Studies on the synthesis of 2,6-disubstituted dihydropyrans: Intervention of oxonia-cope rearrangements in the lewis acid mediated cyclodehydrative reactions of aldehydes and β-hydroxyallylsilanes

Article abstract of DOI:10.1055/s-2001-14632

The dehydrative coupling reactions of anti-β-hydroxyallylsilanes 5 and aldehydes provide 2,6-cis-dihydropyrans 27 by pathways involving oxonium ions that cyclize via boat-like transition state 21, with the intervention of oxonia-Cope rearrangements (21 → 29).

Full text of DOI:10.1055/s-2001-14632

LETTER
955
Studies on the Synthesis of 2,6-Disubstituted Dihydropyrans: Intervention of
Oxonia-Cope Rearrangements in the Lewis Acid Mediated Cyclodehydrative
Reactions of Aldehydes and -Hydroxyallylsilanes
William R. Roush,* Garrett J. Dilley1
Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109-1055, USA
Fax +1 734 6479279; E-mail: roush@umich.edu
Received 22 January 2001
Dedicated to Professor Ryoji Noyori in admiration of his seminal contributions to organic chemistry.
Me
Abstract: The dehydrative coupling reactions of anti- -hydroxyal-
OMe
lylsilanes 5 and aldehydes provide 2,6-cis-dihydropyrans 27 by
Me
Me
Me
Me
pathways involving oxonium ions that cyclize via boat-like transi-
tion state 21, with the intervention of oxonia-Cope rearrangements
(21 29).
O
OMe OMe
CHO
N
Me
Me
OH
O
OMe
Me
O
Key words: addition reactions, intramolecular allylations, sigma-
tropic rearrangement, allylsilanes, dihydropyrans
scytophycin C
OH
O
Me
Me
Me
Me
OTBDPS
OHC
OHC
SiMe2R
During the course of our work on the total synthesis of
scytophycin C,2 we became interested in developing a
new strategy for synthesis of the 2,6-trans disubstituted
dihydropyran nucleus of 4 by the late stage coupling of
two advanced aldehyde fragments (1 and 2) with the bi-
functional allylating agent, 3 (X2 = DIPT or Ipc2).3,4 While
numerous strategies for synthesis of substituted pyrans are
available,5 none have the potential modularity of the
method that we sought to develop.
dehydrative
coupling
OMe OMe OMe
Me
O
OTBS
PMBM
1
BX2
CO2Me
3
OTBS
Me
2
Me
Me
Me
OTBDPS
O
OMe OMe OMe
Me
O
OTBS
PMBM
CO2Me
The plan was that -hydroxyallylsilanes 5, which are
available with high diastereo- and enantioselectivity via
the asymmetric -silylallylboration of aldehydes with al-
lylborane reagents 3,3,4,6 would combine with a second al-
dehyde in the presence of a Lewis acid to give oxonium
ion 6, which would then undergo an intramolecular allyla-
tion to produce the 2,6-trans-disubstituted dihydropyran
7.7,8 This process is related to the well established Prins
cyclization reactions of homoallylic alcohols and alde-
hydes, which provide cis-2,6-disubstituted dihydropyrans
preferentially.9-14 However, owing to the strong stereo-
electronic preference for the silyl substituent to adopt an
axial position in reactions that develop carbocationic
character at the -position,15,16 we expected that the con-
version of 5 to 7 would provide the 2,6-trans-dihydropyr-
an selectively. Implicit in this prediction was the
assumption that the intramolecular allylation would pro-
ceed by way of a chair-like transition state (as in 6). The
stereochemistry of the trans-dihydropyran product then
follows from the 3,4-anti stereochemistry of the allylsi-
lane 5, which dictates that both the R group (deriving from
the aldehyde used in the synthesis of 5) and the silyl sub-
stituent will adopt axial positions in 6, and the equatorial
placement of the R’ substituent (deriving from the second
aldehyde, R’CHO).
