Studies toward the generation of functionalized quaternary carbon centers relying on wittig and wittig-still allylic ether anionic transpositions

Article abstract of DOI:10.1021/jo401488y

Although the [2,3]-Wittig and Wittig-Still rearrangements have long been known, their application in the generation of quaternary carbon centers in carbocyclic ring systems is sparse. Model studies utilizing this strategy and possible mechanisms are discussed herein. Unprecedented examples of an α-elimination pathway from stannylmethyl allyl ethers as a major undesired product in some Wittig-Still rearrangements are reported.

Full text of DOI:10.1021/jo401488y

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Note
Studies toward the generation of functionalized quaternary carbon centers
relying on Wittig and Wittig-Still allylic ether anionic transpositions
Stephen Hanessian, Stéphane Dorich, Amit Kumar Chattopadhyay, and Martin Büschleb
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo401488y • Publication Date (Web): 05 Aug 2013
Downloaded from http://pubs.acs.org on August 14, 2013
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Studies toward the generation of functionalized quaternary carbon
centers relying on Wittig and WittigꢀStill allylic ether anionic
transpositions
Stephen Hanessian,* Stéphane Dorich, Amit Kumar Chattopadhyay, Martin Büschleb
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Department of Chemistry, Université de Montréal, Station Centre Ville, C.P. 6128, Montreal, Qc, H3C 3J7
(Canada).
*Eꢀmail: stephen.hanessian@umontreal.ca
OH
O
SnBu3
OH
OH
R
+
+
n
n
n
n
R
R
R
R = alkyl, alkenyl
[2,3]-shift
[1,2]-shift
"demethylstannylation"
ABSTRACT: Although the [2,3]ꢀWittig and WittigꢀStill rearrangements have long been known, their application in
the generation of quaternary carbon centers in carbocyclic ring systems is sparse. Model studies utilizing this
strategy and possible mechanisms are discussed herein. Unprecedented examples of an αꢀelimination pathway from
stannylmethyl allyl ethers as a major undesired product in some WittigꢀStill rearrangements are reported.
The formation of CꢀC bonds to generate quaternary carbon centers remains as a major challenge in organic
functional group transformations.1 Apart from synthetic and mechanistic considerations, securing relative or
absolute stereochemistry at the newly created quaternary carbon center can be a daunting task.2 Elegant solutions to
such problems have been found in the context of natural product synthesis, where specific methods were adapted to
the target molecule in question.3 Clearly, steric congestion, proximity effects, and propensities for skeletal
rearrangements present major obstacles in arriving at a predictable outcome of reactions leading to quaternary
carbon centers. Cognizant of these challenges, methods are constantly sought which introduce quaternary carbon
atoms relying on energetically favorable transition states, and under mild conditions.
