexanes (9.6
mL, 24.1 mmol), i-Pr2NEt (3.4 mL, 24.1 mmol) in THF (40 mL),
lactone 9 (5.00 g, 18.5 mmol) in THF (20 mL), and EtI (1.5 mL,
18.5 mmol) in DMPU (11 mL) gave crude product. NMR crude
shows 84% conversion, 9:1 mixture of diastereomers. Purification
by chromatography (silica gel, EtOAc–PE, 5:95) gave the major
diastereomer (3.53 g, 64%) as a white solid; mp 84–86 °C.
13C NMR (100 MHz, CDCl3): d = 40.9, 41.3, 56.3, 77.8, 121.0,
125.7, 128.6, 128.7, 129.4, 130.0, 130.2, 131.6, 137.4, 139.3, 176.7.
MS (ES+): m/z (%) = 328.1 (100, [M + NH4]+), 311.1 (48, [M +
H]+).
HRMS (ES+): m/z [M + NH4]+ calcd for C19H22O2NS: 328.1366;
found: 328.1368.
IR (KBr disc): 2976 (C–H), 1772 (C=O), 1458, 1323, 1180 (C–O),
1025, 958, 755, 696.
1H NMR (400 MHz, CDCl3): d = 1.19 (t, J = 7.4 Hz, 3 H, CH3), 2.00
(qd, J = 7.4, 1.6 Hz, 2 H, CH2), 2.37 (ABX, JAB = 14.0 Hz, JAX = 8.5
Hz, 1 H, CHH), 2.75 (ABX, JBA = 14.0 Hz, JBX = 7.5 Hz, 1 H,
CHH), 5.28 (t, J = 8.0 Hz, 1 H, CH), 6.89 (dd, J = 7.5, 1.8 Hz, 2 H,
HAr), 7.22–7.28 (m, 3 H, HAr), 7.36 (tt, J = 7.4, 1.6 Hz, 2 H, HAr),
7.42–7.46 (m, 1 H, HAr), 7.58 (dd, J = 8.2, 1.3 Hz, 2 H, HAr).
3-Benzyl-5-phenylfuran-2-yl Phenyl Carbonate (21)
Following general procedure C using m-CPBA (1.65 g, 5.55 mmol),
lactone 11 (2.00 g, 5.55 mmol) in CHCl3 (40 mL) gave the crude
sulfoxide, which was heated in toluene (40 mL). NMR analysis of
the crude reaction product indicates a 1:3.5 mixture of 3H/5H iso-
mers. Purification by chromatography (silica gel, EtOAc–PE, 5:95–
10:90) gave both butenolides 3-benzyl-5-phenylfuran-2-one 46 (ra-
tio 5H/3H 4:1) (1.16 g, 83%) as a white solid.
13C NMR (100 MHz, CDCl3): d = 9.5, 29.8, 41.4, 57.7, 77.7, 125.7,
128.6, 128.7, 129.3, 129.9, 130.4, 137.3, 139.4, 177.0.
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

PAPER
Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1873
Major (5H)-tautomer
lide ( )-51 (1.16 g, 4.33 mmol) in THF (15 mL) and phenyl chloro-
formate (0.72 mL, 5.63 mmol) in THF (15 mL) gave, after
chromatographic purification (EtOAc–PE, 2.5:97.5), carbonate 23
(320 mg, 19%) as a white solid; mp 100–102 °C.
1H NMR (400 MHz, CDCl3): d = 3.64–3.76 (m, 2 H, CH2), 5.90 (q,
J = 1.9 Hz, 1 H, PhCH), 6.94 (q, J = 1.9 Hz, 1 H, CH=C), 7.24–7.48
(m, 10 H, HAr).
IR (KBr): 3108 (C–H), 1795 (C=O), 1656, 1591, 1561 cm–1.
Minor (3H)-tautomer
1H NMR (300 MHz, CDCl3): d = 3.79 (s, 2 H, CH2), 6.42 (s, 1 H,
CH), 7.04–7.10 (m, 2 H, HAr), 7.25–7.38 (m, 8 H, HAr), 7.43–7.48
(m, 2 H, HAr), 7.53–7.59 (m, 2 H, HAr).
1H NMR (400 MHz, CDCl3): d = 3.20 (ddd, J = 17.5, 6.0, 3.0 Hz, 1
H, CHH), 3.72–3.77 (m, 1 H, CHH), 5.65 (dd, J = 8.3, 6.0 Hz, 1 H,
CH=C), 7.24–7.55 (m, 10 H, HAr), 7.68 (t, J = 2.9 Hz, 1 H, PhCH).
13C NMR (100 MHz, CDCl3): d = 29.9, 107.4, 108.8, 115.7, 120.7,
125.2, 126.4, 126.5, 126.7, 128.6, 128.7, 129.7, 139.0, 146.2, 146.7,
150.6, 150.8, 162.2.
MS (ES+): m/z (%) = 411 ([M + Na]+, 100).
HRMS (ES+): m/z [M + Na]+ calcd for C24H17O4NaF: 411.1009;
Following general procedure F using Et3N (0.89 mL, 6.40 mmol),
butenolide 46 (0.800 g, 3.20 mmol), THF (15 mL) and phenyl chlo-
roformate (0.84 mL, 6.40 mmol) gave, after purification by chroma-
tography (silica gel, CH2Cl2–PE, 15:85), 21 (0.595 g, 50%) as a
white solid; mp 94–96 °C.
IR (KBr): 3063 (C–H), 2924, 2858, 1796 (C=O), 1656 (ArH), 1648
(C=C), 1218 (C–O), 1194 (C–O), 1115, 1052, 760 cm–1 (furan CH).
found: 411.1008.
1H NMR (300 MHz, CDCl3): d = 3.78 (s, 2 H, CH2), 6.46 (s, 1 H,
5-(4-Fluorophenyl)-3-methylfuran-2-yl Phenyl Carbonate (24)
Following general procedure C using lactone ( )-12 (2.00 g, 6.62
mmol), m-CPBA (1.63 g, 6.62 mmol), and CHCl3 (150 mL), gave
the crude sulfoxide. Subsequent heating at reflux in toluene (50 mL)
overnight gave, after chromatographic purification (EtOAc–PE,
15:85), a mixture of both tautomers of butenolide 5-(4-fluorophe-
nyl)-3-methylfuran-2-one 52 (ratio 5H/3H 97:3) (1.06 g, 84%) as an
orange solid.
CH), 7.21–7.45 (m, 13 H, HAr), 7.56–7.59 (m, 2 H, HAr).
13C NMR (75 MHz, CDCl3): d = 30.0, 107.8, 108.8, 120.8, 123.5,
126.6, 126.8, 127.6, 128.7, 128.8, 128.8, 129.8, 130.2, 139.2, 146.4,
147.6, 150.7, 151.0.
MS: m/z (%) = 371 (100, [M + H]+).
HRMS: m/z [M + H]+ calcd for C24H19O4: 371.1278; found:
371.1279.
Major (5H)-tautomer
Mp 30–32 °C.
3-Benzyl-5-phenylfuran-2-yl 2,2,2-Trichloroethyl Carbonate
(22)
Following general procedure F using Et3N (0.70 mL, 5.00 mmol),
butenolide 46 (0.630 g, 2.50 mmol), THF (10 mL), and 2,2,2-
trichloroethyl chloroformate (0.69 mL, 5.00 mmol) gave, after pu-
rification by chromatography (silica gel, CH2Cl2–PE, 15:85), 22
(0.490 g, 46%) as a white solid; mp 92–94 °C.
IR (thin film): 2924 (C–H), 2852, 1760 (C=O), 1606 (Ar C=C),
1509 cm–1 (C=C).
1H NMR (400 MHz, CDCl3): d = 2.03 (t, J = 1.8 Hz, 3 H, CH3), 5.87
(app t, J = 1.8 Hz, 1 H, CH), 7.08–7.13 (m, 3 H, HAr, CH), 7.25–7.29
(m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 10.6, 81.5, 115.9, 128.5, 129.8,
131.0, 148.2, 163.0, 174.1.