4
OTBS
R'
R
OH
R'CHO
Lewis acid
O
R'
R
O
R
SiMe3
SiMe3
5
6
7
No examples of intramolecular allylation of the type 5 to
7 had been reported at the time that our studies were initi-
ated.7,8 However, Speckamp had suggested that ions like
6 (with R’ = CO2Me) are intermediates in the vinylsilane-
terminated cyclizations of ester-substituted oxocarbenium
ions.17,18 Consequently, we anticipated that our method
would intercept a known class of reactive intermediates
by starting from 5, rather than from a vinylsilane precur-
sor.8,19 While our studies were in progress, Panek reported
an analogous method for the synthesis of substituted dihy-
dropyrans via the reactions of -hydroxycrotylsilanes and
aldehydes.5
Synlett 2001 SI, 955–959 ISSN 0936-5214 © Thieme Stuttgart · New York

956
W. R. Roush, G. J. Dilley
LETTER
Initial studies were performed using allylsilane 8a4 and sired product 12 (12%), dihydropyran 13 (17%) that
the corresponding TMS ether 8b as substrates. After differs from 12 in terms of the placement of the double
screening a number of Lewis acid and solvent combina- bond in the ring, and dihydropyran 9 (7%) with two phe-
tions, we settled on use of TMS-OTf in CH2Cl2 at -78 °C nylethyl substituents! The same three products were ob-
in the presence of 4Å molecular sieves for these reac- tained (70% combined yield) from the reaction of
tions.20,21 The optimal conditions for the reaction of 8a allylsilane 14 with dihydrocinnamaldehyde (4 equiv.). In
with dihydrocinnamaldehyde involved use of 3 equiv. of this case, the bis-phenylethyl substituted cis-dihydropyr-
the aldehyde and 0.5 equiv. of TMS-OTf at a final concen- an 9 was obtained in 50% yield, with the desired product
tration of 0.15 M (for 8a). Under these conditions, an 82% 13 being isolated in 17% yield along with the olefin regio-
yield of dihydropyran 9 was obtained with excellent stere- isomer 12 in 3% yield (after HPLC separation). The cis-
oselectivity (94: 6 d.s.). Comparative experiments using stereochemistry of dihydropyrans 12 and 13 was assigned
8a and the TMS ether 8b indicated that there was no sig- by 1H NOE studies.
nificant advantage to use of 8b as the substrate. However,
use of smaller amounts of aldehyde led to substantially
decreased yields owing to competitive Lewis acid cata-
OH
lyzed Peterson elimination of 8a/8b, as well as the TMS-
OTf promoted cyclotrimerization of the aldehyde. The
Peterson elimination process was completely suppressed
using the optimal conditions (3 equiv. RCHO, 0.5 equiv.
TMS-OTf, 0.15 M concentration of 8a).
(1 equiv)
CHO
Ph
TMS-OTf (0.5 equiv)
CH2Cl2, 4Å sieves
-78 °C
SiMe3
8a
Ph
Ph
O
O
O
+
+
Ph
CHO
OX
Ph
O
Ph
Ph
h
12, 12%
13, 17%
9, 7%
TMS-OTf, CH2Cl2
4 Å sieves, -78 °C
SiMe3
9
8a, X = H
Ph
8b, X = TMS
CHO
OH
(4 equiv)
Ph
Substrate RCHO
TMS-OTf
1.0 eq.
0.5 eq.
0.5 eq.
0.5 eq.
Conc.
0.08 M
0.14 M
0.13 M
0.15 M
Yield
d.s
TMS-OTf (0.5 equiv)
CH2Cl2, 4Å sieves
-78 °C
8b
8b
8a
8a
1.0 eq.
1.0 eq.
1.0 eq.
3.0 eq.
49%
38%
n.d.
91 : 9
94 : 6
95 : 5
94 : 6
SiMe3
14
82%
Ph
Ph
O
O
O
Ph
+
+
CHO
OH
Ph
(3 eq.)
O
BuO2C
Ph
Ph
BuO2C
TMS-OTf, CH2Cl2
4 Å sieves, -78 °C
55%
SiMe3
12, 3%
13, 17%
9, 50%
11, d.s. 85 : 15
10
The side chain exchange process that complicates the re-
actions of allylsilanes 8a and 14 leading to unsymmetri-
cally substituted dihydropyrans 12 and 13 can be
suppressed by using -acetoxy acetals such as 16 and 19
as the cyclization substrates. The -acetoxy acetals were
synthesized by using Rychnovsky’s procedure for in situ
acylation of the tetrahedral intermediates generated by
DIBAL reduction of esters.22-24 The optimal conditions
for cyclization of 16 involved use of SnCl4 (1.5 equiv.) in
toluene at -78 °C to -15 °C. Under these conditions, the
2,6-cis-dihydropyran 17 was obtained in 66% yield with
94: 6 d.s., and the symmetrically substituted dihydropyran
9 (resulting from side chain exchange) was obtained in
only 4% yield. As another illustration of this method, cis-
dihydropyran 9 was obtained in 50% overall yield (94: 6
d.s.) for the three step sequence from 18.