Among such methods are allylic ether transpositions involving carbanionic intermediates that take place at
o
temperatures as low as ꢀ100 C. In this context, the [2,3]ꢀWittig rearrangement4 of allylic ethers is a wellꢀknown
process to transpose an allylic alcohol group to the distal carbon atom. In the case of doubly allylic ethers, the less
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substituted allylic moiety is rearranged to give 1,5ꢀdienꢀ3ꢀols, although different pathways leading to other products
are also possible.5
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An extension of the [2,3]ꢀWittig rearrangement, introduced by Still and Mitra,6 involves the formal transfer of a
hydroxymethyl group from a tributylstannylmethyl allylic ether onto the distal olefinic carbon atom. Early examples
include applications in the synthesis of dendrolasin,7 plumericin,8 12,25ꢀdihydroxyvitamin D,9 and laurenene
intermediates.10 Although extensively studied over the years, examples of creating quaternary carbon centers using
[2,3]ꢀWittig or [2,3]ꢀWittigꢀStill rearrangements are limited. Examples of introducing a hydroxymethyl group at a
quaternary center using a [2,3]ꢀWittigꢀStill rearrangement in the context of natural products synthesis are found in
the structures of punctatin A,11 cobyric acid,12 retigeranic acid A,13 anisatin14 and maoecrystal V.15 These reactions
were achieved to various degrees of efficiency, depending on the structure at hand.16
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We report herein a study involving the [2,3]ꢀWittig and the [2,3]ꢀWittigꢀStill rearrangements of model 3ꢀsubstituted
2ꢀcyclohexenol and 2ꢀcyclopentenol 1ꢀethers. In Scheme 1, we show the theoretically possible transposition
products from allyl ether carbanion (1) and the anionic organolithium ether species (6) derived from the
corresponding tributylstannylmethyl ether. In principle, [2,3]ꢀ and [4,3]ꢀshifts from the allylic ether carbanion (1)
would lead to the desired quaternary carbon centered substituents as in 4 and 5 (Scheme 1A). Undesired [1,2]ꢀ and
[1,4]ꢀshifts would simply introduce a threeꢀcarbon appendage at the original cyclohexyl ether carbon atom as in 2
and 3. In the case of the lithium anion (6) derived from the corresponding tributylstannylmethyl ether via
transmetallation (Scheme 1B), the desired compound 8 would result via a [2,3]ꢀshift, while a [1,2]ꢀshift would lead
to compound 7. A hitherto undocumented alternative “demethylstannylation” pathway could lead to the starting
alcohol (9) via an αꢀelimination mechanism.17
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Scheme 1. Possible products from rearrangement of 1 and 6
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Treatment of the allyl ether 1018 under standard conditions cleanly led to the products 11 and 12 resulting from
[1,2]ꢀ and [1,4]ꢀshifts in 45% and 12% yields, respectively (Scheme 2). The same reaction with the extended diene
allyl ether 13 led to the products 14 and 15 in 45% and 17% yields, respectively. None of the expected [2,3]ꢀ
rearrangement products corresponding to 5 were observed in either case.
Scheme 2. [1,2]ꢀ and [1,4]ꢀRearrangement products observed from allyl ethers 10 and 13
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We then turned our attention to the [2,3]ꢀWittigꢀStill rearrangement. Formation of the lithium anion from 16 in THF
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at ꢀ78 C led, surprisingly, only to the ether cleavage product 19 (35%) (Table 1). Interestingly, the nature of the
base had no significant influence on the outcome of the reaction (Table 1, entries 1ꢀ3). However, a profound
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temperature effect was observed in going from ꢀ78 C to 0 C, affording variable yields of the desired 17,19 in
addition to 1820 and 19 as significant byꢀproducts (Table 1, entries 4ꢀ8). An optimal yield of 17 (48%) was achieved
at ꢀ20 oC, showing a stronger propensity of the [2,3]ꢀrearranged product 17 to form at higher temperatures, whereas
the ether cleavage product 19 is formed at lower temperatures.
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Notably, maintaining the reaction temperature at ꢀ78 C for 4 h, then at 0 C for 1 h, afforded 17 (22%), 18 (13%),
and the ether cleavage product 19 (40%), suggesting that the latter is obtained kinetically (Table 1, entry 8). Lastly, a
change in solvent21 led to a drastic change in the ratio of the products and their yields (Table 1, entries 9ꢀ11).
Quenching the reaction mixture from entry 6 with deuterium oxide led to 17 and 18 with no incorporation of
deuterium on the carbon skeleton.