IR (KBr disc): 2965 (C–H), 1792 (C=O), 1655 (C=C), 1283 (C–O),
1208 (C–O), 758 (C–Cl), 712 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 2 H, CH2Ph), 4.87 (s, 2 H,
CH2CCl3), 6.45 (s, 1 H, CH), 7.21–7.38 (m, 8 H, HAr), 7.54–7.58
(m, 2 H, HAr).
MS (NSI+): m/z (%) = 318 ([M + H]+, 100).
HRMS (NSI+): m/z [M + H]+ calcd for C11H10FO2: 193.0659; found:
193.0658.
13C NMR (75 MHz, CDCl3): d = 29.9, 77.9, 93.8, 107.8, 108.8,
Following general procedure D using i-Pr2NH (0.71 mL, 5.08
mmol) and n-BuLi (2.03 mL, 5.08 mmol) in THF (15 mL), buteno-
lide ( )-52 (750 mg, 3.91 mmol) in THF (15 mL), and phenyl chlo-
roformate (0.65 mL, 5.08 mmol) in THF (15 mL) gave, after
chromatographic purification (EtOAc–PE, 2.5:97.5), 24 (944 mg,
84%) as a white solid; mp 63–65 °C.
123.5, 126.6, 127.7, 128.7, 128.8, 130.1, 139.1, 146.1, 147.7, 151.4.
3-Benzyl-5-(4-fluorophenyl)furan-2-yl Phenyl Carbonate (23)
Following general procedure C using lactone ( )-16 (2.30 g, 6.09
mmol), m-CPBA (1.50 g, 6.09 mmol), and CHCl3 (150 mL) gave
the crude sulfoxide. Subsequent heating at reflux in toluene (50 mL)
overnight gave, after chromatographic purification (EtOAc–PE,
10:90), a mixture of both tautomers of butenolide 3-benzyl-5-(4-
fluorophenyl)furan-2-one 51 (ratio 5H/3H 81:19) (1.28 g, 78%) as
a yellow oil.
IR (KBr): 3059, 2935 (C–H), 1794 (C=O), 1659, 1597, 1561 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.04 (s, 3 H, CH3), 6.48 (s, 1 H,
CH), 7.06–7.11 (m, 2 H, HAr), 7.31–7.35 (m, 3 H, HAr), 7.45–7.49
(m, 2 H, HAr), 7.57–7.60 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 8.6, 104.9, 108.4, 115.7, 120.7,
125.1, 126.6, 126.7, 129.7, 146.2, 146.2, 150.6, 150.9, 162.1.
Major (5H)-tautomer
IR (thin film): 3501, 3064, 3030, 2917 (C–H), 1760 (C=O), 1655,
MS (ES+): m/z (%) = 335 ([M + Na]+, 64).
HRMS (ES+): m/z [M + Na]+ calcd for C18H13O4NaF: 335.0696;
1606 (Ar C=C), 1512 cm–1 (C=C).
1H NMR (300 MHz, CDCl3): d = 3.71 (s, 2 H, CH2Ph), 5.89–5.90
(m, 1 H, CH), 6.93 (q, J = 1.7 Hz, 1 H, HAr), 7.05–7.16 (m, 2 H, HAr),
7.20–7.42 (m, 6 H, HAr, CH), 7.44–7.55 (m, 1 H, HAr).
13C NMR (75 MHz, CDCl3): d = 31.8, 81.7, 116.0, 127.0, 128.4,
128.9, 128.9, 130.8, 134.3, 137.2, 148.4, 163.1, 171.9.
MS (NSI+): m/z (%) = 286 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C17H17O2NF: 286.1238;
found: 335.0699.
5-(4-Fluorophenyl)-3-methylfuran-2-yl 2,2,2-Trichloroethyl
Carbonate (25)
Following general procedure D using i-Pr2NH (0.73 mL, 5.21
mmol) and n-BuLi (2.08 mL, 5.21 mmol) in THF (15 mL), buteno-
lide 52 (770 mg, 4.01 mmol) in THF (15 mL), and trichloroethyl
chloroformate (0.70 mL, 5.21 mmol) in THF (15 mL) gave, after
chromatographic purification (EtOAc–PE, 2.5:97.5), 25 (476 mg,
33%) as a white solid; mp 42–44 °C.
found: 286.1241.
Following general procedure D using i-Pr2NH (0.79 mL, 5.63
mmol) and n-BuLi (2.25 mL, 5.63 mmol) in THF (15 mL), buteno-
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

1874
C. Joannesse et al.
PAPER
IR (KBr): 3013, 2965 (C–H), 2929, 1795 (C=O), 1662, 1600, 1562
cm–1.
1H NMR (500 MHz, CDCl3): d = 1.99 (s, 3 H, CH3), 4.92 (s, 2 H,
CH2), 6.46 (s, 1 H, CH), 7.05–7.09 (m, 2 H, HAr), 7.54–7.57 (m, 2
H, HAr).
1H NMR (300 MHz, CDCl3): d = 1.13 (t, J = 7.5 Hz, 3 H, CH2CH3),
2.31 (qt, J = 7.5, 1.9 Hz, 2 H, CH2CH3), 5.79 (q, J = 1.9 Hz, 1 H,
CH), 6.97–7.03 (m, 3 H, HAr, CH), 7.15–7.19 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 11.8, 18.7, 81.6, 115.9, 128.4,
131.1, 135.9, 146.6, 163.0, 173.6.
13C NMR (125 MHz, CDCl3): d = 8.5, 77.7, 93.7, 104.9, 108.3,
115.7, 125.1, 126.5, 145.9, 146.3, 151.3, 162.2.
MS (NSI+): m/z (%) = 207 ([M + H]+, 100).
HRMS (NSI+): m/z [M + H]+ calcd for C12H12FO2: 207.0816; found:
Anal. Calcd for C14H11O4Cl3F: C, 45.7; H, 2.7. Found: C, 45.9; H,
2.6.
207.0812.
Following general procedure D using i-Pr2NH (0.86 mL, 6.15
mmol) and n-BuLi (2.46 mL, 6.15 mmol) in THF (15 mL), buteno-
lide ( )-53 (975 mg, 4.73 mmol) in THF (15 mL), and phenyl chlo-
roformate (0.79 mL, 6.15 mmol) in THF (15 mL) gave, after
chromatographic purification (EtOAc–PE, 2:98), 27 (340 mg, 22%)
as a white solid; mp 48–50 °C.
3-Ethyl-5-phenylfuran-2-yl Phenyl Carbonate (26)
Following general procedure C using m-CPBA (1.65 g, 6.70 mmol)
and lactone 18 (2.00 g, 6.70 mmol) in CHCl3 (20 mL) gave the
crude sulfoxide, which was heated in toluene (20 mL). NMR anal-
ysis of the crude reaction product indicates an 18:1 mixture of 5H/
3H isomers. Purification by chromatography (silica gel, EtOAc–PE,
5:95–10:90) gave 3-ethyl-5-phenylfuran-2(5H)-one (48) (1.32 g,
64%) as a pinkish oil.
IR (KBr): 3080, 2935 (C–H), 2880, 1797 (C=O), 1655, 1594 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25 (t, J = 7.6 Hz, 3 H, CH3), 2.46
(q, J = 7.6 Hz, 2 H, CH2CH3), 6.53 (s, 1 H, CH), 7.07–7.11 (m, 2 H,
HAr), 7.31–7.35 (m, 3 H, HAr), 7.45–7.49 (m, 2 H, HAr), 7.58–7.61
(m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 13.9, 16.8, 106.9, 111.1, 115.7,
120.7, 125.1, 126.6, 126.7, 129.7, 145.5, 146.4, 150.8, 150.9, 162.1.
MS (ES+): m/z (%) = 349 ([M + Na]+, 8).