Surprisingly, the major product of the reaction of 8a and
dihydrocinnamaldehyde was the 2,6-cis-dihydropyran 9,
and not the originally targeted trans diastereomer. The
stereochemistry of 9 was easily assigned by hydrogena-
tion (H2, Pd/C) to the meso tetrahydrofuran ([ ]D = 0), as
well as by the observation of an NOE between the two ax-
ial hydrogens at C(2) and C(6) of 9. The reaction of 10 and
dihydrocinnamaldehyde similarly provided dihydropyran
11 (85: 15 d.s., 57% yield), again with the cis-isomer pre-
dominating (as confirmed by an NOE between H-2 and H-
6).
Attempts to extend these results to additional hydroxyal-
lylsilane-aldehyde combinations led to complex product
mixtures. For example, the reaction of allylsilane 8a with
isobutyraldehyde (1.0 equiv., using non-optimized condi-
tions) gave three products after HPLC separation: the de-
Synlett 2001, SI, 955–959 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Studies on the Synthesis of 2,6-Disubstituted Dihydropyrans
957
facile oxonia-Cope rearrangements17,18,25 in the intramo-
lecular allylation process.26 We assumed at the outset that
oxonium ion 22 (c.f., 6) would cyclize via a chair-like
transition state to give the 2,6-trans-dihydropyran 23 (c.f.,
7). However, the experimental record clearly establishes
that this pathway (22 23) is slow. We initially speculat-
ed that ion 22 undergoes a [3,3]-sigmatropic rearrange-
ment, or an oxonia-Cope rearrangement, to give 24 in
which the phenylethyl substituent adopts a thermodynam-
ically unfavorable axial position. Oxonium ion 24 could
isomerize to 25 with an equatorial phenylethyl substitu-
ent, by reversible addition of a nucleophile (e.g., TMS-
OH in the TMS-OTf catalyzed reactions of 8a; chloride or
acetate ions in the SnCl4 promoted reactions of the -ace-
toxy acetals, 20). Ion 25 is structurally equivalent to the
intermediates generated by Speckamp and Markó from
homoallylsilanols like 28.8,17-19 It could be expected that
25 would cyclize directly to the 2,6-cis-dihydropyran ent-
27,27 or undergo a facile reverse oxonia-Cope rearrange-
ment to 26 which can then undergo intramolecular allyla-
tion to the 2,6-cis-disubstituted dihydropyran ent-27. The
intermediacy of ions 24 and 25 also accounts for the side
chain scrambling that occurs in the reaction of 8a with
isobutyraldehyde and of 16 with dihydrocinnamaldehyde,
as addition of TMS-OH to 24 or 25 creates the opportunity
for release of dihydrocinnamaldehyde into solution and
give 28, which can then recombine with the second alde-
hyde, R’CHO, which is used in excess.28
O
OAc
1) DIBAL
-78 °C
O
C6H4OMe
O
Ar
Ph
Ph
2) Ac2O
pyr, DMAP
SiMe3
SiMe3
15
16
77-79%
TMS-OTf
(CH2Cl2,
SnCl4
(toluene
-78 °C) -78° to -15°C)
Ph
O
O
C6H4OMe
50% yield 66% yield
(94 : 6 d.s.) (94 : 6 d.s.)
17
9
Lewis
acid
Ph
3% yield
4% yield
OAc
Ph
O
1) DIBAL,
-78 °C
O
Ph
O
Ph
Ph
Ph
2) Ac2O, pyr
DMAP
SiMe3
SiMe3
18
19
SnCl4
Ph
O
Ph
toluene, -78 °C
50% from 18
(94 : 6 d.s.)
