Preparation and utility of cyclic enol carbonates

Article abstract of DOI:10.1055/s-2004-822401

Treatment of iodo carbonates with LiHMDS at low temperature readily affords cyclic enol carbonates with either five- or six-membered rings. Reaction with potassium fert-butoxide results in the in situ formation of an enolate which after transmetallation p

Full text of DOI:10.1055/s-2004-822401

PAPER
1399
Preparation and Utility of Cyclic Enol Carbonates
Preparationand
U
tility
a
of Cyclic
E
t
nol Ca
t
rbona
t
h
es ew L. Maddess, Mark Lautens*
Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Davenport Research, Toronto, Ontario, M5S 3H6,
Canada
Fax +1(416)9468185; E-mail: mlautens@alchemy.chem.utoronto.ca
Received 15 April 2004
This article is dedicated to Professor Mukaiyama on the occasion of his 77th birthday.
There have been two previous reports of routes that afford
Abstract: Treatment of iodo carbonates with LiHMDS at low tem-
products of type 2. The first by Marshall8 utilizes an io-
perature readily affords cyclic enol carbonates with either five- or
dolactonization reaction of homopropargylic alcohols fol-
six-membered rings. Reaction with potassium tert-butoxide results
in the in situ formation of an enolate which after transmetallation
lowed by reduction with tributyl tin hydride. Heathcock’s9
participates in aldol or Mannich reactions. Alternatively, the potas- approach employs a conjugate reduction of a b-phenyl
carbonate enone using Stryker’s reagent.10 In both cases
sium enolates can be trapped with silylating or triflating agents. The
regio- and stereoselective generation of silyl enol ethers with up to
four substituents can be achieved.
the substrate scope is not well established and the reagents
involved are toxic or expensive. It is known that the six-
Key words: enols, aldol reactions, tandem reactions, stereoselec-
membered cyclic enol carbonates 2 are precursors to b-
tivity, regioselectivity
hydroxy ketones, b-keto carbonates, and a¢,b-hydroxy ke-
tones.8,9
Addition of an appropriately chosen metal nucleophile to
Iodocarbonate cyclization on an allylic,1 or particularly a
2 might allow for the in situ generation of an enolate
homoallylic p-system,1,2 is a well established and valuable
(Scheme 1) that then could be trapped or participate in al-
synthetic operation. First described by Cardillo in 1981, a
dol or Michael reactions. If the cyclic enol carbonates 2
number of conditions1,2 now exist to effect this transfor-
contained geometrically defined substituents on the alkyl-
mation with various levels of diastereoselectivity. Smith’s
idene terminus, it should be possible to generate enolates
IBr protocol2b generally provides the highest ratio of syn
in a regio- and stereoselective fashion. This report sum-
to anti products 1. The resulting iodo carbonates 1 are ver-
marizes our efforts to achieve these objectives.
satile intermediates providing facile access to a wide vari-
ety of structural motifs,1b,2 including epoxy alcohols,
diols, triols, and cyclic carbonates. One area of investiga-
tion that has received scant attention is a base-induced de-
hydrohalogenation to form various cyclic enol carbonates
2 (Scheme 1).
The study was initiated on the iodo carbonate derived
from benzaldehyde 4. In general, all additional substrates
were prepared following the sequence shown in
Scheme 2,11 wherein an aldehyde was allylated and then
protected in situ when possible12 as the tert-butyl carbon-
ate with Boc2O. Most often, the iodine-induced electro-
philic cyclization was performed utilizing Smith’s
conditions2b to simplify isolation and characterization.
However, since IBr is incompatible with polyolefinic sub-
strates,2b the milder I2–MeCN system of Bartlett2a was
used in some cases.
O
O
O
Nuc
O
OM
O
O
O
O
Nuc
Base
I
R
R
R
1
3
2
Scheme 1 Strategy for the preparation of cyclic enol carbonates and
use as an enolate equivalent
Alkylidene products are known when the ring size is five
and are typically prepared by condensation of a propargyl-
ic alcohol with carbon dioxide in the presence of a cata-
lyst.3 Subsequent work has demonstrated that these
compounds are useful synthetic intermediates for the
preparation a wide variety of compounds such as oxazoli-
dinones, b-oxopropyl carbonates and carbamates, fura-
none derivatives and other heterocycles, cyclopropanes,
optically active bicyclic carbonates and 1,2-diols.4–7
Scheme 2 General approach to the synthesis of iodo carbonate star-
ting materials
With multi-gram quantities of 4 readily available we be-
gan optimization of the desired elimination reaction
(Table 1). A number of amine bases (Et3N, DBU, and
Hunig’s Base) and inorganic bases (NaH, KH, CsCO3,
and K2CO3) were either ineffective or did not provide the
desired product 5 in good yield. For example DBU slowly
converted the starting material to product 5 (Table 1, en-
tries 1 and 2) but upon prolonged stirring only the unde-
SYNTHESIS 2004, No. 9, pp 1399–1408
x
x
.
x
x
.2
0
0
4
Advanced online publication: 08.06.2004
DOI: 10.1055/s-2004-822401; Art ID: C12804SS
© Georg Thieme Verlag Stuttgart · New York

1400
M. L. Maddess, M. Lautens
PAPER
sired double elimination product 6 was observed. In hydrohalogenation creating 1,3-allylic strain in the transi-
contrast LiHMDS (Table 1, entry 4) afforded the desired tion state to products. Both syn and anti iodo carbonates
cyclic enol carbonate 5 in very high yield with little or no behaved similarly, affording the same product in similar
elimination products. Changing to the corresponding so- yield and reaction time (Table 2, entries 1 and 6). Thus the
dium or potassium bis(trimethylsilyl) amides (Table 1, selectivity in the iodo carbonate cyclization protocols is
entries 5 and 6), and other strong bases such as LDA or not of significant concern. Finally we tested the approach
potassium tert-butoxide was less effective. Further opti- developed for the synthesis of the six-membered family of
mization of the reaction indicated that THF was the sol- enol carbonates on a five-membered analogue (Table 2,
vent of choice. As the temperature was raised, or the
amount of base increased, the amount of product was
markedly reduced. It appears that LiHMDS at this temper-
ature combines the necessary basicity with low nucleophi-
licity to avoid undesired side reactions.
Table 2 Substrate Scope for Preparation of Cyclic Enol Carbonatesa
O
1) LiHMDS 1.2 equiv
THF, –78 o
O
C
O
O
O
O
20 min to 3 h
R3
I
R
R
2) aq NH4Cl –78 oC to r.t.
R2 R3
R2
Table 1 Effect of the Basea
Entry Substrate
No.
Product, yield (%)b
O
O
O
Base 1.2 equiv
THF
O
O
O
O
1
4
5, 91
O
+
I
(89c)
O
O
O
O
I
I
4
6
Ph
Ph
5
2
3
4
O
O
O
7
8
9
17, 96
18, 33
Entry Base
Temp (°C) Time (h) Yield of 5 (%)b
1
2
3
4
5
6
7
DBU
DBU
LDA
20
20
1
20
1
25
0
O
O
O
O
–78
–78
–78
–78
–78
10
I
Ph
Ph
LiHMDS
1
94 (91c)
19, 87
E(O):Z(O) 30:1d
NaHMDS
KHMDS
KOt-Bu
1
62
43
0
1
I
5
6
O
10
11
20, 92
1
Z(O):E(O) 30:1d
O
O
O
a All reactions performed on a 0.46 mmol scale.
b HPLC yield.
Ph
Ph
I
c Isolated yield.
21, 80
O
(87c)
O
I
A series of iodo carbonates was then prepared to test the
generality of this approach to various cylic enol carbon-
ates. These results are collected in Table 2. The previous-
ly optimized conditions performed well for nearly all
types of substrates tested, be they aromatic (Table 2, en-
tries 1 to 5), conjugated (Table 2, entry 6), or aliphatic
(Table 2, entries 7 to 11). One exception relates to a sub-
strate derived from a syn crotylation of benzaldehyde
(Table 2, entry 3). The exceptionally slow rate and low
yield of this reaction is consistent with an expected E2 de-
7
8
12
13
22, 56
O
(69e)
O
O
I
O
23, 91
O
O
I
Cy
9
10
11
14
15
16f
24, 93
25, 99
26, 82
I
O
O
O
TBDPSO
I
Protocol A
O
O
O
1) KOtBu 1.2 equiv (add over 10 s)
O
THF, –78 oC, 10 s
BocO
O
O
O
O
2) aq NH4Cl
O
O
97%
5
27
I
Protocol B
1) ZnCl2 1.1 equiv then
KOtBu 2.4 equiv
THF, –95 oC, 5 min
O
a All reactions performed on 0.1 to 1.0 mmol scale.
b Isolated yields.