Table 1. [2,3]ꢀ and [1,2]ꢀRearrangement and cleavage products obtained from the Li anion of 16
OH
O
SnBu3
OH
OH
conditions
+
+
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[2,3]-shift
18
19
[1,2]-shift
entry
conditions
17 (%)a 18 (%)a 19 (%)a
nBuLi, THF, ꢀ78 oC, 4 h
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ꢀ
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ꢀ
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traces
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6
35
10
sBuLi, THF, ꢀ78 oC, 4 h
tBuLi, THF, ꢀ78 oC, 4 h
tBuLi, THF, ꢀ78 oC, then 0 oC, 1 h
nBuLi, THF, ꢀ78 oC, then 0 oC, 1 h
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33
48
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22
18
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48
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29
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12
28
nBuLi, THF, -78 oC, then -20 oC, 8 h
nBuLi, THF, ꢀ78 oC, then ꢀ40 oC, 8 h
nBuLi, THF, ꢀ78 oC (4 h), then 0 oC (1 h)
nBuLi, Et2O, ꢀ78 oC, then ꢀ20 oC, 8 h
nBuLi, THF/HMPA (10:1), ꢀ78 oC, then ꢀ20 oC, 8 h
nBuLi, hexanes, ꢀ78 oC, then ꢀ20 oC, 8 h
10
11
a Isolated yields.
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When the reaction was done with the extended diene 20, only the desired [2,3]ꢀrearranged product 21 (40%) and the
undesired [1,2]ꢀshift product 22 (33%) were formed (Scheme 3A). Surprisingly, the allylic stannylmethyl ether 23
led only to ether cleavage affording the starting cyclopentene 24 in 55% yield. To assess the influence of
conformational restriction and stereochemistry, the synꢀ and antiꢀ diastereomeric stannylmethyl allyl ethers 25 and
28 respectively, were subjected to the optimized WittigꢀStill rearrangement conditions. Only the synꢀdiastereomer 25
led to the [2,3]ꢀrearrangement product 26, albeit in only 17% yield. The major product formed from 25 and 28, as a
result of a [1,2]ꢀrearrangement, was 27 in 73% and 83% yields respectively (Scheme 3A)
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To further probe the influence of geometric constraints, we subjected the stannyl ethers 29 and 30 to rearrangement
(Scheme 3B). We were pleased to find that the expected [2,3]ꢀrearrangement product 33 was formed in 70% yield
from 30, the other product being starting allylic alcohol 34 (5%). The corresponding cyclopentene derivative 29 also
led to the expected [2,3]ꢀrearrangement product 31 accompanied by a regioisomeric byꢀproduct (3: 2, 60%, see
Supporting Information), as well as the ether cleavage product 32 (10%).
Lastly, the exocyclic stannylmethyl allylic ethers 35, 36 and 37 afforded the desired [2,3]ꢀrearrangement products
38,22 39 and 40 as major products in 69%, 60% and 64% yields respectively (Scheme 3C).
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Scheme 3. [2,3]ꢀWittigꢀStill rearrangements and related products
OH
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A.
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SnBu3
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OH
nBuLi, THF
-78 oC, 4 h
+
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21 (40%)
[2,3]-shift
22 (33%)
[1,2]-shift
O
SnBu3
OH
nBuLi, THF
-78 oC to -20 oC
16 h
23
24 (55%)
OH
O
SnBu3
OH
nBuLi, THF
+
-78 oC to -20 oC
16 h
25 (+/-)
26 (17%)
[2,3]-shift
27 (73%)
[1,2]-shift
OH
O
SnBu3
nBuLi, THF
-78 oC to -20 oC
16 h
28 (+/-)
27 (82%)
[1,2]-shift
B.
O
SnBu3
OH
OH
nBuLi, THF
-78 oC to -20 oC,
+
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n
n
16 h
31, n = 1 (60%) 32
33, n = 2 (70%) 34, n = 2 (5%)
[2,3]-shift
, n = 1 (10%)
29, n = 1
30, n = 2
C.