9
The preferential formation of the 2,6-cis-dihydropyrans
and the unanticipated exchange of allylsilane side chains
can be explained by invoking competitive and extremely
R'
R'
O
O
Ph
Ph
Prediction:
ent-27, 2,6-cis
23, 2,6-trans
inversion of original
C-O stereochemistry
via chair t.s. 25
Ph
slow
H
H
R
R'
R'
R'
R'
O
O
O
O
R
22
24
25
26
SiMe3
SiMe3
SiMe3
SiMe3
Ph
SnCl4
-78 °C
-PhCH2CH2CHO
R'
SnCl4
-78 °C
O
OAc
R'
R'
R'
R
R
O
O
OH
Ph
SiMe3
SiMe3
SiMe3
SiMe3
29
H
28
20
21
R'CHO
TMS-OTf
R'
O
Prediction:
OH
retention of original
C-O stereochemistry
via boat t.s. 21
Ph
Ph
SiMe3
27, 2,6-cis
8a
Scheme Intervention of Oxonia-Cope Rearrangements in the Intramolecular Allylation Reaction
Synlett 2001, SI, 955–959 ISSN 0936-5214 © Thieme Stuttgart · New York

958
W. R. Roush, G. J. Dilley
LETTER
A striking conclusion of this analysis is that if this process
proceeds via the intermediacy of chair-like transition
states, the 2,6-cis-dihydropyran ent-27 will be produced
with inversion of the original C-O stereochemistry of 8a.
This stereochemical inversion occurs at the stage of the
OAc
SnCl4
toluene, -78 °C
O
O
Ph
Ph
Ph
Ph
Ph
50% (from 18)
SiMe3
oxonium ion isomerization, 24
25. However, if the
19, 93% e.e.
9, 94% e.e.
retention
oxonia-Cope rearrangements and the intramolecular ally-
lation proceed by way of boat-like transition structures 21
and 29, then the overall conversion of 8a or 20 to the 2,6-
cis-dihydropyran 27 will proceed with retention of ste-
reochemistry.
CHO
OH
Ph
O
(3 eq)
Ph
Ph
TMS-OTf, CH2Cl2
4Å sieves, -78 °C
80%
SiMe3
ent-9, 87% e.e.
ent-8a, 87% e.e.
We established that the cyclization reactions of the -ace-
toxy acetals proceed with retention of stereochemistry by
the synthesis of 33, a known precursor of a civet cat pher-
omone.29,30 Thus, treatment of -acetoxy acetal 31, pre-
pared in 75% yield from ester 3031 by using the
Rychnovsky procedure,22,23 with TMS-OTf in CH2Cl2 at -
78 °C provided 32 in 41% yield (volatile!) with 94: 6 se-
lectivity. The 2,6-cis stereochemistry was confirmed by
the observation of a NOE between H-2 and H-6. Hydro-
genation of 32 over Pd/C provided (–)-33, the stere-
ochemistry of which was confirmed by comparison with
two independent literature assignments. 29,30
retention
CHO
Ph
OH
O
(4 eq)
Ph
Ph
TMS-OTf, CH2Cl2
4Å sieves, -78 °C
50%
SiMe3
9, 86% e.e.
retention
14, 88% e.e.
Based on these results, we conclude that all of the in-
tramolecular allylation reactions leading to 2,6-cis-disub-
stituted dihydropyrans described in this paper, as well as
the oxonia-Cope rearrangement reactions implicated in
the side chain exchange process, proceed with high stere-
ochemical fidelity via boat-like transition states (e.g., 8a/
20 21 27 for the allylation, and 8a 21 29 28
29 21 27 for the allylation process with exchange
of the allylsilane side chain; see Scheme). Our results also
explain the preferential formation of 2,6-cis-disubstituted
dihydropyrans from the InCl3 mediated reactions of alde-
hydes and 3-trimethylsilylallyl tributylstannane recently
described by Li and coworkers.9
O
OAc
1) DIBAL, -78 °C
O
OBn
O
OBn
OH
Me
Me
2) Ac2O, DMAP
75%
SiMe2Ph
SiMe2Ph
30
31
OBn
H2, Pd/C
MeOH
TMS-OTf
O
O
CH2Cl2, -78°C
Me
Me
We conclude by commenting briefly on the related dihy-
dropyran synthesis recently reported by Panek.5 The de-
hydrative cyclizations of crotylsilanes 34 and 36 proceed
with excellent selectivity to the substituted dihydropyrans
41%
32
33, [α]D -23.3 °
lit. [α]D -18.9 °
Armed with the knowledge that the cyclization of -ace-
toxy acetals proceeds with retention of stereochemistry,
we established the absolute stereochemical course of the
allylation reactions of hydroxyallylsilanes as well as the
stereochemistry of the allylation process involving side
chain scrambling. First, we showed that the SnCl4 promot-
ed cyclization of 19 (93% e.e.) provides 9 (94% e.e.) with
complete retention of stereochemistry as determined by
chiral HPLC analysis. The TMS-OTf catalyzed dehydra-
tive coupling of ent-8a (87% e.e.) and dihydrocinnimalde-
hyde similarly proceeded with complete retention of
stereochemistry, as cis-2,6-dihydropyran ent-9 was ob-
tained with 87% e.e. Finally, dihydropyran 9 (86% e.e.)