BocO
O
O
O
c Anti analogue of substrate.
d Determined by 1H NMR.
e 30 mmol scale.
2) aq NH4Cl
97%
5
27
Scheme 3 Formation of b-keto carbonates
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York
f Syn to anti 2.2:1.0.

PAPER
Preparation and Utility of Cyclic Enol Carbonates
1401
Table 3 Effect of Additives on in situ Aldol Reactionsa
O
1) KOtBu 1.2 equiv (add over 10 s)
O
O
BocO
O
OH
THF, –78 oC, 10 s
2) Additive 1.2 equiv (add over 10 s)
5 min
3) PhCHO, 4 h
28
5
Entry
Additive
–
Yield (%)a
drb
1
2
3
4
5
6
7
8
0
–
ZnCl2
83 (81c)
20
2.2:1
1:1
MgBr2·OEt2
TiCl4
29
1:1.2
6.7:1
3.2:1
1.5:1
1.2:1
Bu2BOTf
Cy2BCl
9-BBNOTf
Cp2ZrCl2
83d
69d
72d
48
a Reactions performed on a 0.46 mmol scale.
b Determined by 1H NMR.
c Isolated yield.
d Oxidative work up [30% H2O2– NaOH (1 M)–Et2O).
entry 111b) and were pleased to see that the reaction con- suggesting that the potassium enolate–alkoxide was too
ditions worked equally well. This approach affords anoth- basic a species. Consequently we investigated the reactiv-
er route to this useful class of molecules.
ity of several metal enolates prepared by the addition of
various metal salts (Table 3, entries 1 to 8).
Attention was then focused on finding a suitable nucleo-
phile for the in situ preparation of the enolates. Extensive The most useful additive we have identified to date is zinc
screening and optimization resulted in the two sets of con- chloride (Table 3, entry 2) which gave very high yields
ditions shown in Scheme 3.
(80 to 95%) for all classes of aldehydes (aromatic, conju-
gated, and aliphatic) and imines tested, although it exhib-
ited relatively poor diastereoselectivity (1:1 to 3:1).13 In
Initially potassium tert-butoxide did not appear to be a
good candidate to effect this transformation; however this
was in large part due to the rate of addition of the base
which is quite important as the reaction is extremely rapid
(Scheme 3, protocol A). With very short reaction times,
27 was formed in excellent yields (Scheme 3, protocol A).
Quenching studies at increasing reaction times indicated
that the stability of the enolate was low as widely differing
amounts of 27 were observed. The addition of ZnCl2 prior
to the base improved the consistency of the reaction, pre-
sumably by mitigating the enolate basicity and the rate of
addition was no longer an issue (Scheme 3, protocol B). In
this case more t-BuOK must be added as some of this re-
agent is consumed by reacting with ZnCl2. For most pur-
poses the simple protocol that lacks this latter reagent is
preferred, provided quenching or further reaction is rapid.
The lithium and sodium analogues were far less effective
as were any other solvents except THF. Finally increases
in temperature resulted in a serious decrease in the yield.
Table 4 Formation of Vinyl Triflatesa
O
1) KOtBu 1.2 equiv (add over 10 s)
BocO
R
OTf
n
O
O
n
THF, –78 oC, 10 s
R
2) (CF3SO2)2NC6H5 1.4 equiv
90 min
R2
R2
n = 0, 1
n = 0, 1
Entry
1
Substrate
No.
Product, yield (%)b
O
5
29, 99
O
O
Ph
2
3
O
22
17
30, 97
31, 82
O
O
O
O
O
Ph
Quenching the reaction of 4-methylene-6-phenyl[1,3]di-
oxan-2-one (5) and t-BuOK shortly after the addition of
the base resulted in nearly full deuterium incorporation.
Attempts to trap the potassium enolate with various alde-
hydes in an aldol reaction failed to yield any of the expect-
ed addition product. However we did observe some aldol
product that had eliminated the Boc-protected carbinol,
O
4
26
32, 94
O
O
a All reactions performed on a 0.50 mmol scale.
b Isolated yields.
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

1402
M. L. Maddess, M. Lautens
PAPER
some cases the diastereoselectivity can be improved by edge, very few methods19–21 exist to prepare such com-
use of Bu2BOTf (Table 3, entry 5); however this is not a pounds especially in an acyclic system.
general effect.13
In summary, treatment of iodo carbonates with LiHMDS
Upon addition of a solution of N-phenyltrifluoromethane at low temperature affords cyclic enol carbonates with ei-
sulfonamide14 to the potassium enolate, vinyl triflates ther five- or six-membered-ring sizes in good to excellent
were isolated in excellent yields (Table 4, entries 1 to 4). yields. Reagents involved in their preparation are inex-
Alternatively the addition of TBSOTf yielded silyl enol pensive, and the reactions are easy to perform while the
ethers that were easily purified using conventional tech- products are stable and often solids. Ready access to such
niques.15 These results are collected in Table 5.
compounds will allow for the development of some useful
chemistry to prepare a variety of other structural motifs, as
has already been demonstrated in the five-membered-ring
series. For example, we have demonstrated that reaction
with potassium tert-butoxide results in the in situ forma-
tion of enolates which after transmetallation participate in
aldol or Mannich reactions. Alternatively, the potassium
enolates may be trapped with silylating or triflating
agents. In most cases this allows the regio- and stereose-
lective generation of silyl enol ethers with up to four sub-
stituents which is difficult to accomplish by other means.
In general this transformation was very efficient (Table 5,
entries 1 to 9) for all substrates tested. Of particular inter-
est was whether the stereochemical information in config-
urationally defined cyclic enol carbonates would be
maintained on conversion to the silyl enol ether.16 To this
end we prepared a number of such compounds (19, 20,
33–35) using methodology discussed above or via other
literature protocols (33,17 34 and 3518).
Subjecting the cyclic enol carbonates 19, 20, 33–35
(Table 5, entries 6 to 9) to the stated reaction conditions in
most cases yielded products 41–44 in which the stereo-
chemical information present in the starting materials was
maintained. The same was not true for the E(O)-cylic enol
enolate 19, where a mixture of isomers was observed (40).
It seems plausible that the metal–oxygen ion pair under
these conditions is not sufficiently tight to prevent enolate
isomerization. The products 43 and 44, based upon tetra-
substituted cyclic enol carbonates 34 and 35 are the equiv-
The following includes representative experimental procedures and
details for isolation of compounds. All reported preparations of sub-
strates are unoptimized. Full characterisation of all novel, and par-
tial characterisation of known, compounds presented in the report
are described.
1H NMR were recorded using Varian instruments at 300, 400 or 500
MHz. 13C NMR were recorded using Varian instruments at 75, 100,
or 125 MHz. 13F NMR were recorded using Varian instruments at
alent of the regio- and stereoselective synthesis of a silyl 282, or 376 MHz. NMR shifts are reported relative to a TMS inter-
nal standard or relative to BF3·OEt2 for 19F. IR spectra were ob-
tained using a Perkin–Elmer FT-IR spectrometer (spectrum 1000).
enol ether of an a,a¢-disubstituted ketone. To our knowl-
Table 5 Substrate Scope for Conversion to Silyl Enol Ethersa
O
1) KOtBu 1.2 equiv (add over 10 s)
BocO
R
OTBS
O
O
THF, –78 oC, 10 s
R3
R3
R
n
n
R2 R4
2) TBSOTf 1.4 equiv
90 min
R2 R4
n = 0, 1
n = 0, 1
Entry Substrate
No.
Product, yield (%)b Entry Substrate
No.
Product, yield (%)b
1
5
36, 81
37, 80
38, 93
6
7
8
O
20
41, 74
O
Z(O):E(O) 30:1c
Z(O):E(O) 30:1c
O
O
O
O
O
O
O
Ph
Ph
Ph
2
3
21
22
33
42, 93
O
O
Z(O):E(O) 30:1c
Z(O):E(O) 30:1c
O
Ph
Ph
34
43, 99
O
O
E(O):Z(O) 30:1c
E(O):Z(O) 30:1c
O
O
O
O
O
4
5
O
26
39, 96
40, 93
9
35
44, 97
O
Z(O):E(O) 30:1c
Z(O):E(O) 30:1c
O
O
O
Ph
O
19
E(O):Z(O) 30:1b E(O):Z(O) 4.2:1c
O
O
Ph
a All reactions performed on a 0.1 to 1.0 mmol scale.
b Isolated yields.
c Determined by 1H NMR.
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

PAPER
Preparation and Utility of Cyclic Enol Carbonates
1403
HRMS were obtained on a VG 70-250S (double focusing) mass
spectrometer at 70 eV or an ABI/Sciex Qstar mass spectrometer
with an ESI source, MS/MS and accurate mass capabilities. HPLC
analysis was performed using a Hewlett Packard Series 1100 HPLC
with a UV detector. Mps were determined using a Fisher–Johns mp
apparatus and are uncorrected.