O
OH
nBuLi, THF
-78 oC to -20 oC,
SnBu3
6 h
n
n
38, n = 1 (60%)
39, n = 2 (69%)
40, n = 3 (64%)
[2,3]-shift
35, n = 1
36, n = 2
37, n = 3
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It is well known that bond reorganization in the [2,3]ꢀWittig rearrangement involves a sixꢀelectrons fiveꢀmembered
cyclic transition state in which the allylic oxycarbanion is the migrating entity.23 This thermally allowed concerted
process is favored when the energy gap between the HOMO of the attacking allylic anion and the LUMO of the
“receiving” allylic partner is small. The competing [1,2]ꢀprocess is nonꢀconcerted and believed to proceed by a
radical pair dissociationꢀrecombination mechanism that is favored at higher temperatures. In spite of many
applications of the [2,3]ꢀWittig rearrangement in the transposition of an allyl group in unsaturated cyclic systems,
the results can be dramatically different depending on the nature of the substrate.24
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Our results shown in Scheme 2 are of interest since they extend the original study by Nakai and coworkers to the
prospects of allylic transposition to form a quaternary carbon center in substituted cyclic systems. Since no [2,3]ꢀ
rearrangement product was observed, the activation barrier of the stepwise radical dissociationꢀrecombination
pathway dominates over the concerted process, leading to the [1,2]ꢀrearrangement products 11 and 14 in
preponderance.
In contrast to the results of [2,3]ꢀWittig allylic transpositions of Nakai and coworkers, Still and Mitra had reported
that the [2,3]ꢀrearrangement of the tributylstannylmethyl ether of 1ꢀcyclohexenꢀ2ꢀol via transmetallation with BuLi
(compound 6, R = H, Scheme 1) led to the expected 1ꢀhydroxymethylꢀ2ꢀcyclohexene (compound 8, R = H, Scheme
1) in 95% yield. However, extension to the tributylstannylmethyl ether of cyclodecenꢀ2ꢀol to generate an angular
quaternary center led to mixtures of [1,2]ꢀ and [2,3]ꢀrearrangement products in unspecified low yields. It is therefore
of interest that the tributylstannyl ethers 16 and 20 afforded the [2,3]ꢀrearranged products 17 and 21 containing a
quaternary carbon in 48% and 40% yields respectively, although significant amounts of the [1,2]ꢀrearranged
products 18 and 22 are also formed. Thus, the activation energy barrier difference between the concerted and radical
dissociationꢀrecombination pathways may not be significant in these cases. Furthermore, the trajectory of anionic
attack may be geometrically more favorable compared to the expected [2,3]ꢀWittig rearrangement pathway. Possible
reactive intermediates are shown in Scheme 4.
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For the [1,2]ꢀWittig rearrangement to occur, the radicals formed from the carbanion terminus and/or the migrating
moiety must be stabilized.25 In the case of 16 and 20, only the 3ꢀsubstituted cyclohexenyl radical is stabilized, while
the CH2OLi radical is not (Scheme 4A). This results in the [2,3]ꢀWittigꢀStill products 17 and 21 to predominate over
the [1,2]ꢀWittig products 18 and 22 (Table 1, Schemes 3 and 4A). When the conformation is locked into the
appropriate halfꢀchair, as for synꢀether 25, the rearrangement seems to be slightly more favorable compared to 28
where only the [1,2]ꢀrearrangement product 27 is formed (Scheme 3B). Furthermore, both substrates 25 and 28 lead
to one and the same product 27, further validating the radical dissociationꢀrecombination mechanism. When the
geometric constraints are minimized as in the case of the extended stannylmethyl allyl ethers 29, 30, 35, 36 and 37,
the desired [2,3]ꢀrearrangement products predominate (Scheme 3). Evidently, the energy barrier for the [2,3]ꢀ
rearrangement is more favorable in these extended ethers, since the anion is geometrically better oriented in the
same plane as the olefin to interact with the π* orbital at the methylꢀbearing olefinic terminus.