HRMS (ES+): m/z [M + Na]+ calcd for C19H15O4NaF: 349.0852;
IR (thin film): 2972 (C–H), 1756 (C=O), 1456, 1327, 1146 (C–O),
1055, 965, 752, 698, 596 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.09 (t, J = 7.5 Hz, 3 H, CH3), 2.25
(dt, J = 7.5, 1.9 Hz, 1 H, CHH), 2.29 (dt, J = 7.4, 1.9 Hz, 1 H, CHH),
5.77 (q, J = 1.9 Hz, 1 H, CH), 6.98 (q, J = 1.7 Hz, 1 H, =CH), 7.14–
7.16 (m, 2 H, HAr), 7.24–7.30 (m, 3 H, HAr).
13C NMR (100 MHz, CDCl3): d = 11.9, 18.8, 82.4, 126.5, 129.0,
129.2, 135.4, 135.6, 147.0, 173.9.
found: 349.0848.
MS (ES+): m/z (%) = 206.1 (35, [M + NH4]+), 189.1 (100, [M +
3-(4-Bromobenzyl)-5-phenylfuran-2-yl Phenyl Carbonate (28)
Following general procedure C using m-CPBA (1.44 g, 8.36 mmol)
and lactone 19 (2.70 g, 6.15 mmol) in CH2Cl2 (8 mL) gave the crude
sulfoxide, which was heated in toluene (10 mL). NMR analysis of
the crude reaction product indicates a 4:1 mixture of 5H/3H iso-
mers. Purification by chromatography (silica gel, Et2O–PE, 15:85)
gave both butenolides 3-(4-bromobenzyl)-5-phenylfuran-2-one 49
(1.46 g, 72% yield) as a yellow solid.
H]+).
HRMS (ES+): m/z [M + H]+ calcd for C12H13O2: 189.0910; found:
189.0907.
Following general procedure D using 2.5 M n-BuLi in hexanes (2.5
mL, 6.32 mmol) and i-Pr2NH (2.5 mL, 6.32 mmol) in THF (20 mL),
butenolide 48 (1.50 g, 4.86 mmol) in THF (20 mL), and phenyl
chloroformate (0.79 mL, 6.32 mmol) in THF (20 mL) gave, after
purification by chromatography (silica gel, CH2Cl2–PE, 25:75), 26
(0.730 g, 48%) as a yellow oil.
Major (5H) tautomer
1H NMR (400 MHz, CDCl3): d = 3.60–3.72 (m, 2 H, CH2), 5.91 (q,
J = 1.7 Hz, 1 H, CH), 6.97 (q, J = 1.7 Hz, 1 H, =CH), 7.15–7.18 (m,
2 H, HAr), 7.23–7.25 (m, 2 H, HAr), 7.36–7.42 (m, 3 H, HAr), 7.46–
7.49 (m, 2 H, HAr).
IR (thin film): 2972 (C–H), 1796 (C=O), 1492, 1195 (C–O), 760,
692 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.15 (t, J = 7.6 Hz, 3 H, CH3), 2.36
(q, J = 7.6 Hz, 2 H, CH2), 6.49 (s, 1 H, CH), 7.14–7.38 (m, 8 H, HAr),
7.53 (dd, J = 8.4, 1.2 Hz, 2 H, HAr).
13C NMR (75 MHz, CDCl3): d = 13.9, 17.0, 107.3, 111.2, 120.8,
123.5, 126.8, 127.4, 128.8, 129.8, 130.4, 145.6, 147.3, 150.9, 151.0.
Following general procedure F using Et3N (0.40 mL, 2.72 mmol),
butenolide 46 (0.448 g, 1.36 mmol), THF (3 mL), and phenyl chlo-
roformate (0.34 mL, 2.72 mmol) gave, after purification by chroma-
tography (silica gel, CH2Cl2–PE, 5:95), 28 (0.354 g, 58%) as a white
solid; mp 92 °C.
MS (ES+): m/z (%) = 330.9 (100, [M + Na]), 302.9 (27, [M + Na –
C2H5]).
HRMS (ES+): m/z [M + Na]+ calcd for C19H16O4Na: 331.0946;
found: 331.0945.
IR (KBr): 3062 (ArH), 2924, 2858, 1797 (C=O), 1655 (ArH), 1648
(ArH), 1606 (ArH), 1594 (ArH), 1556 (ArH), 1488, 1405, 1216 (C–
O), 1194 (C–O), 1114, 1072 (ArC–Br), 1053, 1011, 930, 760 cm–1
(furan CH).
1H NMR (400 MHz, CDCl3): d = 3.71 (s, 2 H, CH2), 6.42 (s, 1 H,
CH), 7.14–7.16 (m, 2 H, HAr), 7.22–7.28 (m, 3 H, HAr), 7.28–7.32
(m, 1 H, HAr), 7.33–7.37 (m, 2 H, HAr), 7.41–7.45 (m, 4 H, HAr),
7.56–7.59 (m, 2 H, HAr).
3-Ethyl-5-(4-fluorophenyl)furan-2-yl Phenyl Carbonate (27)
Following general procedure C using lactone ( )-13 (2.50 g, 7.91
mmol), m-CPBA (1.95 g, 7.91 mmol), and CHCl3 (150 mL) gave
the crude sulfoxide. Subsequent heating at reflux in toluene (100
mL) overnight gave, after chromatographic purification (EtOAc–
PE, 10:90), a mixture of both tautomers of 3-ethyl-5-(4-fluorophe-
nyl)furan-2-one 53 (ratio 5H/3H 99:1) (1.23 g, 75%) as a yellow
solid.
13C NMR (100 MHz, CDCl3): d = 29.5, 107.5, 108.2, 120.4, 120.7,
123.5, 126.8, 127.7, 128.8, 129.8, 130.0, 130.6, 131.7, 138.1, 146.4,
147.7, 150.6, 150.8.
MS (ESI+): m/z (%) = 348 (100, [81BrM + NH4 – PhOCO]+), 346
(97, [79BrM + NH4 – PhOCO]+).
HRMS (ESI+): m/z [81BrM + NH4 – PhOCO]+ calcd for
Major (5H)-tautomer
Mp 24–26 °C.
C17H1781BrNO2:348.0417; found: 348.0416.
IR (KBr): 3080, 2974 (C–H), 2939, 1759 (C=O), 1656, 1607 (Ar
C=C), 1509 cm–1 (C=C).
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

PAPER
Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1875
3-(4-Bromobenzyl)-5-(4-fluorophenyl)furan-2-yl Phenyl Car-
bonate (29)
13C NMR (100 MHz, CDCl3): d = 29.7, 82.5, 118.1, 126.5, 129.1,
129.3, 132.5, 133.1, 135.1, 148.6, 173.6.
Following general procedure C using lactone ( )-14 (2.45 g, 5.35
mmol) and m-CPBA (1.32 g, 5.35 mmol) and CHCl3 (100 mL) gave
the crude sulfoxide. Subsequent heating at reflux in toluene (100
mL) overnight gave, after chromatographic purification (EtOAc–
PE, 10:90), a 50:50 mixture of both tautomers of 3-(4-bromoben-
zyl)-5-(4-fluorophenyl)furan-2-one 54 (ratio 5H/3H 52:48) (1.45 g,
78%) as a light-yellow solid.
MS (ES+): m/z (%) = 218.1 (77, [M + NH4]+), 201.1 (100, [M +
H]+).
HRMS (ES+): m/z [M + H]+ calcd for C13H13O2: 201.0910; found:
201.0910.
Following general procedure F using Et3N (0.99 mL, 7.12 mmol),
butenolide 50 (0.710 g, 3.56 mmol), THF (15 mL), and phenyl chlo-
roformate (0.89 mL, 7.12 mmol) gave, after purification by chroma-
tography (silica gel, CH2Cl2–PE, 15:85), 30 (0.660 g, 58%) as a
light-yellow solid; mp 44–46 °C.
5H- and 3H-Tautomers
Mp 64–66 °C.
IR (KBr): 3086, 2932 (C–H), 1741 (C=O), 1649, 1607 (Ar C=C),
1509 cm–1 (C=C).