(5S*,6S*)-5-Methyl-4-methylene-6-phenyl[1,3]dioxan-2-one
(18)
A 25 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. To this was added 8 (750 mg, 2.26
mmol) and freshly distilled THF (10 mL). The mixture was cooled
to –78 °C and LiHMDS (2.71 mL, 2.71 mmol) was added dropwise.
After the typical reaction time of 1 h, very poor conversion was not-
ed by TLC; thus an additional equivalent of LiHMDS was added
and the reaction left an additional 5 h, but little progress was noted.
An approximately equal volume of aq NH4Cl was added via syringe
and the mixture allowed to warm to r.t. where it was then transferred
to a separating funnel with Et2O and additional aq NH4Cl. The or-
ganic layer was isolated and the aq phase extracted a second time
with Et2O. The combined organics were dried (MgSO4), filtered,
and concentrated in vacuo. Attempts were made to purify the prod-
uct by flash chromatography; however, separation of the product
from the remaining starting material was not possible. Freshly dis-
tilled THF was added to the crude reaction mixture, the resulting so-
lution recooled to –78 °C, and KHMDS (0.75 equiv) was added via
syringe. This resulted in consumption of the starting material al-
though it did not seem to afford additional product. The reaction
was quenched and worked up as noted above and the resulting crude
reaction mixture purified by flash chromatography (10 to 17%
EtOAc–hexanes) to afford the product.
THF, dioxane, and Et2O were distilled from sodium–benzophe-
none. Pentane, toluene, CH2Cl2, and MeCN were distilled from cal-
cium hydride or used as ACS reagents if noted. LiHMDS (1 M,
THF), t-BuOK (1 M, THF), ZnCl2 (1 M, Et2O), and Bu2BOTf (1 M,
CH2Cl2) were purchased from Aldrich as solutions and used as re-
ceived. AllylMgBr was purchased from Aldrich as a solution (1.0
M) in Et2O, and was titrated periodically. IBr, I2 and various other
starting materials were purchased from Aldrichand were used as re-
ceived without further purification. Instances of aq NH4Cl and
NaHCO3 refer to sat. aq solutions. All reactions were performed un-
der an atmosphere of nitrogen in flame dried glassware using stan-
dard syringe–septum techniques unless otherwise noted.11
LiHMDS Dehydrohalogenations; ( )-4-Methylene-6-phe-
nyl[1,3]dioxan-2-one (5); General Procedure
A 100 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. It was then charged with 4 (750
mg, 2.36 mmol) and freshly distilled THF (ca. 1 M; 25 mL). The re-
sulting solution was cooled to –78 °C and LiHMDS (1 M; 2.83 mL,
2.83 mmol) was added dropwise. The reaction was left stirring for
1 h, then aq NH4Cl was added via syringe and the mixture allowed
to warm to r.t. where it was then transferred to a separating funnel
with Et2O and additional aq NH4Cl. The organic layer was isolated
and the aq phase extracted a second time with Et2O. The combined
organics were dried (MgSO4), filtered, and concentrated in vacuo.
The crude reaction mixture was purified by flash chromatography
(17% EtOAc–hexanes) to afford the desired product.
Yield: 33%; viscous light yellow oil; Rf = 0.23 (17% EtOAc–hex-
anes).
IR (neat): 2980, 1767, 1670, 1455, 1279, 1202, 1076, 699 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.43–7.35 (m, 3 H), 7.29–7.26 (m,
2 H), 5.54 (d, J = 3.6 Hz, 1 H), 4.86–4.84 (m, 1 H), 4.40–4.38 (m, 1
H), 3.08–3.01 (m, 1 H), 0.97 (d, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 155.5, 146.2, 134.7, 128.8, 128.7,
125.9, 93.8, 81.6, 35.2, 11.7.
Yield: 91%; white solid; Rf = 0.18 (17% EtOAc–hexanes);
mp 81 °C.
HRMS: m/z calcd for C12H13O3: 205.0865; found: 205.0863.
( )-(4E)-4-Ethylidene-6-phenyl[1,3]dioxan-2-one (19)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 9 (230 mg, 1.0 mmol). The product was
purified by flash chromatography (17% EtOAc–hexanes) and was
recovered as an oil.
Yield: 87% (single olefin isomer to the detection levels of 1H
NMR); colorless oil; Rf = 0.40 (25% EtOAc–hexanes).
IR (thin film, CH2Cl2): 3037, 1769, 1673, 1456, 1349, 1282, 1074,
759 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.46–7.34 (m, 5 H), 5.44 (dd,
J = 10.8, 3.6 Hz, 1 H), 4.87–4.85 (m, 1 H), 4.43–4.42 (m, 1 H), 2.94
(dd, J = 15.2, 3.2 Hz, 1 H), 2.80 (ddd, J = 15.2, 10.8, 1.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 150.5, 146.4, 136.5, 129.3, 129.0,
125.7, 94.8, 78.8, 33.3.
IR (neat): 3037, 2925, 1769, 1697, 1455, 1232, 1067, 759 cm–1.
HRMS (electrospray): m/z calcd for C11H10O3Na: 213.0527; found:
213.0521.
1H NMR (400 MHz, CDCl3): d = 7.45–7.36 (m, 5 H), 5.42–5.36 (m,
2 H), 3.05 (dd, J = 15.6, 3.2 Hz, 1 H), 2.73–2.64 (m, 1 H), 1.61 (dd,
J = 7.2, 1.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 147.0, 144.2, 136.9, 129.2, 128.9,
125.8, 105.1, 78.4, 29.2, 10.6.
(5R*,6S*)-5-Methyl-4-methylene-6-phenyl[1,3]dioxan-2-one
(17)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 7 (1.85 g, 5.8 mmol). The product was pu-
rified by flash chromatography (17% EtOAc–hexanes) and was
recovered as an oil.
HRMS (electrospray): m/z calcd for C12H12O3Na: 227.0678; found:
227.0682.
Yield: 96%; colorless oil; Rf = 0.23 (17% EtOAc–hexanes).
( )-(4Z)-4-Ethylidene-6-phenyl[1,3]dioxan-2-one (20)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 10 (125 mg, 0.38 mmol). The product was
purified by flash chromatography (17% EtOAc–hexanes) and was
recovered as an oil.
Yield: 92% (single olefin isomer to the detection levels of 1H
NMR); colorless oil; Rf = 0.43 (25% EtOAc–hexanes).
IR (neat): 2983, 1769, 1667, 1457, 1346, 1262, 1179, 1073, 866,
763, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.47–7.42 (m, 3 H), 7.37–7.34 (m,
2 H), 5.10 (d, J = 10.0 Hz, 1 H), 4.91 (m, 1 H), 4.50 (m, 1 H), 2.86–
2.76 (m, 1 H), 1.62 (d, J = 13.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 156.1, 146.3, 135.6, 129.6, 128.9,
127.0, 93.3, 84.7, 36.2, 12.6.
IR (neat): 2922, 1767, 1709, 1454, 1350, 1244, 1172, 1072, 760
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.44–7.33 (m, 5 H), 5.41 (dd,
J = 10.4, 3.2 Hz, 1 H), 4.76 (qd, J = 7.2, 1.6 Hz, 1 H), 2.84 (dd,
HRMS (electrospray): m/z calcd for C12H12O3Na: 227.0678; found:
227.0689.
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

1404
M. L. Maddess, M. Lautens
PAPER
J = 15.2, 3.6 Hz, 1 H), 2.78–2.73 (m, 1 H), 1.72 (dd, J = 7.2, 1.6
HRMS (electrospray): m/z calcd for C14H16O3: 232.1100; found:
Hz, 3 H).
232.1085.
13C NMR (100 MHz, CDCl3): d = 146.9, 143.5, 136.9, 129.2, 128.9,
( )-4-(2-{[tert-Butyl(diphenyl)silyl]oxy}ethyl)-6-methyl-
ene[1,3]dioxan-2-one (25)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 15 (2.67 g, 5.1 mmol). The product was
purified by flash chromatography (10% EtOAc–hexanes) and was
recovered as an oil.
125.7, 79.4, 33.7, 9.5.
HRMS (electrospray): m/z calcd for C12H12O3Na: 227.0678; found:
227.0681.
( )-4-Methylene-(6E)-styryl[1,3]dioxan-2-one (21)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 11 (360 mg, 1.05 mmol). The product was
purified by flash chromatography (17% to 25% EtOAc–hexanes)
and was recovered as a solid.
Yield: 99%; colorless oil; Rf = 0.17 (17% EtOAc–hexanes).