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Scheme 4. A. Possible mechanisms accounting for [2,3]ꢀ and [1,2]ꢀrearrangement products from lithium carbanions of 16, 20 and
30
The formation of variable amounts of allylic alcohols, either as the kinetic product 19 (Table 1, entries 1ꢀ3) or as the
only isolable product in the attempted [2,3]ꢀWittigꢀStill rearrangements of 16 and 23, is of interest. We are unaware
of related apparent “demethylstannylations” of allylic ethers in such anionic rearrangements of stannylmethyl allyl
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ethers. In order to test the generality of this reaction, we treated simple tributylstannyl ethers 41,26 42 and 4327 with
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nBuLi in THF at ꢀ78 C under the same conditions of the original [2,3]ꢀWittigꢀStill rearrangement. The starting
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alcohols (not shown) were isolated in 71%, 78% and 54% yields respectively, along with Bu4Sn (Scheme 5). It is
well known that the Bu3Sn group does not acidify the αꢀprotons in such stannylmethyl ethers, and that an
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organotin/organolithium exchange (transmetallation) is a fast process at ꢀ78 C. Thus, demethylstannylation takes
place in favor of other pathways at such temperatures (Table 1, entries 1ꢀ3). The reaction may proceed via an αꢀ
elimination to form a carbene and the Li alkoxide.
Scheme 5. Facile “demethylstannylation” of unactivated stannylmethyl ethers
We have studied the prospects of generating a quaternary carbon center in 3ꢀsubstitutedꢀ1ꢀcyclohexꢀ2ꢀeneꢀ1ꢀol allyl
and tributylstannylmethyl ethers via rearrangements of their respective lithium carbanions. In the case of Wittig
allylic transpositions, the major product arises from [1,2]ꢀrearrangement. The desired [2,3]ꢀtransposition competes
effectively with the [1,2]ꢀshift in the WittigꢀStill rearrangement depending on the substrate. When the nucleophilic
carbon atom in the Liꢀanion is in the same plane as the olefin, facile [2,3]ꢀrearrangement takes place. A radical
dissociationꢀrecombination process can prevail when the two moieties are stabilized, leading to [1,2]ꢀrearrangement.
Otherwise, the product distribution will depend on the nature of the substrate, the geometric constraints, and the
temperature. Demethylstannylation of stannylmethyl allyl ethers during [2,3]ꢀWittigꢀStill rearrangements can
predominate especially at low temperature. The products containing a hydroxymethyl group on a quaternary carbon
atom in the model cycloalkene systems described herein could find applications in the synthesis of densely
functionalized natural products of interest, while being cognizant of potential byꢀproducts.
EXPERIMENTAL SECTION
(±)-1-(3-Methylcyclohex-2-enyl)prop-2-en-1-ol (11) and (±)-3-(3-methylcyclohex-2-enyl)propanal (12). A
solution of the bisꢀallylether 10 (40 mg, 0.263 mmol) in dry THF (1.5 mL) was cooled to ꢀ78 oC, maintained under
argon and slowly treated with nBuLi (2.5 M in hexanes, 125 ꢁL, 0.316 mmol). The reaction mixture was stirred as
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such for 4 h, after which an aqueous saturated solution of NH4Cl (5 mL) was added, and the mixture was allowed to
warm up to r.t. The biphasic mixture was separated and the aqueous phase was extracted with Et2O (3 × 5 mL). The
solvent was removed under reduced pressure without heating. Purification of the residue by flash chromatography
(hexanes/Et2O = 100/0 to 90/10) gave a mixture of the [1,2]ꢀrearrangement product 11 (15 mg, 45%) and the [1,4]ꢀ
rearrangement product 12 (4 mg, 12%), both as colorless oils. A minor impurity could not be separated from 12.