IR (KBr disc): 2980 (C–H), 1794 (C=O), 1655 (C=C), 1492, 1196
(C–O), 990, 928, 760, 689 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.12 (ddd, J = 17.6, 6.0, 3.1 Hz,
1 H, CHAHB), 3.65–3.71 (m, 3 H, CHAHB, CH2), 5.62 (dd, J = 8.1,
6.0 Hz, 1 H, CH), 5.88–5.89 (m, 1 H, CH), 6.94 (q, J = 1.6 Hz, 1 H,
HAr), 7.06–7.23 (m, 8 H, HAr), 7.34–7.38 (m, 4 H, HAr), 7.46–7.50
(m, 2 H, HAr, CH), 7.57–7.60 (m, 3 H, HAr, CH).
1H NMR (400 MHz, CDCl3): d = 3.16 (dt, J = 6.4, 1.4 Hz, 2 H,
CH2), 5.10 (dq, J = 10.1, 1.5 Hz, 1 H, =CHH), 5.17 (dq, J = 17.1,
1.7 Hz, 1 H, =CHH), 5.93 (ddt, J = 17.9, 10.2, 6.6 Hz, 1 H,
CH=CH2), 6.52 (s, 1 H, =CH), 7.21–7.30 (m, 4 H, HAr), 7.33–7.36
(m, 2 H, HAr), 7.39–7.43 (m, 2 H, HAr), 7.57–7.60 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 31.3, 36.5, 77.6, 81.7, 115.9,
116.1, 120.9, 124.5, 124.6, 127.3, 128.4, 130.6, 130.6, 130.6, 131.4,
132.0, 132.3, 133.3, 133.7, 135.9, 136.1, 148.7, 162.8, 163.1, 171.5,
173.0.
MS (NSI+): m/z (%) = 366 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + H]+ calcd for C17H13O279BrF:347.0077;
13C NMR (75 MHz, CDCl3): d = 28.2, 107.5, 107.8, 116.4, 120.8,
123.5, 126.8, 127.5, 128.8, 129.8, 130.2, 135.2, 146.2, 147.4, 150.7,
151.0.
MS (ES+): m/z (%) = 343.1 (100, [M + Na]).
HRMS (ES+): m/z [M + Na]+ calcd for C20H16O4Na: 343.0946;
found: 343.0952.
found: 347.0086.
3-Allyl-5-(4-fluorophenyl)furan-2-yl Phenyl Carbonate (31)
Following general procedure C using lactone 15 (2.63 g, 8.38
mmol) and m-CPBA (2.07 g, 8.38 mmol) and CHCl3 (150 mL) gave
the crude sulfoxide. Subsequent heating at reflux in toluene (100
mL) overnight gave, after chromatographic purification (EtOAc–
PE, 10:90), a mixture of both tautomers of 3-allyl-5-(4-fluorophe-
nyl)furan-2-one 55 (ratio 5H/3H 62:38) (1.25 g, 68%) as a yellow
solid.
Following general procedure D using i-Pr2NH (0.42 mL, 3.00
mmol) and n-BuLi (1.20 mL, 3.00 mmol) in THF (10 mL), buteno-
lide 54 (800 mg, 2.31 mmol) in THF (10 mL), and phenyl chloro-
formate (0.38 mL, 3.00 mmol) in THF (10 mL) gave, after
chromatographic purification (CH2Cl2–PE, 20:80), 29 (93 mg, 9%)
as a white solid; mp 64–66 °C.
IR (KBr): 3098 (C–H), 3060, 2919, 1792 (C=O), 1651, 1599, 1561
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.62 (s, 2 H, CH2), 6.27 (s, 1 H,
CH), 6.94–6.98 (m, 2 H, HAr), 7.05–7.07 (m, 2 H, HAr), 7.14–7.17
(m, 2 H, HAr), 7.20–7.24 (m, 1 H, HAr), 7.33–7.37 (m, 4 H, HAr),
7.43–7.47 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 29.4, 107.1, 108.2, 115.7, 120.4,
120.6, 125.2, 126.3, 126.8, 129.8, 130.5, 131.7, 138.0, 146.3, 146.8,
150.6, 150.8, 162.2.
Major (5H)-tautomer
IR (thin film): 3082, 3012, 2982 (C–H), 2913, 1761 (C=O), 1656,
1607 (Ar C=C), 1509 cm–1 (C=C).
1H NMR (400 MHz, CDCl3): d = 3.12–3.15 (m, 2 H, CH2CH=CH2),
5.18–5.25 (m, 2 H, CH2CH=CH2), 5.88–5.98 (m, 2 H, CH,
CH2CH=CH2), 7.07–7.14 (m, 3 H, HAr), 7.25–7.29 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 29.6, 81.7, 116.0, 118.1, 128.4,
130.8, 132.8, 132.8, 148.1, 163.1, 173.2.
MS (CI+): m/z (%) = 467 ([M + H]+, 100).
HRMS (CI+): m/z [M + H]+ calcd for C24H17O479BrF: 467.0294;
MS (NSI+): m/z (%) = 219 ([M + H]+, 100).
found: 467.0294.
HRMS (NSI+): m/z [M + H]+ calcd for C13H12FO2: 219.0816; found:
219.0812.
3-Allyl-5-phenylfuran-2-yl Phenyl Carbonate (30)
Following general procedure D using i-Pr2NH (0.90 mL, 6.39
mmol) and n-BuLi (2.56 mL, 6.39 mmol) in THF (15 mL), buteno-
lide ( )-55 (1.07 g, 4.92 mmol) in THF (15 mL), and phenyl chlo-
roformate (0.81 mL, 6.39 mmol) in THF (15 mL) gave, after
chromatographic purification (EtOAc–PE, 2.5:97.5), 31 (244 mg,
15%) as a white solid; mp 35–37 °C.
Following general procedure C using m-CPBA (2.38 g, 9.66 mmol)
and lactone 20 (2.38 g, 9.66 mmol) in CHCl3 (40 mL) gave the
crude sulfoxide, which was heated in toluene (40 mL). NMR anal-
ysis of the crude reaction product indicates a 1:3.5 mixture of 3H/
5H isomers. Purification by chromatography (silica gel, EtOAc–PE,
5:95–10:90) gave 3-allyl-5-phenylfuran-2(5H)-one (50) (1.52 g,
79%) as a yellow oil.
IR (KBr): 3102, 3061, 2974 (C–H), 1789 (C=O), 1641, 1597, 1561
cm–1.
1H NMR (500 MHz, CDCl3): d = 3.09 (d, J = 6.3 Hz, 2 H,
CH2CH=CH2), 5.05 (d, J = 10.0 Hz, 1 H, CH2CH=CHH), 5.11 (d,
Major (5H)-tautomer
IR (thin film): 3082 (C–H), 1758 (C=O), 1455, 1296, 1186 (C–O),
1047, 921, 754, 699 cm–1.
J = 17.0 Hz,
1 H, CH2CH=CHH), 5.82–5.90 (m, 1 H,
1H NMR (400 MHz, CDCl3): d = 3.08 (ddt, J = 6.7, 3.2, 1.6 Hz, 2
H, CH2), 5.15 (dq, J = 2.6, 1.3 Hz, 1 H, =CHH), 5.16 (dq, J = 24.6,
1.4 Hz, 1 H, =CHH), 5.83–5.93 (m, 2 H, CH2=CH, CHPh), 7.10 (q,
J = 1.7 Hz, 1 H, =CH), 7.22–7.24 (m, 2 H, HAr), 7.32–7.39 (m, 3 H,
HAr).
CH2CH=CH2), 6.39 (s, 1 H, CH), 6.98 (t, J = 8.5 Hz, 2 H, HAr),
7.18–7.24 (m, 3 H, HAr), 7.36 (t, J = 7.7 Hz, 2 H, HAr), 7.47–7.50
(m, 2 H, HAr).
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

1876
C. Joannesse et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 28.0, 107.4, 107.5, 115.7, 116.4,
120.7, 125.2, 126.5, 126.7, 129.7, 135.0, 146.1, 146.5, 150.6, 150.8,
162.2.
MS (ES+): m/z (%) = 361 ([M + Na]+, 100).