IR (neat): 2930, 1776, 1673, 1171, 1109, 703 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.67–7.62 (m, 4 H), 7.46–7.36 (m,
6 H), 4.80–4.72 (m, 1 H), 4.72–4.63 (m, 1 H), 4.35–4.33 (m, 1 H),
3.88 (ddd, J = 10.8, 8.4, 4.5 Hz, 1 H), 3.76 (ddd, J = 10.8, 5.4, 5.4
Hz, 1 H), 2.73 (dd, J = 15.3, 3.3 Hz, 1 H), 2.52–2.42 (m, 1 H), 2.05–
1.92 (m, 1 H), 1.90–1.78 (m, 1 H), 1.05 (s, 9 H).
Yield: 80%; white solid; Rf = 0.37 (25% EtOAc–hexanes);
mp 102 °C.
IR (neat): 2922, 1763, 1672, 1348, 1279, 1215, 1176, 1076, 974,
872, 752 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.41–7.29 (m, 5 H), 6.76 (d,
J = 16.0 Hz, 1 H), 6.17 (dd, J = 16.0, 6.8 Hz, 1 H), 5.11–5.05 (m, 1
H), 4.86 (s, 1 H), 4.43 (s, 1 H), 2.88 (dd, J = 15.0, 3.2 Hz, 1 H), 2.68
(dd, J = 15.0, 8.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 150.7, 146.4, 135.5, 133.2, 133.1,
129.9, 127.8, 94.4, 75.3, 59.0, 37.1, 31.0, 26.9, 19.2.
HRMS: m/z calcd for C19H19O4Si: 339.1053; found: 339.1048.
( )-4-Methyl-5-methylene-4-(4-methylpent-3-enyl)[1,3]diox-
olan-2-one (26)22
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 16 (324 mg, 1.0 mmol) and an extended
reaction time of 2 h. The product was purified by flash chromatog-
raphy (5% EtOAc–hexanes) and was recovered as an oil.
13C NMR (100 MHz, CDCl3): d = 150.2, 146.1, 135.2, 135.0, 128.9,
128.8, 126.9, 123.5, 95.0, 77.8, 31.6.
HRMS (electrospray): m/z calcd for C13H12O3Na: 239.0684; found:
239.1636.
(6R*)-4-Methyl-6-methylene[1,3]dioxan-2-one (22)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 12 (110 mg, 0.43 mmol). The product was
purified by flash chromatography (50% pentane–Et2O) and was re-
covered as an oil.
Yield: 82%; colorless oil; Rf = 0.46 (17% EtOAc–hexanes).
( )-(4Z)-4-Benzylidene-6-phenyl[1,3]dioxan-2-one (33)17
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. To this was added 5 (190.2 mg, 1.0
mmol), dioxane (3 mL), PPh3 (26 mg, 0.1 mmol), CF3CO2Ag (243
mg, 1.1 mmol), iodobenzene (123 mL, 1.1 mmol) and finally
Pd(OAc)2 (22 mg, 0.1 mmol). The reaction mixture was heated to
100 °C and left for 20 h and then the flask was allowed to cool to r.t.
Approximately an equal volume of aq NH4Cl was added and the
contents transferred to a separating funnel with CH2Cl2. The organic
layer was isolated, the aq layer back extracted with CH2Cl2 and the
combined organics were dried (MgSO4), filtered and concentrated
in vacuo. The crude residue was analyzed by 1H NMR (300 MHz,
CDCl3), which indicated a ratio of olefin isomers Z–E = 3.5:1, with
diagnostic signals d = 6.54 (E, d, J = 2.1 Hz, 0.25 H), 5.56 (Z, s,
1.07 H), 5.52 (Z, dd, J = 9.2, 4.8 Hz, 1 H), 5.43 (E, d, J = 10.9, 0.29
Hz). The crude reaction mixture was purified by flash chromatogra-
phy (17% EtOAc–hexanes) to yield a white solid; the product being
a mixture of olefin isomers (yield 56%). The purified material was
taken up in a minimum of hot EtOAc and Et2O was added as a non-
solvent. Slow evaporation afforded crystals. The mother liquor was
removed, the residual solid rinsed with a small amount of Et2O to
afford 33 as a single olefin isomer by 1H NMR.
Yield: 56%; colorless oil; Rf = 0.34 (50% pentane–Et2O).
IR (neat): 2987, 1769, 1674, 1354, 1284, 1227, 1136, 1070 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.81–4.79 (m, 1 H), 4.59 (qdd,
J = 9.6, 6.4, 3.6 Hz, 1 H), 4.38 (m, 1 H), 2.73 (dd, J = 15.2, 3.6 Hz,
1 H), 2.45 (ddd, J = 15.2, 9.6, 1.6 Hz, 1 H), 1.45 (d, J = 6.4 Hz, 3
H).
13C NMR (100 MHz, CDCl3): d = 150.1, 146.5, 94.5, 74.3, 32.4,
20.2.
HRMS (electrospray): m/z calcd for C6H9O3: 129.0546; found:
129.0540.
(4R*,5R*)-4-Cyclohexyl-5-methyl-6-methylene[1,3]dioxan-2-
one (23)8
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 13 (137 mg, 0.41 mmol). The product was
purified by flash chromatography (10% EtOAc–hexanes) and was
recovered as an oil.
Yield: 91%; colorless oil; Rf = 0.38 (17% EtOAc–hexanes).
Yield 17%; Rf = 0.18 (17% EtOAc–hexanes); mp 134 °C.
( )-4-Methylene-6-(3-phenylpropyl)[1,3]dioxan-2-one (24)
Prepared according to the general protocol outlined for the prepara-
tion of compound 5 with 14 (750 mg, 2.1 mmol). The product was
purified by flash chromatography (17 to 25% EtOAc–hexanes) and
was recovered as an oil.
IR (thin film, CHCl3): 3051, 2915, 1768, 1681, 1242, 1203, 1163,
694 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.65–7.62 (m, 2 H), 7.45–7.33 (m,
6 H), 7.28–7.23 (m, 1 H), 5.58 (s, 1 H), 5.52 (dd, J = 9.2, 4.8 Hz, 1
H), 3.00–2.90 (m, 2 H).
Yield: 93%; colorless oil; Rf = 0.41 (33% EtOAc–hexanes).
IR (neat): 2927, 1773, 1673, 1365, 1282, 1172, 1073 cm–1.
13C NMR (100 MHz, CDCl3): d = 146.0, 143.1, 136.5, 132.7, 129.4,
129.2, 129.0, 128.6, 127.7, 125.8, 109.8, 79.4, 34.6.
1H NMR (300 MHz, CDCl3): d = 7.32–7.27 (m, 2 H), 7.23–7.14 (m,
3 H), 4.79–4.77 (m, 1 H), 4.45–4.36 (m, 1 H), 4.35–4.33 (m, 1 H),
2.71–2.61 (m, 3 H), 2.48–2.39 (m, 1 H), 1.94–1.60 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 150.6, 146.6, 141.3, 128.5, 128.4,
126.2, 94.5, 77.8, 35.3, 33.8, 30.9, 26.3.
HRMS: m/z calcd for C17H14O3: 266.0943; found: 266.0935.
(4Z)-4-(1-Phenylbut-3-enylidene)[1,3]dioxolan-2-one (34)18
A 250 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. To this was added 2-butyn-1-ol
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

PAPER
Preparation and Utility of Cyclic Enol Carbonates
1405
(2.26 mL, 30 mmol) and THF (30 mL). The resulting solution was
cooled to 0 °C and BuLi (18.2 mL, 29.1 mmol) was introduced over
approximately 10 min. Upon completion the cold bath was removed
and the mixture stirred for 30 min at r.t. The reaction vessel was
again cooled to 0 °C and CO2 was bubbled through the solution for
30 min at this temperature, then for 1 h at 20 °C. To this was added
allyl chloride (49 mL, 600 mmol) followed by PdCl2(MeCN)2 (389
mg, 1.5 mmol) as a solution in THF (5 + 3 mL). The reaction was
left stirring for 3 h at r.t. An approximately equal volume of aq
NH4Cl was added and the reaction contents transferred to a separat-
ing funnel with Et2O. The organic layer was isolated, the aq phase
back extracted one time with Et2O and the combined organics were
dried (MgSO4), filtered, and concentrated in vacuo. The crude resi-
due was purified by flash chromatography (5 to 17% EtOAc–hex-
anes) to afford the product as an oil.
Protocol B
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. It was then charged with 5 (95 mg,
0.5 mmol) and THF (2.5 mL). The resulting solution was cooled to
–78 °C and ZnCl2 (1 M in Et2O; 0.55 mL, 0.55 mmol) was added
followed by the addition of t-BuOK (0.6 mL, 0.6 mmol) over 2 min.