was obtained from the dehydrative coupling of 14 (88%
e.e.) and dihydrocinnamaldehyde that proceeds by way of
vinylsilane 28 (R’ = PhCH2CH2-) with three C-C bond
forming reactions and loss of isobutyraldehyde from the
starting allylsilane.
OTMS
cat. TMSOTf
RCHO
Me
R
Me
Me
CO2Me
SiMe2Ph
MeO2C
O
CH2Cl2, -20 °C
78-87%
34
35, 9 - 15 : 1 d.s.
OTMS
Me
CO2Me
SiMe2Ph
MeO2C
O
R
36
37, 10 - 30 : 1 d.s.
CO2Me
Me
O
Me
O
R
R
E
SiMe2Ph
SiMe2Ph
38
40
Me
Me
R
R
CO2Me
SiMe2Ph
O
O
SiMe2Ph
CO2Me
39
41
Synlett 2001, SI, 955–959 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Studies on the Synthesis of 2,6-Disubstituted Dihydropyrans
959
MeOB(Ipc)2 at -78 °C, BF3 Et2O and then an aldehyde (see
ref. 4 for a related procedure), or by using the DIPT modified
(E)- -trimethylsilylallylboronate (Marron, T. G.; Roush, W.
R. Tetrahedron Lett. 1995, 36, 1581).
35 and 37, respectively. While Panek has suggested that
these reactions proceed by way of boat-like transition
states,32 we think it is more likely that they proceed by
way of the chair like transition structures 38 (for 34) and
40 (for 36) because the boat-like transition states 39 and
41 (in which the oxonium ions adopt the more stable (E)-
geometry) suffer from eclipsing interactions involving the
aldehyde R group and the Me group deriving from the cro-
tylsilane reagent; transition structure 39 also suffers from
an eclipsing interaction between the axial carbomethoxyl
and the pseudoaxial -SiMe2Ph.
(7) Markó, I.; Mekhalfia, A. Tetrahedron Lett. 1992, 33, 1799.
(8) Markó, I. E.; Bayston, D. J. Tetrahedron 1994, 50, 7141.
(9) Viswanathan, G. S.; Yang, J.; Li, C.-J. Org. Lett. 1999, 1, 933.
(10) Cloninger, M. J.; Overman, L. E. J. Am. Chem. Soc. 1999,
121, 1092.
(11) Rychnovsky, S. D.; Hu, Y.; Ellsworth, B. Tetrahedron Lett.
1998, 39, 7271.
(12) Markó, I.; Chellé, F. Tetrahedron Lett. 1997, 38, 2895.
(13) Markó, I. E.; Mekhalfia, A.; Bayston, D. J.; Adams, H. J. Org.
Chem. 1992, 57, 2211.
Based on these results, it appears that the boat-like transi-
tion state 21 in the reactions of the allylsilanes reported
herein is favored owing to the absence of the eclipsing in-
teractions highlighted in 39 and 41. Finally, we note that
products deriving from oxonia-Cope rearrangements were
not observed in the Panek study, a result that is consistent
with the dehydrative cyclization reactions of car-
boalkoxy-substituted allylsilane 10. It may be inferred
that the oxonia-Cope process is disfavored with interme-
diates 21 (R = CO2Bu) since the electron withdrawing
carboalkoxy group destabilizes the oxonia-Cope product
29 in which the -CO2Bu group is directly attached to the
oxonium ion carbon. If this analysis is correct, then the de-
hydrative cyclization reactions of aldehydes and crotylsi-
lanes analogous to 8a and 14, etc., will also experience
competitive oxonia-Cope processes.