HRMS (ES+): m/z [M + Na]+ calcd for C20H15O4NaF:361.0852;
[a]D20 +18.2 (c 0.57, CHCl3).
IR (KBr disc): 3064 (C–H), 1762 (br, 2 C=O), 1192 (C–O), 1063,
1034, 710 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.62 (ABX, JAB = 16.9 Hz, JAX
1.7 Hz, 1 H, CHH), 3.69 (ABX, JBA = 16.9 Hz, JBX = 1.6 Hz, 1 H,
CHH), 4.71 (ABq, JAB = 11.9 Hz, 1 H, OCHH), 4.82 (ABq, JBA
=
found: 361.0841.
=
11.8 Hz, 1 H, OCHH), 7.22–7.24 (m, 2 H, HAr), 7.27–7.30 (m, 2 H,
CH, HAr), 7.32–7.36 (m, 2 H, HAr), 7.39–7.41 (m, 3 H, HAr), 7.48–
7.51 (m, 2 H, HAr).
Phenyl (S)-3-Benzyl-2-oxo-5-phenyl-2,3-dihydrofuran-3-car-
boxylate [(S)-32]
Following general procedure E using carbonate 21 (37 mg, 0.10
mmol) and chiral isothiourea 1 (3.1 mg, 10 mol%) in Et2O (0.4 mL)
for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50), the a-product 32 (26 mg, 70%) as a white solid; mp 110–112
°C; 83% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane,
flow rate 1 mL min–1): tR = 15.5 (S), 21.1 min (R).
13C NMR (100 MHz, CDCl3): d = 31.9, 74.7, 87.6, 94.1, 126.2,
127.2, 129.0, 129.0, 129.0, 129.7, 134.6, 135.7, 136.4, 146.4, 165.9,
170.9.
MS (ES+): m/z (%) = 442.0 (17, [M + NH4]+), 326.1 (100).
HRMS (ES+): m/z [M + NH4]+ calcd for C20H19O4NCl3: 442.0374;
[a]D20 +124.3 (c 0.47, CHCl3).
found: 442.0375.
IR (thin film): 1803 (C=O), 1760 (C=O), 1653 (Ar C=C), 1493,
1449, 1280, 1209, 1187 (C–O), 1159, 1127, 1073, 696, 749, 688
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.49 (ABq, J = 13.6 Hz, 1 H,
CHH), 3.64 (ABq, J = 13.6 Hz, 1 H, CHH), 5.96 (s, 1 H, =CH),
7.04–7.08 (m, 2 H, HAr), 7.22–7.27 (m, 6 H, HAr), 7.35–7.40 (m, 5
H, HAr), 7.53–7.57 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 40.9, 61.9, 101.8, 121.3, 125.4,
126.6, 127.6, 127.7, 128.6, 128.9, 129.7, 130.2, 130.5, 134.3, 150.5,
154.6, 166.4, 173.1.
Phenyl (S)-3-Benzyl-5-(4-fluorophenyl)-2-oxo-2,3-dihydrofu-
ran-3-carboxylate [(S)-35]
Following general procedure E using carbonate 23 (38.8 mg, 0.10
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in Et2O (0.4
mL) for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50), the a-product 35 (25 mg, 64%) as a white solid; mp 108–110
°C; 83% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane,
flow rate 1 mL min–1): tR = 16.8 (S), 30.6 min (R).
[a]D20 +95.0 (c 0.1, CH2Cl2).
IR (KBr): 3125, 2917 (C–H), 1804 (C=O), 1737 (C=O), 1652,
1591, 1508 cm–1.
MS (ESI+): m/z (%) = 388 (100, [M + NH4]+).
HRMS (ESI+): m/z [M + NH4]+ calcd for C24H22NO4: 388.1543;
found: 388.1543.
1H NMR (400 MHz, CDCl3): d = 3.41 (ABq, J = 13.6 Hz, 1 H, Ph-
CHAHB), 3.55 (ABq, J = 13.6 Hz, 1 H, PhCHAHB), 5.82 (s, 1 H,
CH), 6.98–7.02 (m, 4 H, HAr), 7.16–7.20 (m, 6 H, HAr), 7.28–7.32
(m, 2 H, HAr), 7.44–7.47 (m, 2 H, HAr).
13C NMR (75 MHz, CDCl3): d = 41.2, 62.2, 101.7, 116.3, 121.6,
124.1, 126.9, 127.7, 128.0, 128.9, 130.0, 130.5, 134.5, 150.7, 153.9,
164.2, 166.6, 173.2.
2,2,2-Trichloroethyl (R)-3-Benzyl-2-oxo-5-phenyl-2,3-dihydro-
furan-3-carboxylate [(R)-33] and 2,2,2-Trichloroethyl 4-Ben-
zyl-5-oxo-2-phenyl-2,5-dihydrofuran-2-carboxylate (34)
Following general procedure E using carbonate 22 (85.0 mg, 0.200
mmol), Et2O (0.6 mL), and 1 (6.0 mg, 10 mol%) gave, after 1 h at
r.t. and purification by chromatography (silica gel, CH2Cl2–PE,
50:50–100:0), the a-product 33 (37.3 mg, 44%) as a white solid and
the g-product 34 (32.8 mg, 39%) as a colourless oil which then so-
lidified as a white solid.
MS (NSI+): m/z (%) = 406 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C24H21O4NF: 406.1449;
found: 406.1448.
Phenyl (S)-5-(4-Fluorophenyl)-3-methyl-2-oxo-2,3-dihydrofu-
ran-3-carboxylate [(S)-36]
Compound (R)-33
Mp 110–112 °C; 62% ee; chiral HPLC (Chiralcel OD-H, 2% i-PrOH–
hexanes, flow rate 1.0 mL/min): tR = 14.9 (R), 16.7 min (S).
[a]D20 +74.5 (c 0.42, CHCl3).
Following general procedure E using carbonate 24 (31.2 mg, 0.1
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in Et2O (0.3
mL) for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50), the a-product 36 (20 mg, 64%) as a white solid; mp 42–44
°C; 81% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane,
flow rate 1 mL min–1): tR = 12.6 (S), 17.0 min (R).
IR (KBr disc): 2967 (C–H), 1800 (C=O), 1766 (C=O), 1495 (C=C),
1449, 1281, 1213 (C–O), 1197 (C–O), 992, 807 (C–Cl), 757, 715
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.45 (ABq, JAB = 13.6 Hz, 1 H,
CHH), 3.56 (ABq, JBA = 13.6 Hz, 1 H, CHH), 4.75 (ABq, JAB = 11.9
Hz, 1 H, OCHH), 4.88 (ABq, JBA = 11.9 Hz, 1 H, OCHH), 5.84 (s,
1 H, CH), 7.18–7.26 (m, 5 H, HAr), 7.35–7.39 (m, 3 H, HAr), 7.48–
7.51 (m, 2 H, HAr).
[a]D20 +130.0 (c 0.1, CH2Cl2).
IR (KBr): 3119, 3073, 2925 (C–H), 2854, 1805 (C=O), 1769, 1741
(C=O), 1653, 1601, 1510 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.71 (s, 3 H, CH3), 5.86 (s, 1 H,
CH), 7.00–7.09 (m, 4 H, HAr), 7.14–7.18 (m, 1 H, HAr), 7.27–7.31
(m, 2 H, HAr), 7.57–7.61 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 20.4, 56.0, 103.4, 116.1, 121.1,
123.8, 126.5, 127.4, 129.5, 150.4, 153.8, 163.9, 166.9, 174.2.
13C NMR (75 MHz, CDCl3): d = 40.4, 61.7, 74.8, 94.2, 101.3,
125.3, 127.4, 127.7, 128.6, 128.8, 130.1, 130.4, 133.9, 154.7, 166.2,
172.5.
MS (NSI+): m/z (%) = 330 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C18H17O4NF: 330.1136;
Anal. Calcd for C20H15Cl3O4: C, 56.43; H, 3.55. Found: C, 56.44; H,
3.33.
found: 330.1139.