The reaction was left stirring for 10 min, then aq NH4Cl (2.0 mL)
was added and the mixture warmed to r.t. The reaction contents
were transferred to a separating funnel with additional aq NH4Cl
and Et2O and the organic layer isolated. The aq phase was extracted
once with Et2O and the combined organics were dried (MgSO4), fil-
tered, and concentrated in vacuo. The crude residue was purified by
flash chromatography (17% EtOAc–hexanes) to afford the desired
product as a solid.
Yield: 97%; white solid; Rf = 0.48 (25% EtOAc–hexanes);
mp 65 °C.
Yield: 23%; light yellow nonviscous volatile oil; Rf = 0.33 (17%
EtOAc–hexanes).
IR (thin film, CH2Cl2): 3035, 2980, 2933, 1745, 1456, 1369, 1276,
1158, 1100, 1042, 860, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.39–7.26 (m, 5 H), 6.00 (dd,
J = 8.8, 5.2 Hz, 1 H), 3.16 (dd, J = 16.8, 8.4 Hz, 1 H), 2.80 (dd,
J = 16.8, 5.2 Hz, 1 H), 2.14 (s, 3 H), 1.43 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 204.5, 152.5, 139.7, 128.7, 128.3,
126.3, 82.5, 74.4, 50.0, 30.5, 27.8.
IR (neat): 3081, 2920, 1825, 1732, 1372, 1185, 1131, 1050, 767
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.82–5.68 (m, 1 H), 5.16–5.15 (m,
1 H), 5.14–5.08 (m, 1 H), 5.06–5.02 (m, 2 H), 2.67–2.61 (m, 2 H),
1.81–1.77 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 153.3, 137.2, 133.3, 117.1, 109.1,
66.8, 35.6, 14.8.
HRMS (electrospray): m/z calcd for C15H20O4Na: 287.1264; found:
287.1257.
(4Z)-4-(1-Phenylbut-3-enylidene)[1,3]dioxolan-2-one (35)18
Prepared according to the protocol outlined for the preparation of
compound 34 with 3-phenyl-2-propyn-1-ol (4.16 g, 30 mmol). The
crude product was absorbed on silica, partially purified by flash
chromatography (5% EtOAc–hexanes) and was recovered as a
white solid (yield ca. 50%, contaminated). The recovered solid was
taken up in a minimum of warm Et2O, pentane was added as a non-
solvent and the product recrystallized by slow evaporation to yield
a solid.
In Situ Enolate Formation and Aldol or Mannich Reaction;
Mixture of tert-Butyl-(1S*,5R*)-5-hydroxy-3-oxo-1,5-diphenyl-
pentyl Carbonate and tert-Butyl-(1S*,5S*)-5-hydroxy-3-oxo-
1,5-diphenylpentyl Carbonate (28)
Representative Procedure (ZnCl2)
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. It was then charged with 5 (95 mg,
0.5 mmol) and THF (2.5 mL). The resulting solution was cooled to
–78 °C and t-BuOK (0.6 mL, 0.6 mmol) was added over 10 s, left
for 10 s, then ZnCl2 (0.6 mL, 0.6 mmol) was added over 10 s, and
the reaction mixture stirred an additional 5 min. Benzaldehyde (102
mL, 1.0 mmol) was then added dropwise and the temperature main-
tained for an additional 4 h. An approximately equal volume of aq
NH4Cl was added and the reaction vessel warmed to r.t. The con-
tents were then transferred to a separating funnel with Et2O and ad-
ditional aq NH4Cl , and the organic layer isolated. The aq layer was
back extracted with Et2O and the combined organics dried
(MgSO4), filtered, and concentrated in vacuo. The crude residue
was dried under high vacuum and the diastereomeric ratio deter-
Yiled: 26%; white granular solid; Rf = 0.28 (17% EtOAc–hexanes);
mp 59 °C.
IR (thin film, CH2Cl2): 3065, 2920, 1816, 1698, 1374, 1242, 1123,
764 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.47–7.43 (m, 2 H), 7.40–7.34 (m,
2 H), 7.31–7.25 (m, 1 H), 5.82–5.73 (m, 1 H), 5.14–5.07 (m, 4 H),
3.04–3.00 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 152.8, 138.7, 135.3, 133.3, 128.4,
127.9, 127.7, 116.8, 112.3, 67.4, 34.7.
HRMS (electrospray): m/z calcd for C13H12O3Na: 239.0678; found:
239.0674.
1
mined by H NMR (dr 1.8:1, diagnostic signals: major d = –5.18
(dd, J = 7.5, 4.3 Hz, 0.59 H); minor d = 5.12 (dd, J = 9.8, 2.5 Hz,
0.32 H). The crude residue was then purified by flash chromatogra-
phy (10 to 17% EtOAc–hexanes) to afford the product as an insep-
arable mixture of diastereomers.
Formation of b-Keto Carbonates; ( )-Carbonic Acid tert-Butyl
Ester 3-Oxo-1-phenylbutyl Ester (27)
Protocol A
Yield: 92%; colorless oil.
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. It was then charged with 5 (95 mg,
0.5 mmol) and THF (2.5 mL). The resulting solution was cooled to
–78 °C and t-BuOK (0.6 mL, 0.6 mmol) was added over 10 s, the
reaction was left for 10 s, then aq NH4Cl (2.0 mL) was added and
the mixture warmed to r.t. The reaction contents were transferred to
a separating funnel with additional aq NH4Cl and Et2O and the or-
ganic layer isolated. The aq phase was extracted once with Et2O and
the combined organics were dried (MgSO4), filtered, and concen-
trated in vacuo. The crude residue was purified by flash chromatog-
raphy (17% EtOAc–hexanes) to afford the desired product as a
white solid (yield 97%).
Representative Procedure (Bu2BOTf)
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. It was then charged with 5 (95 mg,
0.5 mmol) and THF (2.5 mL). The resulting solution was cooled to
–78 °C and t-BuOK (0.6 mL, 0.6 mmol) was added over 10 s, left
for 10 s, then Bu2BOTf (0.6 mL, 0.6 mmol) was added over 10 s and
the reaction mixture stirred an additional 5 min. Benzaldehyde (102
mL, 1.0 mmol) was then added dropwise and the temperature main-
tained for an additional 4 h. An approximately equal volume of aq
NH4Cl was added and the reaction vessel warmed to r.t. The con-
tents were then transferred to a separating funnel with Et2O and ad-
ditional aq NH4Cl and the organic layer was isolated. The aq layer
was back extracted with Et2O and the combined organics were dried
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

1406
M. L. Maddess, M. Lautens
PAPER
(MgSO4), filtered, and concentrated in vacuo. The crude residue
was diluted with Et2O (5 mL), NaOH (3 M; 1 mL) was added fol-
lowed by aq H2O2 (30%; 1 mL) and stirred slowly for 8 h (note typ-
ical phosphate buffered oxidation in MeOH causes destruction of
product). To this was then added aq NH4Cl and Et2O, the reaction
contents were transferred to a separating funnel and the organic lay-
er was isolated. The aq layer was extracted with Et2O, the combined
organics were dried (MgSO4), filtered, and concentrated in vacuo.
The crude reaction mixture was dried under high vacuum and the di-
astereomeric ratio determined by 1H NMR (dr 6.7:1, diagnostic sig-
nals: major d = –5.18 (dd, J = 7.5, 4.3 Hz, 1.0 H); minor d = 5.12
(dd, J = 9.8, 2.5 Hz, 0.14 H). The crude residue was then purified
by flash chromatography (10 to 17% EtOAc–hexanes) to afford the
product as an inseparable mixture of diastereomers.
1H NMR (300 MHz, CDCl3): d = 5.21 (d, J = 3.6 Hz, 1 H), 5.06 (d,
J = 3.6 Hz, 1 H), 4.99–4.88 (m, 1 H), 2.67 (dd, J = 15.3, 7.2 Hz, 1
H), 2.54 (dd, J = 15.3, 5.4 Hz, 1 H), 1.48 (s, 9H ), 1.34 (d, J = 6.3
Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 152.7, 152.5, 118.5 (q, J = 319
Hz), 107.1, 82.4, 69.9, 40.5, 27.7, 19.7.
19F NMR (282 MHz, CDCl3): d = –73.8.
HRMS (electrospray): m/z calcd for C11H17F3O6NaS: 357.0590;
found: 357.0602.
1-{(1R*,2S*)-2-[(tert-butoxycarbonyl)oxy]-1-methyl-2-phenyl-
ethyl}vinyl Trifluoromethanesulfonate (31)
Prepared according to the protocol outlined for the preparation of
compound 29 with 17 (102 mg, 0.50 mmol). The crude product was
purified by flash chromatography (0 to 5% Et2O–pentane) and was
recovered as an oil.