[1,2]ꢀRearrangement product (11): IR (neat): νmax = 3329, 2925, 2857, 1448, 916 cm−1; 1H NMR (400 MHz, CDCl3):
δ = 5.96 – 5.86 (1H, m), 5.42 (1H, brs), 5.28 (1H, d, J = 17.2 Hz), 5.19 (1H, d, J = 10.5 Hz), 3.99 (1H, brs), 2.27
(1H, brs), 2.00 – 1.84 (2H, m), 1.84 – 1.70 (2H, m), 1.71 (3H, s), 1.66 – 1.48 (2H, m), 1.43 – 1.30 (1H, m); 13C
NMR (100 MHz, CDCl3): δ = 139.7, 137.4, 119.8, 114.6, 76.0, 41.0, 29.8, 25.1, 23.8, 21.6; HRMS (ESIMS): calcd
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for C10H17O [M+H]+ 153.1274, found 153.1269. [1,4]ꢀRearrangement product (12): H NMR (400 MHz, CDCl3): δ
= 9.80 (1H, s), 5.26 (1H, s), 2.50 (2H, t, J = 1.8 Hz), 2.08 (1H, brs), 2.01 – 1.82 (2H, m), 1.79 – 1.71 (2H, m), 1.69 –
1.52 (3H, m), 1.67 (3H, s), 1.16 – 1.09 (1H, m); 13C NMR (100 MHz, CDCl3): δ = 202.6, 134.7, 124.5, 41.1, 34.4,
29.8, 28.2, 28.1, 23.5, 21.0; HRMS (ESIMS): calcd for C10H16ONa [M+Na]+ 175.1093, found 175.1100.
(±)-(E)-3-(Prop-1-enyl)cyclohex-2-enol. A solution of the commercially available cyclohexedione (200 mg, 1.470
mmol) in CH2Cl2: MeOH (1: 1, 10 mL) was cooled to 0 oC and CeCl3ꢂ7H2O (725 mg, 0.294 mmol), and NaBH4 (67
mg, 1.763 mmol) were added in portions. After stirring for two hours, an aqueous saturated solution of NH4Cl (15
mL) was added to the mixture, the biphasic mixture was separated and the aqueous phase was extracted with CH2Cl2
(3 × 10 mL). The solvent was removed under reduced pressure without heating. Purification of the residue by flash
chromatography (hexanes/Et2O = 80/20) gave the title allylic alcohol (160 mg, 79%) as a colorless light oil. IR
(neat): νmax = 3294, 2930, 2860, 1448, 1034, 962 cm−1; 1H NMR (400 MHz, CDCl3): δ = 6.03 (1H, d, J = 15.6 Hz),
5.76 – 5.63 (1H, m), 5.61 (1H, s), 4.26 (1H, s), 2.20 – 2.01 (3H, m), 1.84 – 1.76 (2H, m), 1.76 (3H, d, J = 6.5 Hz),
1.65 – 1.48 (2H, m); 13C NMR (100 MHz, CDCl3): δ = 138.0, 133.4, 127.8, 124.1, 65.8, 31.7, 24.1, 18.6, 17.9;
HRMS (ESIMS): calcd for C9H14ONa [M+Na]+ 161.0937, found 161.0939.
(±)-(E)-3-(Allyloxy)-1-(prop-1-enyl)cyclohex-1-ene (13). A solution of (E)ꢀ3ꢀ(propꢀ1ꢀenyl)cyclohexꢀ2ꢀenol (75
o
mg, 0.543 mmol) in THF (3 mL) was cooled to 0 C and treated with KHMDS (0.5 M in toluene, 130 ꢁL, 0.652
mmol) under argon. After five minutes, allyl iodide (75 ꢁL, 0.815 mmol) was added at the same temperature and the
mixture was allowed to stir as such for two hours. The reaction mixture was quenched at 0 °C with a saturated
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solution of NH4Cl (5 mL). The biphasic mixture was separated and the aqueous phase was extracted with Et2O (3 ×
20 mL). The solvent was removed under reduced pressure without heating. Purification of the residue by flash
chromatography (hexanes/Et2O = 100/0 to 95/5) gave the title compound (65 mg, 71%) as a colorless light oil. Rf =
1
0.6 (hexanes/EtOAc = 95/5) [KMnO4]. IR (neat): νmax = 2930, 1645, 1374, 1339, 1076 cm−1; H NMR (400 MHz,
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CDCl3): δ = 6.05 (1H, d, J = 17.4 Hz), 6.00 – 5.85 (1H, m), 5.73 – 5.65 (2H, m), 5.28 (1H, d, J = 17.2 Hz), 5.14
(1H, d, J = 10.3 Hz), 4.05 – 3.96 (3H, m), 2.19 – 2.04 (2H, m), 1.86 – 1.75 (2H, m), 1.76 (3H, d, J = 6.4 Hz), 1.66 –
1.51 (2H, m); 13C NMR (100 MHz, CDCl3): δ = 138.8, 135.5, 133.9, 126.0, 124.2, 116.5, 73.0, 69.1, 28.6, 24.7,
19.3, 18.3; HRMS (ESIMS) could not be done due to the volatility of the product.