Compound 34
Mp 94–96 °C; 26% ee; chiral HPLC (Chiralcel OD-H, 2% i-PrOH–
hexanes, flow rate 1.0 mL/min): tR = 27.2 (1), 30.1 min (2).
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

PAPER
Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1877
2,2,2-Trichloroethyl (R)-5-(4-Fluorophenyl)-3-methyl-2-oxo-
2,3-dihydrofuran-3-carboxylate [(R)-37] and 2,2,2-Trichloro-
ethyl 2-(4-Fluorophenyl)-4-methyl-5-oxo-2,5 dihydrofuran-2-
carboxylate (38)
Following general procedure E using carbonate 25 (36.8 mg, 0.1
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in Et2O (0.4
mL) for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50) the a-product 37 (18 mg, 49%) as a white solid and the g-
product 38 (10 mg, 27%) as a white solid.
Phenyl (S)-3-Ethyl-5-(4-fluorophenyl)-2-oxo-2,3-dihydrofuran-
3-carboxylate [(S)-40]
Following general procedure E using carbonate 27 (32.6 mg, 0.10
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in Et2O (0.3
mL) for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50), the a-product 40 (18 mg, 55%) as a white solid; mp 62–64
°C; 81% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane,
flow rate 1 mL min–1): tR = 11.9 (S), 13.7 min (R).
[a]D20 +138.0 (c 0.1, CH2Cl2).
IR (KBr): 3112, 3079, 2974 (C–H), 2938, 1809 (C=O), 1757
(C=O), 1653, 1602, 1509 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.98 (t, J = 7.5 Hz, 3 H, CH3), 2.22
(q, J = 7.5 Hz, 2 H, CH2CH3), 5.82 (s, 1 H, CH), 7.01–7.10 (m, 4 H,
HAr), 7.15–7.19 (m, 1 H, HAr), 7.28–7.33 (m, 2 H, HAr), 7.59–7.63
(m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 8.8, 28.1, 61.2, 101.3, 116.0,
121.2, 123.8, 126.4, 127.3, 129.5, 150.3, 153.9, 163.8, 166.5, 173.3.
MS (NSI+): m/z (%) = 344 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C19H19O4NF: 344.1293;
Compound (R)-37
71% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane, flow
rate 1 mL min–1): tR = 10.3 (R), 13.0 min (S).
[a]D20 +94.0 (c 0.1, CH2Cl2).
IR (thin film): 3112, 2962, 2938 (C–H), 2876, 1814 (C=O), 1761
(C=O), 1652, 1603, 1509 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.69 (s, 3 H, CH3), 4.67 (ABq,
J = 11.9 Hz, 1 H, CHAHBCCl3), 4.80 (ABq, J = 11.9 Hz, 1 H,
CHAHBCCl3), 5.77 (s, 1 H, CH), 7.04–7.08 (m, 2 H, HAr), 7.54–7.57
(m, 2 H, HAr).
13C NMR (125 MHz, CDCl3): d = 20.2, 55.7, 74.6, 94.2, 103.1,
116.1, 123.7, 127.4, 153.8, 163.9, 166.8, 173.7.
found: 344.1295.
Phenyl (S)-3-(4-Bromobenzyl)-2oxo-5-phenyl-2,3-dihydrofu-
ran-3-carboxylate [(S)-41]
MS (NSI+): m/z (%) = 384 ([M + NH4]+, 17).
HRMS (NSI+): m/z [35ClM + NH4]+ calcd for C14H14O4NF35Cl3:
Following general procedure E using carbonate 28 (67.5 mg,
0.200 mmol), Et2O (0.7 mL), and 1 (6.0 mg, 10 mol%) gave, after 1
h at r.t. and purification by chromatography (silica gel, CH2Cl2–PE,
50:50), the a-product 41 (38.3 mg, 57%) as a white solid; mp 150–
152 °C; 82% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–
hexanes, flow rate 1.0 mL min–1): tR = 19.8 (S), 29.2 min (R).
383.9967; found: 383.9972.
Compound 38
Mp 84–86 °C; racemic; chiral HPLC (Chiralpak AS-H, 5% i-
PrOH–hexane, flow rate 1 mL min–1): tR = 20.8 (R), 24.7 min (S).
IR (KBr): 3530, 3097, 2979 (C–H), 2929, 1777 (C=O), 1765
(C=O), 1660, 1603, 1509 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.94 (d, J = 1.5 Hz, 3 H, CH3),
4.69–4.74 (m, 2 H, CH2), 7.02–7.05 (m, 2 H, HAr), 7.43–7.44 (m, 1
H, CH), 7.46–7.49 (m, 2 H, HAr).
13C NMR (125 MHz, CDCl3): d = 10.8, 74.7, 86.6, 94.0, 116.0,
128.2, 130.6, 131.5, 145.5, 163.2, 165.8, 171.5.
[a]D20 +100.9 (c 0.53, CHCl3).
IR (KBr): 3090, 1778 (C=O), 1757 (C=O), 1591 (C=C), 1489,
1421, 1405, 1209, 1188 (C–O), 1056, 1024, 1013, 963, 913, 798,
738, 689 cm–1 (C–Br).
1H NMR (400 MHz, CDCl3): d = 3.46 (ABq, J = 13.7 Hz, 1 H,
CHH), 3.58 (ABq, J = 13.7 Hz, 1 H, CHH), 5.94 (s, 1 H, CH), 7.06–
7.09 (m, 2 H, HAr), 7.12–7.16 (m, 2 H, HAr), 7.26–7.29 (m, 1 H,
HAr), 7.37–7.43 (m, 7 H, HAr), 7.56–7.59 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 39.9, 61.7, 101.3, 121.3, 122.0,
125.5, 126.7, 127.4, 129.0, 129.8, 130.7, 131.8, 132.0, 133.3, 150.5,
155.1, 166.3, 172.9.
MS (NSI+): m/z (%) = 384 ([M + NH4]+, 35).
HRMS (NSI+): m/z [35ClM + NH4]+ calcd for C14H14O4NF35Cl3:
383.9967; found: 383.9970.
Phenyl (S)-3-Ethyl-2oxo-5-phenyl-2,3-dihydrofuran-3-carbox-
ylate [(S)-39]
MS (ESI+): m/z (%) = 466 (100, [79BrM + NH4]+), 468 (98, [81BrM
+ H]+).
Following general procedure E using carbonate 26 (61.7 mg, 0.200
mmol), Et2O (0.6 mL), and 1 (6.0 mg, 10 mol%) gave, after 1 h at
r.t. and purification by chromatography (silica gel, CH2Cl2–PE,
50:50), the a-product 39 (24.0 mg, 39%) as a sticky white solid;
83% ee; chiral HPLC (Chiralcel OD-H, 5% i-PrOH–hexanes, flow
rate 1.0 mL min–1): tR = 10.1 (S), 13.6 min (R).
HRMS (ESI+): m/z [79BrM + NH4]+ calcd for C24H2179BrNO4:
466.0648; found: 466.0641.
Phenyl (S)-3-(4-Bromobenzyl)-5-(4-fluorophenyl)-2-oxo-2,3-di-
hydrofuran-3-carboxylate [(S)-42]
Following general procedure E using carbonate 29 (46.7 mg, 0.10
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in Et2O (0.4
mL) for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50), the a-product 42 (31 mg, 66%) as a white solid; mp 110–112
°C; 81% ee; chiral HPLC (Chiralpak AS-H, 5% i-PrOH–hexane,
flow rate 1 mL min–1): tR = 20.5 (S), 39.7 min (R).
[a]D20 +86.6 (c 0.81, CHCl3).
IR (thin film): 2974 (C–H), 1794 (C=O), 1747 (C=O), 1492 (C=C),
1226, 1192 (C–O), 1096, 1076, 1012, 947, 759, 688 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.05 (t, J = 7.5 Hz, 3 H, CH3), 2.30
(q, J = 7.5 Hz, 2 H, CH2), 5.96 (s, 1 H, CH), 7.09 (dd, J = 8.6, 1.1
Hz, 2 H, HAr), 7.22–7.26 (m, 1 H, HAr), 7.37 (t, J = 7.9 Hz, 2 H, HAr),
7.44–7.47 (m, 3 H, HAr), 7.68–7.71 (m, 2 H, HAr).