(14) Coppi, L.; Ricci, A.; Taddei, M. J. Org. Chem. 1988, 53, 911.
(15) Lambert, J. B.; Finzel, R. B. J. Am. Chem. Soc. 1982, 104,
2020.
(16) Lambert, J. B.; Wang, G.-T. J. Phys. Org. Chem. 1988, 1, 169.
(17) Lolkema, L. D. M.; Semeyn, C.; Ashek, L.; Hiemstra, H.;
Speckamp, W. N. Tetrahedron 1994, 50, 7129.
(18) Semeyn, C.; Blaauw, R. H.; Hiemstra, H.; Speckamp, W. N.
J. Org. Chem. 1997, 62, 3426.
(19) Markó, I. E.; Dobbs, A. P.; Scheirmann, V.; Chellé, F.;
Bayston, D. J. Tetrahedron Lett. 1997, 38, 2899.
(20) Imwinkelried, R.; Seebach, D. Angew. Chem. Int. Ed. Engl.
1985, 24, 765.
(21) Mekhalfia, A.; Markó, I. Tetrahedron Lett. 1991, 32, 4779.
(22) Dahanukar, V. H.; Rychnovsky, S. D. J. Org. Chem. 1996, 61,
8317.
(23) Kopecky, D. J.; Rychnovsky, S. D. J. Org. Chem. 2000, 65,
191.
(24) Esters 15 and 18 were prepared by acylation of 8a with the
appropriate acid chlorides (DMAP, pyridine, CH2Cl2) in 82-
84% yield.
(25) Sumida, S.; Ohga, M.; Mitani, J.; Nokami, J. J. Am. Chem.
Soc. 2000, 122, 1310.
(26) Analogous aza-Cope rearrangements of iminium ions have
been documented previously: Daub, G. W.; Heerding, D. A.;
Overman, L. E. Tetrahedron 1988, 44, 3919.
Additional studies on the stereoselective synthesis of 2,6-
trans-disubstituted dihydropyrans, required for our syn-
thesis of scytophycin C and other natural products, are on-
going and will be reported in due course.
Acknowledgement
(27) Blumenkopf, T. A.; Overman, L. E. Chem. Rev. 1986, 88, 857.
(28) Loss of the original side chain also occurs in iminium ion-
vinylsilane cycilzations which proceed via aza-Cope
rearrangements: Castro, P.; Overman, L. E.; Zhang, X.;
Mariano, P. S. Tetrahedron Lett. 1993, 34, 5243.
(29) Mandai, T.; Ueda, M.; Kashiwagi, K.; Kawada, M.; Tsuji, J.
Tetrahedron Lett. 1993, 34, 111.
(30) Edmunds, A. J. F.; Trueb, W. Tetrahedron Lett. 1997, 38,
1009.
(31) Chiral allylsilane 30 was synthesized from the corresponding
homoallylic silanol that was prepared as described in ref. 4.
The absolute stereochemistry of the alcohol was assigned by
using the modified Mosher ester method.
We gratefully acknowledge support provided the National Institute
of General Medical Sciences (GM 38436).
References and Notes
(1) Taken in part from the 2000 Ph. D. Thesis of G. J. Dilley,
University of Michigan.
(2) Roush, W. R.; Dilley, G. J. Tetrahedron Lett. 1999, 40, 4955.
(3) Roush, W. R.; Grover, P. T. Tetrahedron 1992, 48, 1981.
(4) Roush, W. R.; Pinchuk, A. N.; Micalizio, G. C. Tetrahedron
Lett. 2000, 41, 9413.
(5) Huang, H.; Panek, J. S. J. Am. Chem. Soc. 2000, 122, 9836,
and references cited therein.
(6) Allyltrimethylsilanes of general structure 5 were synthesized
by allylboration of aldehydes with the chiral allylborane
reagent generated by metallation of allyltrimethylsilane with
n-BuLi and KOtBu in THF at -25 °C followed by addition of
(32) Panek's analysis indicates that the favored boat-like transition
states have the thermodynamically less favorable (Z)-
oxonium ion geometry.
Article Identifier:
1437-2096,E;2001,0,SI,0955,0959,ftx,en;Y02301ST.pdf
Synlett 2001, SI, 955–959 ISSN 0936-5214 © Thieme Stuttgart · New York