(±)-(E)-1-(3-(Prop-1-enyl)cyclohex-2-enyl)prop-2-en-1-ol (14) and (±)-(E)-3-(3-(prop-1-enyl)cyclohex-2-
enyl)propanal (15). Obtained from the bisꢀallylether 13 (30 mg, 0.169 mmol) using the same procedure as for
compounds 11 and 12. Purification of the residue by flash chromatography (hexanes/Et2O = 100/0 to 90/10) gave a
mixture of the [1,2]ꢀrearrangement product 14 (14 mg, 45%) and the [1,4]ꢀrearrangement product 15 (5 mg, 17%) as
colorless oils. A minor impurity could not be separated from 15. [1,2]ꢀRearrangement product (14): IR (neat): νmax
=
3359, 2928, 2858, 1447, 963 cm−1; 1H NMR (400 MHz, CDCl3): δ = 6.10 (1H, d, J = 15.4 Hz), 5.95 – 5.86 (1H, m),
5.69 – 5.60 (2H, m), 5.28 (1H, d, J = 17.2 Hz), 5.19 (1H, d, J = 10.5 Hz), 4.01 (1H, brs), 2.42 – 2.34 (1H, m), 2.24 –
2.00 (2H, m), 1.95 – 1.80 (1H, m), 1.77 (3H, d, J = 6.3 Hz), 1.66 – 1.48 (2H, m), 1.43 – 1.25 (2H, m); 13C NMR
(100 MHz, CDCl3): δ = 139.8, 138.4, 134.5, 125.6, 122.5, 115.3, 76.4, 41.9, 25.6, 24.7, 21.6, 18.2; HRMS (ESIMS):
calcd for C12H18ONa [M+Na]+ 201.1250, found 201.1244. [1,4]ꢀRearrangement product (15): IR (neat): νmax = 2927,
1
2856, 1724, 1447, 963 cm−1; H NMR (400 MHz, CDCl3): δ = 9.81 (1H, s), 6.05 (1H, d, J = 15.2 Hz), 5.53 – 5.54
(1H, m), 5.47 (1H, s), 2.50 (2H, t, J = 1.8 Hz), 2.24 – 2.01 (3H, m), 1.82 – 1.47 (6H, m), 1.76 (3H, d, J = 6.5 Hz);
13C NMR (100 MHz, CDCl3): δ = 202.4, 136.0, 134.0, 129.6, 122.0, 41.0, 34.8, 28.4, 27.8, 24.3, 21.0, 17.9; HRMS
(ESIMS): calcd for C12H19O [M+H]+ 179.1430, found 179.1422.