[a]D20 +87.3 (c 0.15, CH2Cl2).
IR (KBr): 3127, 2925 (C–H), 1801 (C=O), 1759 (C=O), 1660,
1591, 1508 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.37 (ABq, J = 13.7 Hz, 1 H,
CHAHB), 3.49 (ABq, J = 13.7 Hz, 1 H, CHAHB), 5.78 (s, 1 H, CH),
6.98–7.06 (m, 6 H, HAr), 7.15–7.21 (m, 1 H, HAr), 7.27–7.356 (m, 4
H, HAr), 7.44–7.50 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 9.0, 28.1, 61.2, 101.8, 121.3,
125.4, 126.5, 127.7, 129.0, 129.6, 130.5, 150.5, 155.0, 166.8, 173.7.
MS (ES+): m/z (%) = 326.1 (100, [M + NH4]+), 309.1 (25, [M +
H]+).
HRMS (ES+): m/z [M + NH4]+ calcd for C19H20O4N: 326.1387;
found: 326.1389.
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

1878
C. Joannesse et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 39.8, 61.6, 100.7, 116.1, 121.1,
121.1, 123.5, 126.6, 127.4, 129.6, 131.7, 131.8, 133.1, 150.2, 154.0,
163.9, 166.0, 172.6.
MS (NSI+): m/z (%) = 486 ([M + NH4]+, 100).
HRMS (NSI+): m/z [79BrM + NH4]+ calcd for C24H20O479BrNF:
chiral HPLC (Chiralpak AS-H; 5% i-PrOH–hexane, flow rate 1
mL min–1): tR = 11.7 (S), 14.0 min (R).
[a]D20 +88.5 (c 0.2, CH2Cl2).
IR (KBr): 3081, 2923 (C–H), 1809 (C=O), 1756 (C=O), 1652,
1593, 1509 cm–1.
484.0554; found: 484.0551.
1H NMR (400 MHz, CDCl3): d = 2.85 (ABqd, J = 13.9, 7.9 Hz, 1 H,
CHHCH=CH2), 2.97 (ABqd, J = 13.9, 6.8 Hz, 1 H, CHHCH=CH2),
5.14 (d, J = 10.0 Hz, 1 H, CH2CH=CHH), 5.19–5.23 (m, 1 H,
CH2CH=CHH), 5.67–5.75 (m, 1 H, CH2CH=CH2), 5.84 (s, 1 H,
CH), 7.00–7.09 (m, 4 H, HAr), 7.16–7.20 (m, 1 H, HAr), 7.28–7.32
(m, 2 H, HAr), 7.58–7.61 (m, 2 H, HAr).
13C NMR (100 MHz, CDCl3): d = 38.9, 60.4, 101.2, 116.1, 121.0,
121.2, 123.8, 126.5, 127.4, 129.6, 130.4, 150.3, 153.8, 163.8, 166.1,
172.7.
Phenyl (S)-3-Allyl-2-oxo-5-phenyl-2,3-dihydrofuran-3-carbox-
ylate [(S)-43] and Phenyl 4-Allyl-5-oxo-2-phenyl-2,5-dihydrofu-
ran-2-carboxylate (44)
Following general procedure E using carbonate 30 (64.0 mg, 0.200
mmol), Et2O (0.6 mL), and 1 (6.0 mg, 10 mol%) gave, after 1 h at
r.t. (NMR of the crude shows a mixture a/g 72:28) and purification
by chromatography (silica gel, CH2Cl2–PE, 50:50–100:0), the de-
sired a-product (S)-43 (35.6 mg, 56%) as a colourless oil and the g-
product 44 (10.0 mg, 16%) as a colourless oil.
MS (NSI+): m/z (%) = 356 ([M + NH4]+, 100).
HRMS (NSI+): m/z [M + NH4]+ calcd for C20H19O4NF: 356.1293;
found: 356.1296.
Compound (S)-43
81% ee; chiral HPLC (Chiralpak AD-H, 5% i-PrOH–hexanes, flow
rate 1.0 mL min–1): tR = 12.3 (R), 16.3 min (S).
[a]D20 +125.8 (c 0.41, CHCl3).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
IR (thin film): 3084 (C–H), 1807 (C=O), 1768 (C=O), 1492 (C=C),
1278, 1188 (C–O), 980, 759, 688 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.92 (ABX, JAB = 13.9 Hz, JAX
=
Acknowledgment
7.9 Hz, 1 H, CHH), 3.05 (ABX, JBA = 13.9 Hz, JBX = 6.8 Hz, 1 H,
CHH), 5.20–5.22 (m, 1 H, =CHH), 5.28 (app. dd, J = 17.0, 1.4 Hz,
1 H, =CHH), 5.75–5.85 (m, 1 H, CH=CH2), 5.98 (s, 1 H, CH), 7.08–
7.10 (m, 2 H, HAr), 7.22–7.26 (m, 1 H, HAr), 7.35–7.39 (m, 2 H,
HAr), 7.43–7.46 (m, 3 H, HAr), 7.67–7.69 (m, 2 H, H2Ph, HAr).
The authors would like to thank the Royal Society for a University
Research Fellowship (ADS), the EPSRC (CJ), the Carnegie Trust
for the Universities of Scotland (LCM and CDC) and the EPSRC
National Mass Spectrometry Service Centre (Swansea).
13C NMR (100 MHz, CDCl3): d = 38.9, 60.5, 101.7, 121.0, 121.2,
125.4, 126.5, 127.6, 128.9, 129.6, 130.5, 130.6, 150.4, 154.8, 166.3,
173.0.
MS (ES+): m/z (%) = 338.1 (100, [M + NH4]+).
HRMS (ES+): m/z [M + NH4]+ calcd for C20H20O4N: 338.1387;
References and Notes
(1) For representative examples, see: (a) Figadére, B. Acc.
Chem. Res. 1995, 28, 359. (b) Tu, L.; Zhao, Y.; Yu, Z.;
Cong, Y.; Xu, G.; Peng, L.; Zhang, P.; Cheng, X.; Zhao, Q.
Helv. Chim. Acta 2008, 91, 1578. (c) de Guzman, F. S.;
Schmitz, F. J. J. Nat. Prod. 1990, 53, 926. (d) Evidente, A.;
Sparapano, L. J. Nat. Prod. 1994, 57, 1720. (e) Dogné, J.;
Supuran, C. T.; Pratico, D. J. Med. Chem. 2005, 48, 2251.
(f) Braña, M. F.; García, M. L.; Lòpez, B.; de Pascual-
Teresa, B.; Ramos, A.; Pozuelo, J. M.; Domínguez, M. T.
Org. Biomol. Chem. 2004, 2, 1864.
found: 338.1391.
Compound 44
16% ee; chiral HPLC (Chiralpak AD-H, 5% i-PrOH–hexanes, flow
rate 1.0 mL min–1): tR = 18.7 (1), 25.0 min (2).
[a]D20 +4.8 (c 0.48, CHCl3).
IR (thin film): 2977 (C–H), 1778 (C=O br), 1492 (C=C), 1213 (C–
O), 1185 (C–O), 1032, 734 cm–1.
(2) Singh, R. P.; Foxman, B. M.; Deng, L. J. Am. Chem. Soc.
2010, 132, 9558.
1H NMR (400 MHz, CDCl3): d = 3.08–3.19 (m, 2 H, CH2), 5.21 (t,
J = 1.3 Hz, 1 H, =CHH), 5.23–5.25 (m, 1 H, =CHH), 5.85–5.98 (m,
1 H, CH=CH2), 7.02–7.04 (m, 2 H, HAr), 7.22–7.26 (m, 1 H, HAr),
7.34–7.38 (m, 2 H, HAr), 7.43–7.48 (m, 3 H, HAr), 7.58 (t, J = 1.7
Hz, 1 H, CH), 7.59–7.62 (m, 2 H, HAr).