Yield: 83%; colorless oil; Rf = 0.14 (17% EtOAc–hexanes).
IR (neat): 3523, 2980, 1744, 1455, 1370, 1277, 1160, 1098, 1041
cm–1.
1H NMR (400 MHz, CDCl3): d = 7.41–7.30 (m, 10 H), 6.09–6.04
(m, 1 H), 5.23–5.11 (m, 1 H), 3.25–3.16 (m, 2 H), 2.95–2.75 (m, 3
H), 1.48 (m, 9 H).
13C NMR (100 MHz, CDCl3): d = 207.1, 206.9, 152.5, 142.6, 142.6,
139.4, 139.4, 128.7, 128.6, 128.4, 127.7, 126.3, 126.3, 125.6, 125.6,
82.7, 74.2, 74.1, 69.8, 69.7, 51.9, 50.0, 49.9, 27.8.
Yield: 82%; colorless oil; Rf = 0.41 (10% Et2O–pentane).
IR (neat): 2984, 1745, 1665, 1415, 1278, 938, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.39–7.31 (m, 5 H), 5.49 (d,
J = 8.8 Hz, 1 H), 5.23 (d, J = 4.0 Hz, 1 H), 5.03 (d, J = 4.0 Hz, 1
H), 2.94 (qd, J = 8.8, 7.2 Hz, 1 H), 1.42 (s, 9 H), 0.97 (d, J = 7.2 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 156.4, 152.4, 137.3, 128.6, 128.5,
127.2, 118.5 (q, J = 319), 82.6, 78.8, 44.4, 27.7, 14.5.
19F NMR (376 MHz, CDCl3): d = –74.2.
HRMS (electrospray): m/z calcd for C22H26O5Na: 393.1672; found:
393.1687.
Formation of Vinyl Triflates; ( )-1-{2-[(tert-Butoxycarbon-
yl)oxy]-2-phenylethyl}vinyl Trifluoromethanesulfonate (29);
General Procedure
HRMS (electrospray): m/z calcd for C17H21F3O6NaS: 433.0903;
found: 433.0909.
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. To this was added 5 (95 mg, 0.5
mmol) and THF (2.5 mL). The resulting solution was cooled to
–78 °C and t-BuOK (0.6 mL, 0.6 mmol) was added over 10 s, left
for 10 s, then (CF3SO2)2NPh (250 mg, 0.7 mmol) was added over
10 s as a solution in THF (0.6 mL). The resulting mixture was
stirred for 90 min, an approximately equal volume of H2O was add-
ed, and the cold flask warmed to r.t. The reaction contents were
transferred to a separating funnel with additional H2O and Et2O, and
the organic layer was isolated. The aq layer was extracted with
Et2O, and the combined organics were dried (MgSO4), filtered, and
concentrated in vacuo. The crude residue was purified by flash
chromatography (0 to 5% EtOAc–hexanes) to afford the product as
an oil.
( )-2-[(tert-Butoxycarbonyl)oxy]-2,6-dimethyl-1-methylene-
hept-5-enyl Trifluoromethanesulfonate (32)
Prepared according to the protocol outlined for the preparation of
compound 29 with 26 (98 mg, 0.50 mmol). The crude product was
purified by flash chromatography (0 to 5% Et2O–pentane) and was
recovered as an oil.
Yield: 94%; colorless oil; Rf = 0.36 (10% Et2O–pentane).
IR (neat): 2981, 2934, 1748, 1445, 1423, 1286, 1216, 1147, 944
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.41 (d, J = 4.5 Hz, 1 H), 5.32 (d,
J = 4.5 Hz, 1 H), 5.16–5.10 (m, 1 H), 2.11–1.86 (m, 4 H), 1.74 (s, 3
H), 1.72 (s, 3 H), 1.65 (s, 3 H), 1.53 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 155.1, 151.2, 132.8, 122.6, 118.3
(q, J = 315 Hz), 103.9, 82.6, 81.2, 37.1, 27.8, 25.8, 22.1, 22.0, 17.6.
19F NMR (282 MHz, CDCl3): d = –74.6.
Yield: 99%; colorless oil; Rf = 0.26 (5% EtOAc–hexanes).
IR (neat): 3414, 3068, 1671, 1672, 1445, 1419, 1214, 1130 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.40–7.30 (m, 5 H), 5.76 (dd,
J = 8.4, 4.8 Hz, 1 H), 5.18 (d, J = 3.6 Hz, 1 H), 4.99 (d, J = 3.6 Hz,
1 H), 2.96 (dd, J = 15.6, 8.4 Hz, 1 H), 2.77 (dd, J = 15.6, 4.8 Hz, 1
H), 1.44 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 152.4, 151.9, 138.6, 128.8, 128.6,
118.5 (q, J = 311 Hz), 82.8, 74.9, 41.4, 27.7.
HRMS (electrospray): m/z calcd for C16H25F3O6NaS: 425.1216;
found: 425.1225.
Formation of Silyl Enol Ethers; ( )-tert-Butyl 3-{[tert-Butyl-
(dimethyl)silyl]oxy}-1-phenylbut-3-enyl Carbonate (36);
General Procedure
19F NMR (376 MHz, CDCl3): d = –73.8.
A 10 mL round-bottom flask was flame dried under a stream of ni-
trogen and allowed to cool to r.t. To this was added 5 (95 mg, 0.5
mmol) and THF (2.5 mL). The resulting solution was cooled to
–78 °C and then t-BuOK (0.6 mL, 0.6 mmol) was added over 10 s,
left for 10 s, then neat TBSOTf (161 mL, 0.7 mmol) was added over
10 s. The reaction was stirred for 90 min, then an approximately
equal volume of aq NaHCO3 was added and the reaction warmed to
r.t. The contents were transferred to a separating funnel with aq
NaHCO3 and Et2O. The organic layer was isolated, the aq layer ex-
tracted with Et2O, and the combined organics were dried (MgSO4),
filtered and concentrated in vacuo. The crude residue was purified
by flash chromatography (5% Et3N, 5% EtOAc, 90% pentane) to af-
ford the product as an oil.
( )-1-{2-[(tert-Butoxycarbonyl)oxy]propyl}vinyl Trifluoro-
methylsulfonate (30)
Prepared according to the protocol outlined for the preparation of
compound 29 with 22 (68 mg, 0.50 mmol). The crude product was
purified by flash chromatography (0 to 5% Et2O–pentane) and was
recovered as an oil.
Yield: 97%; colorless oil; Rf = 0.43 (10% Et2O–pentane).
IR (neat): 2985, 1742, 1445, 1215, 1130, 942, 885 cm–1.
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

PAPER
Preparation and Utility of Cyclic Enol Carbonates
1407
Yield: 81%; colorless oil; Rf = 0.36 (5% Et3N, 5% EtOAc, 90%
pentane).
(s, 3 H), 1.54 (s, 3 H), 1.52 (m, 3 H), 1.42 (s, 9 H), 0.90 (s, 9 H), 0.16
(s, 6 H).
IR (neat): 2931, 2859, 1746, 1634, 1369, 1280, 1164, 1019 cm–1.
13C NMR (75 MHz, CDCl3): d = 158.5, 151.6, 131.7, 123.8, 88.3,
83.8, 81.2, 37.5, 27.9, 25.8, 25.7, 22.6, 22.5, 18.1, 17.6, –4.9, –5.0.
1H NMR (400 MHz, CDCl3): d = 7.37–7.25 (m, 5 H), 5.70 (dd,
J = 8.8, 5.6 Hz, 1 H), 4.05–4.04 (m, 2 H), 2.69 (dd, J = 14.0, 8.8
Hz, 1 H), 2.43 (dd, J = 14.0, 5.6 Hz, 1 H), 1.43 (s, 9 H), 0.95 (s, 9
H), 0.17 (s, 3 H), 0.16 (s, 3 H).
HRMS (electrospray): m/z calcd for C21H40O4NaSi: 407.2598;
found: 407.2591.
( )-tert-Butyl (3E)-3-{[tert-Butyl(dimethyl)silyl]oxy}-1-phenyl-
pent-3-enyl Carbonate (36) and ( )-tert-Butyl (3Z)-3-{[tert-Bu-
tyl(dimethyl)silyl]oxy}-1-phenylpent-3-enyl Carbonate (40)
Prepared according to the protocol outlined for the preparation of
compound 36 with 19 (115 mg, 0.56 mmol). Analysis of the crude
13C NMR (100 MHz, CDCl3): d = 154.6, 152.8, 140.4, 128.4, 127.9,
126.4, 92.1, 81.9, 76.3, 44.1, 27.8, 25.7, 18.1, –4.7, –5.0.
HRMS (electrospray): m/z calcd for C21H34O4NaSi: 401.2118;
found: 401.2123.
1
reaction mixture by H NMR indicated a ratio of E(O):Z(O) silyl
( )-tert-Butyl 3-{[tert-butyl(dimethyl)silyl]oxy}-1-[(E)-2-phenyl-
vinyl]but-3-enyl Carbonate (37)
Prepared according to the protocol outlined for the preparation of
compound 36 with 21 (42 mg, 0.19 mmol). The crude product was
purified by flash chromatography (2.5% Et3N–pentane) and was re-
covered as an oil.
enol ethers of ca. 4.2:1. The crude product was purified by flash
chromatography (0 to 4% Et2O in 0.5% Et3N–pentane) and was re-
covered as an inseparable mixture of olefin isomers. Spectral data
are reported only for the major component E(O) silyl enol ether.
Yield: 93%; colorless oil; Rf = 0.62 (5% Et2O, 0.5% Et3N, 94.5%
pentane).
IR (neat): 2931, 2859, 1743, 1672, 1472, 1368, 1279, 1165 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.40–7.24 (m, 5 H), 5.74 (dd,
J = 7.5, 7.0 Hz, 1 H), 4.63 (q, J = 7.0 Hz, 1 H), 2.75 (dd, J = 14.0,
7.5 Hz, 1 H), 2.47 (dd, J = 14.0, 7.0 Hz, 1 H), 1.42 (s, 9 H), 1.38 (d,
J = 7.0 Hz, 3 H), 0.94 (s, 9 H), 0.12 (s, 3 H), 0.12 (s, 3 H).
Yield: 80%; colorless oil; Rf = 0.73 (2.5% Et3N–pentane).
IR (neat): 2931, 2859, 1741, 1633, 1369, 1279, 1165, 1017, 840
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.47–7.28 (m, 5 H), 6.71 (d,
J = 15.9 Hz, 1 H), 6.24 (dd, J = 15.9, 7.5 Hz, 1 H), 5.49 (ddd,
J = 7.8, 7.5, 6.3 Hz, 1 H), 4.16 (m, 2 H), 2.63 (dd, J = 14.1, 7.8 Hz,
1 H), 2.44 (dd, J = 14.1, 6.3 Hz, 1 H), 1.54 (s, 9 H), 1.01 (s, 9 H),
0.24 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 152.7, 147.2, 140.5, 128.2, 127.8,
126.4, 103.1, 81.8, 76.8, 38.8, 27.8, 25.8, 18.1, 11.8, –4.4, –4.7.
HRMS (electrospray): m/z calcd for C17H27OSi [M – OC(O)OBoc]:
275.1825; found: 275.1820.
13C NMR (75 MHz, CDCl3): d = 154.7, 152.9, 136.6, 132.9, 128.7,
128.1, 127.2, 126.9, 92.3, 82.1, 75.3, 46.4, 42.4, 28.0, 25.9, 18.2,
–4.5, –4.7.
( )-tert-Butyl (3Z)-3-{[tert-Butyl(dimethyl)silyl]oxy}-1-phenyl-
pent-3-enyl Carbonate (41)
HRMS (electrospray): m/z calcd for C23H36O4NaSi: 427.2275;
found: 427.2289.
Prepared according to the protocol outlined for the preparation of
compound 36 with 20 (66 mg, 0.32 mmol). Analysis of the crude re-
action mixture by 1H NMR indicated a ratio of Z(O):E(O) silyl enol
ethers of >30:1. The crude product was purified by flash chromatog-
raphy (0 to 4% Et2O in 0.5% Et3N–pentane) and was recovered as
an oil. The assigned geometry of the silyl enol ether was consistent
with results of NOE experiments.
( )-tert-Butyl-3-{[tert-butyl(dimethyl)silyl]oxy}-1-methylbut-3-
enyl Carbonate (38)
Prepared according to the protocol outlined for the preparation of
compound 36 with 22 (68 mg, 0.50 mmol). The crude product was
purified by flash chromatography (2% Et3N–pentane) and was re-
covered as an oil.
Yield: 74%; colorless oil; Rf = 0.62 (5% Et2O, 0.5% Et3N, 94.5%
pentane).
Yield: 93%; colorless oil; Rf = 0.37 (2% Et3N–pentane).
IR: 2931, 2859, 1743, 1679, 1471, 1368, 1278, 1163, 1094 cm–1.
IR (neat): 2932, 2859, 1739, 1633, 1368, 1284, 1172, 1016, 839
cm–1.
1H NMR (300 MHz, CDCl3): d = 4.92 (qdd, J = 6.9, 6.9, 6.3 Hz, 1
H), 4.09–4.06 (m, 2 H), 2.44 (dd, J = 13.8, 6.9 Hz, 1 H), 2.16 (dd,
J = 13.8, 6.9 Hz, 1 H), 1.48 (s, 9 H), 1.28 (d, J = 6.3 Hz, 3 H), 0.93
(s, 9 H), 0.17 (s, 6 H).
1H NMR (400 MHz, CDCl3): d = 7.34–7.25 (m, 5 H), 5.75 (dd,
J = 8.4, 6.0 Hz, 1 H), 4.49 (q, J = 6.8 Hz, 1 H), 2.65 (dd, J = 14.4,
8.4 Hz, 1 H), 2.38 (dd, J = 14.4, 6.0 Hz, 1 H), 1.46 (d, J = 6.8 Hz, 3
H), 1.43 (s, 9 H), 0.98 (s, 9 H), 0.16 (s, 3 H), 0.13 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 152.8, 146.2, 140.5, 128.3, 127.8,
126.3, 105.4, 81.9, 76.4, 44.3, 27.8, 25.9, 18.3, 10.9, –3.8, –3.9.
13C NMR (75 MHz, CDCl3): d = 155.4, 153.0, 91.9, 81.6, 71.7, 43.2,
27.8, 25.7, 19.6, 18.0, –4.8, –4.9.
HRMS (electrospray): m/z calcd for C17H27OSi [M – OC(O)OBoc]:
275.1825; found: 275.1816.
HRMS (electrospray): m/z calcd for C16H32O4NaSi: 339.1962;
found: 339.1972.
( )-tert-Butyl-(3Z)-3-{[tert-butyl(dimethyl)silyl]oxy}-1,4-diphe-
nylbut-3-enyl Carbonate (42)
( )-tert-Butyl 1-(1-{[tert-Butyl(dimethyl)silyl]oxy}vinyl)-1,5-
dimethylhex-4-enyl Carbonate (39)
Prepared according to the protocol outlined for the preparation of
compound 36 with 26 (98 mg, 0.50 mmol). The crude product was
purified by flash chromatography (0 to 5% Et2O in 5% Et3N–pen-
tane) and was recovered as an oil.
Prepared according to the protocol outlined for the preparation of
compound 36 with 33 (27 mg, 0.10 mmol). Analysis of the crude re-
action mixture by 1H NMR indicated a single silyl enol ether. The
crude product was purified by flash chromatography (3% Et3N–
pentane) and was recovered as an oil.
Yield: 96%; colorless oil; Rf = 0.86 (5% Et2O, 5% Et3N, 90% pen-
tane).
Yield: 93%; colorless oil; Rf = 0.59 (3% Et3N–pentane).
IR: 2930, 2857, 1747, 1651, 1471, 1368, 1278, 1163, 986 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.41–7.32 (m, 6 H), 7.30–7.27 (m,
1 H), 7.24–7.20 (m, 2 H), 7.12–7.08 (m, 1 H), 5.88 (dd, J = 8.4, 6.0
Hz, 1 H), 5.47 (s, 1 H), 2.82 (dd, J = 14.4, 8.4 Hz, 1 H), 2.53 (dd,
IR (neat): 2932, 2859, 1745, 1632, 1464, 1369, 1285, 1109, 1070
cm–1.
1H NMR (300 MHz, CDCl3): d = 5.06–5.01 (m, 1 H), 4.27 (d,
J = 2.1 Hz, 1 H), 4.11 (d, J = 2.1 Hz, 1 H), 1.96–1.76 (m, 4 H), 1.63
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York

1408
M. L. Maddess, M. Lautens
PAPER
Hashimoto, H. Bull. Chem. Soc. Jpn. 1987, 60, 1204.
J = 14.4, 6.0 Hz, 1 H), 1.54 (s, 3 H), 1.40 (s, 9 H), 0.93 (s, 9 H), 0.01
(s, 6 H).
(c) Copper: Kwon, S.-C.; Cho, C.-S.; Shim, S.-C.; Kim, T.-
J. Bull. Korean Chem. Soc. 1999, 20, 103. (d) Phosphine:
Fournier, J.; Bruneau, C.; Dixneuf, P. H. Tetrahedron Lett.