13C NMR (75 MHz, CDCl3): d = 29.7, 87.9, 118.7, 121.0, 125.9,
126.6, 129.2, 129.7, 129.7, 132.3, 133.8, 135.2, 146.8, 150.3, 166.0,
171.3.
(3) Brown, S. P.; Goodwin, N. C.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2003, 125, 1192.
(4) Shaw, S. A.; Aleman, P.; Christy, J.; Kampf, J. W.; Va, P.;
Vedejs, E. J. Am. Chem. Soc. 2006, 128, 925–934.
(5) For an excellent recent review of Lewis base mediated
reaction processes, see: Denmark, S. E.; Beutner, G. L.
Angew. Chem. Int. Ed. 2008, 47, 1560.
(6) For examples of our previous research programme
concerned with applications of NHCs in organocatalysis,
see: (a) Thomson, J. E.; Rix, K.; Smith, A. D. Org. Lett.
2006, 8, 3785. (b) Thomson, J. E.; Campbell, C. D.;
Concellón, C.; Duguet, N.; Rix, K.; Slawin, A. M. Z.; Smith,
A. D. J. Org. Chem. 2008, 73, 2784. (c) Campbell, C. D.;
Duguet, N.; Gallagher, K. A.; Thomson, J. E.; Lindsay, A.
G.; O’Donoghue, A.; Smith, A. D. Chem. Commun. 2008,
3528. (d) Duguet, N.; Campbell, C. D.; Slawin, A. M. Z.;
Smith, A. D. Org. Biomol. Chem. 2008, 6, 1108.
MS (ES+): m/z (%) = 338.1 (100, [M + NH4]+), 321.1 (16, [M +
H]+), 276.1 (77, [M – CO2]+).
HRMS (ES+): m/z [M + NH4]+ calcd for C20H20O4N: 338.1387;
found: 338.1386.
Phenyl (S)-3-Allyl-5-(4-fluorophenyl)-2-oxo-2,3-dihydrofuran-
3-carboxylate [(S)-45]
Following general procedure E using carbonate 31 (33.8 mg, 0.10
mmol) and chiral isothiourea 1 (3.08 mg, 0.01 mmol) in Et2O (0.3
mL) for 1 h gave, after chromatographic purification (CH2Cl2–PE,
50:50), 45 (21 mg, 62%) as a white solid; mp 26–28 °C; 76% ee;
(e) Thomson, J. E.; Kyle, A. F.; Concellón, C.; Gallagher, K.
A.; Lenden, P.; Morrill, L. C.; Miller, A. J.; Joannesse, C.;
Slawin, A. M. Z.; Smith, A. D. Synthesis 2008, 2805.
(f) Concellón, C.; Duguet, N.; Smith, A. D. Adv. Synth.
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York

PAPER
Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates
1879
Catal. 2009, 351, 3001. (g) Duguet, N.; Donaldson, A.;
Campbell, C. D.; Johnston, C. P.; Duguet, N.; Concellón, C.;
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Leckie, S. M.; Douglas, J.; Shapland, P.; Churchill, G.;
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Shapland, P.; Slawin, A. M. Z.; Smith, A. D. Tetrahedron:
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Concellón, C.; Churchill, G.; Slawin, A. M. Z.; Smith, A. D.
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(7) For examples of our previous research programme
concerned with applications of isothioureas in
organocatalysis, see: (a) Joannesse, C.; Simal, C.;
Concellón, C.; Thomson, J. E.; Campbell, C. D.; Slawin, A.
M. Z.; Smith, A. D. Org. Biomol. Chem. 2008, 6, 2900.
(b) Woods, P. A.; Morrill, L. C.; Lebl, T.; Slawin, A. M. Z.;
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(c) Belmessieri, D.; Joannesse, C.; Woods, P. A.;
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Duguet, N.; Concellón, C.; Bragg, R. A.; Smith, A. D. Org.
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(11) 2 was readily prepared on a multigram scale by alkylation of
the dianion of phenylacetic acid with 2-methyloxirane; see
experimental section for synthesis.
(12) The selenation/elimination sequence was based upon
literature precedent in these systems: Pour, M.; Spulák, M.;
Balsánek, V.; Kunes, J.; Kubanová, P.; Buchta, V. Bioorg.
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(14) Reaction in toluene and Et2O at –20 °C gave <10%
conversion to C-carboxy products, that was assumed to be
due to low solubility of 1 at these temperatures.
(15) (R)-TADMAP was kindly donated by Prof. Edwin Vedejs.
Consistent with the literature, rearrangement of furanyl
carbonate 5 with (R)-TADMAP gave a 60:40 mixture of a/g
regioisomers, with purification giving the major a-regio-
isomer 8 in 49% yield and 85% ee.
(16) For representative examples that demonstrate the preference
of substituents adjacent to an N-acyl group in heterocyclic
compounds to adopt a pseudoaxial position, see:
(a) Sinclair, P. J.; Zhai, D.; Reibenspies, J.; Williams, R. M.
J. J. Am. Chem. Soc. 1986, 108, 1103. (b) Dellaria, J. F.;
Santarsiero, B. D. J. Org. Chem. 1989, 54, 3916. (c) Drew,
M. G. B.; Harwood, L. M.; Park, G.; Price, D. W.; Tyler, S.
N. G.; Park, C. R.; Cho, S. G. Tetrahedron 2001, 57, 5641.
(17) Anderson, R. J.; Adams, K. G.; Chinn, H. R.; Henrick, C. A.
J. Org. Chem. 1980, 45, 2229.
(8) For initial work, see: (a) Steglich, W.; Höfle, G.
Tetrahedron Lett. 1970, 11, 4727. For asymmetric Steglich
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C.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 11532.
(c) Shaw, S. A.; Aleman, P.; Vedejs, E. J. Am. Chem. Soc.
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Richards, C. J. Org. Lett. 2006, 8, 769. (e) Busto, E.; Gotor-
Fernández, V.; Gotor, V. Adv. Synth. Catal. 2006, 348,
2626. (f) Seitzberg, J. G.; Dissing, C.; Søtofte, I.; Norrby, P.-
O.; Johannsen, M. J. Org. Chem. 2005, 70, 8332. (g) Dietz,
F. R.; Gröger, H. Synlett 2008, 663. (h) Dietz, F. R.; Gröger,
H. Synthesis 2009, 4208. (i) Uraguchi, D.; Koshimoto, K.;
Miyake, S.; Ooi, T. Angew. Chem. Int. Ed. 2010, 49, 5567.
(j) Zhang, Z.; Xie, F.; Jia, J.; Zhang, W. J. Am. Chem. Soc.
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(9) Joannesse, C.; Johnston, C. P.; Concellón, C.; Simal, C.;
Philp, D.; Smith, A. D. Angew. Chem. Int. Ed. 2009, 48,
8914.
(10) Selected alternative applications of chiral isothioureas in
asymmetric catalysis are listed herein. For kinetic
resolutions using anhydrides as acylating agents, see:
(a) Birman, V. B.; Jiang, H.; Li, X.; Geo, V.; Uffman, E. W.
J. Am. Chem. Soc. 2006, 128, 6536. (b) Birman, V. B.; Li,
X. Org. Lett. 2006, 8, 1351. (c) Birman, V. B.; Geo, L. Org.
Lett. 2006, 8, 4859. (d) Birman, V. B.; Jiang, H.; Li, X. Org.
Lett. 2007, 9, 3237. (e) Birman, V. B.; Li, X. Org. Lett.
2008, 10, 1115. (f) Yang, X.; Birman, V. B. Adv. Synth.
Catal. 2009, 351, 2525. (g) Xu, Q.; Zhou, H.; Geng, X.;
Chen, P. Tetrahedron 2009, 65, 2232. (h) Belmessieri, D.;
Joannesse, C.; Woods, P. A.; MacGregor, C.; Jones, C.;
Synthesis 2011, No. 12, 1865–1879 © Thieme Stuttgart · New York