1989, 30, 3981. (e) Strong base: Costa, M.; Chiusoli, G. P.;
Rizzardi, M. Chem. Commun. 1996, 1699. (f) Palladium:
Iritani, K.; Yanagihara, N.; Utimoto, K. J. Org. Chem. 1986,
51, 5499. (g) Palladium: Inoue, Y.; Itoh, Y.; Yen, I.-F.;
Imaizumi, S. J. Mol. Catal. 1990, 60, L1.
13C NMR (100 MHz, CDCl3): d = 153.0, 148.0, 140.3, 136.6, 128.9,
128.7, 128.2, 127.9, 126.5, 125.9, 111.7, 82.3, 76.7, 45.6, 28.0,
26.1, 18.5, –3.6.
HRMS (electrospray): m/z calcd for C22H29OSi [M – OC(O)OBoc]:
337.1982; found: 337.1966.
tert-Butyl-(2E)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-methyl-
hexa-2,5-dienyl Carbonate (43)
(4) Oxazolidinones, b-oxopropyl carbonates and carbamates:
(a) Joumier, J.-M.; Grainger, R.; Bruneau, C.; Dixneuf, P. H.
Synlett 1993, 423. (b) Laas, H.; Nissen, A.; Nurrenbbach, A.
Synthesis 1981, 958.
Prepared according to the protocol outlined for the preparation of
compound 36 with 34 (77 mg, 0.50 mmol). Analysis of the crude re-
action mixture by 1H NMR indicated a single silyl enol ether. The
crude product was purified by flash chromatography (0 to 5% Et2O
in 0.5% Et3N–pentane) and was recovered as an oil.
(5) Furanone derivatives and other heterocycles: (a) Joumier,
M.-M.; Fournier, J.; Bruneau, C.; Dixneuf, P. H. J. Chem.
Soc., Perkin Trans. 1 1991, 3271. (b) Inoue, Y.; Ohuchi, K.;
Imaizumi, S. Tetrahedron Lett. 1988, 29, 5941. (c) Inoue,
Y.; Matsushita, K.; Yen, I.-F.; Imaizui, S. Chem. Lett. 1991,
1377. (d) Ohe, K.; Matsuda, H.; Ishihara, T.; Ogoshi, S.;
Chatani, N.; Murai, S. J. Org. Chem. 1993, 58, 1173.
(e) Ohe, K.; Matsuda, H.; Morimoto, T.; Ogoshi, S.; Chatani,
N.; Murai, S. J. Am. Chem. Soc. 1994, 116, 4125.
(6) Cyclopropanes: Ogoshi, S.; Morimoto, T.; Nishio, K.-I.;
Ohe, K.; Murai, S. J. Org. Chem. 1993, 58, 9.
(7) Optically active bicyclic carbonates and 1,2-diols: Le
Gendre, P.; Braun, T.; Bruneau, C.; Dixneuf, P. H. J. Org.
Chem. 1996, 61, 8453.
(8) Marshall, J. A.; Yanik, M. M. J. Org. Chem. 1999, 64, 3798.
(9) Raimundo, B. C.; Heathcock, C. H. Org. Lett. 2000, 2, 27.
(10) Mahoney, W.; Brestensky, D.; Stryker, J. J. Am. Chem. Soc.
1988, 110, 291.
Yield: 99%; colorless oil; Rf = 0.56 (5% Et2O, 0.5% Et3N, 94.5%
pentane).
IR (neat): 2932, 2859, 1744, 1472, 1370, 1284, 1164, 997, 837 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.78–5.67 (m, 1 H), 5.30–4.97 (m,
2 H), 4.55 (s, 2 H), 2.80 (d, J = 5.2 Hz, 2 H), 1.64 (s, 3 H), 1.47 (s,
9 H), 0.95 (s, 9 H), 0.14 (s, 6 H).
13C NMR (100 MHz, CDCl3): d = 153.6, 140.4, 136.2, 119.4, 115.3,
81.8, 64.8, 37.2, 27.8, 25.9, 18.4, 16.1, –4.1.
HRMS (electrospray): m/z calcd for C18H34O4NaSi: 365.2118;
found: 365.2137.
tert-Butyl-(2Z)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-phenylhexa-
2,5-dienyl Carbonate (44)
Prepared according to the protocol outlined for the preparation of
compound 36 with 35 (108 mg, 0.50 mmol). Analysis of the crude
reaction mixture by 1H NMR indicated a single silyl enol ether. The
crude product was purified by flash chromatography (0.5% Et3N–
pentane) and was recovered as an oil.
(11) Additional details for the preparation of substrates including
isolation and characterization data are available upon
request.
(12) A procedure employing BuLi was also used extensively.
(13) Due to inseparable mixtures and low diastereomeric ratios,
full results are not reported at this time although
representative procedures are provided.
(14) McMurry, J. G.; Scott, W. J. Tetrahedron Lett. 1983, 24,
979.
(15) Purified by flash chromatography utilizing an eluent that
contained 0.5% Et3N. Trimethylsilyl and triethylsilyl
triflates gave products of low stability.
Yield: 97%; colorless oil; Rf = 0.74 (0.5% Et3N–pentane).
IR (neat): 3058, 2931, 2859, 1745, 1651, 1471, 1370, 1277, 1163,
1088 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.29–7.23 (m, 4 H), 7.21–7.15 (m,
1 H), 5.83–5.70 (m, 1 H), 5.07–4.94 (m, 2 H), 4.67 (s, 2 H), 3.15 (d,
J = 5.7 Hz, 2 H), 1.50 (s, 9 H), 0.71 (s, 9 H), –0.21 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 153.8, 142.3, 140.3, 136.3, 129.6,
(16) To the best of our knowledge neither vinyl triflates nor silyl
enol ethers containing a b-tert-butyl carbonate moiety have
previously been prepared. Nor have the parent ketone
compounds ever been used directly in an aldol or Michael
reaction. This is perhaps a reflection of their base sensitivity.
(17) Prepared by modification of a literature protocol: Touleec,
P.; Martin, A. C.; Gio-Batta, M.; Bruneau, C.; Dixneuf, P. H.
Tetrahedron Lett. 2000, 41, 5527.
128.0, 126.6, 123.3, 115.5, 82.3, 65.7, 37.4, 28.0, 25.7, 18.3, –4.5.
HRMS (electrospray): m/z calcd for C23H36O4NaSi: 427.2275;
found: 427.2287.
Acknowledgment
(18) Prepared by modification of a literature protocol: Iritani, K.;
Yanagihara, N.; Utimoto, K. J. Org. Chem. 1986, 51, 5501.
(19) From ketenes, see: (a) Haner, R.; Laube, T.; Seebach, D. J.
Am. Chem. Soc. 1985, 107, 5396. (b) Baigrie, L. M.; Lenoir,
D.; Seikaly, H. R.; Tidwell, T. T. J. Org. Chem. 1985, 50,
2105. (c) Baigrie, L. M.; Seikaly, H. R.; Tidwell, T. T. J. Am.
Chem. Soc. 1985, 107, 5391. (d) O’Neill, P.; Hegarty, A. F.
J. Org. Chem. 1987, 52, 2113.
(20) From allylic alkoxides, see: Gazzard, L. J.; Motherwell, W.
B.; Sandham, D. A. J. Chem. Soc., Perkin Trans. 1 1999, 8,
979.
(21) From esters (cyclic), see: Fehr, C.; Galindo, J. J. Org. Chem.
1988, 53, 1830.
We thank Merck Frosst Canada and NSERC (Canada) for an IRC,
and the University of Toronto for financial support of this work. M.
M. thanks NSERC (Canada) for financial support in the form of a
postgraduate fellowship.
References
(1) (a) Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S. J. Chem.
Soc., Chem. Commun. 1981, 465. (b) Bongini, A.; Cardillo,
G.; Orena, M.; Porzi, G.; Sandri, S. J. Org. Chem. 1982, 47,
4626.
(2) (a) Bartlett, P. A.; Meadows, J. D.; Brown, E. G.; Morimoto,
A.; Jernstedt, K. K. J. Org. Chem. 1982, 47, 4013.
(b) Smith, A. B.; Duan, J. J.-W. J. Org. Chem. 1993, 58,
3703.
(22) For spectral details, see for example: Cardillo, G.; Orena,
M.; Porzi, G.; Sandri, S.; Tomasini, C. J. Org. Chem. 1984,
49, 701.
(3) (a) Ruthenium: Sasaki, Y. Tetrahedron Lett. 1986, 27,
1573. (b) Cobalt: Inoue, Y.; Ishikawa, J.; Taniguchi, M.;
Synthesis 2004, No. 9, 1399–1408 © Thieme Stuttgart · New York