(±)-syn-4-(tert-Butyl)-3-methylcyclohex-2-enol and (±)-anti-4-(tert-butyl)-3-methylcyclohex-2-enol. A solution
of the known 4ꢀ(tertꢀbutyl)ꢀcyclohexꢀ2ꢀenone28 (500 mg, 3.29 mmol) in dry Et2O (13 mL) was cooled to ꢀ78 oC and
o
treated with MeLi (1.6 M in Et2O, 8.12 mL). Then, the mixture was warmed up to 0 C and MeLi (1.6 M in Et2O,
8.12 mL) was added again. The solution was stirred as such for 10 min, after which a solution of the known 4ꢀ(tertꢀ
butyl)ꢀcyclohexꢀ2ꢀenone (500 mg, 3.29 mmol) in dry Et2O (1 mL) was slowly added and the mixture was stirred for
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2 h. Then, TEA (0.915 mL, 6.57 mmol) and TMSCl (0.830 mL, 6.57 mmol) were added and the mixture was stirred
for 2 h while allowing to warm up to r.t. The reaction was then quenched with H2O (20 mL) and the aqueous phase
was extracted with hexanes (3 × 10 mL). The combined organic phases were dried over Na2SO4, then concentrated
under reduced pressure. Without further purification, the crude silylenolether was dissolved in MeCN (15 mL) and
Pd(OAc)2 (1.05 eq.) was added at r.t. The reaction mixture was stirred for 16 h, then filtered on Celite and the
solvent was removed under reduced pressure. The residue was purified by flash chromatography (hexanes/EtOAc =
80/20) to give the known 4ꢀ(tertꢀbutyl)ꢀ3ꢀmethylꢀcyclohexꢀ2ꢀenone29 (410 mg, 83%). The latter enone (370 mg,
2.43 mmol) was subjected to the reduction conditions used for preparing (±)ꢀ(E)ꢀ3ꢀ(Propꢀ1ꢀenyl)cyclohexꢀ2ꢀenol.
The residue was purified by flash chromatography (hexanes/EtOAc = 100/0 to 90/10) to give the two titles alcohols
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(360 mg, d.r. = 3: 2, 96%) as separable colorless oils. synꢀ4ꢀ(tertꢀButyl)ꢀ3ꢀmethylcyclohexꢀ2ꢀenol: IR (neat): νmax
=
3319, 2946, 2868, 1441, 1367, 1275, 1198, 1138, 1084, 987 cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.64 (1H, brs),
4.18 (1H, m), 1.88 – 1.77 (2H, m), 1.86 (3H, s), 1.72 – 1.63 (4H, m), 1.04 (9H, s); 13C NMR (100 MHz, CDCl3): δ =
141.5, 128.3, 86.0, 48.1, 33.5, 30.2, 29.9, 26.8, 23.1; HRMS (ESIMS): calcd for C11H20ONa [M+Na]+ 191.1406,
found 191.1398. antiꢀ4ꢀ(tertꢀButyl)ꢀ3ꢀmethylcyclohexꢀ2ꢀenol: IR (neat): νmax = 3323, 2950, 2864, 1445, 1367, 1276,
1
1220, 1171, 1132, 1004 cm−1; H NMR (400 MHz, CDCl3): δ = 5.56 (1H, brs), 4.08 (1H, brs), 2.03 – 1.97 (2H, m),
1.88 – 1.83 (1H, m), 1.86 (3H, s), 1.78 – 1.70 (1H, m), 1.55 – 1.45 (1H, m), 1.42 – 1.33 (1H, m), 0.96 (9H, s);13C
NMR (100 MHz, CDCl3): δ = 139.3, 130.2, 86.4, 48.2, 34.1, 31.4, 29.7, 26.8, 23.1; HRMS (ESIMS): calcd for
C11H20ONa [M+Na]+ 191.1406, found 191.1398.
Typical Procedure for the synthesis of 16, 20, 23, 25, 28, 29, 30, 35, 36, 37 and 42
A solution of the starting alcohol (1 eq.) in dry THF (0.2 M) was slowly added to a suspension of KH in mineral oil
o
(30%, 1 mL) at r.t. under argon. After stirring for 2 h at r.t., the suspension was cooled to 0 C and quenched very
carefully with water (10 mL). The organic and aqueous phases were then separated, and the aqueous phase was
extracted with Et2O (3 × 10 mL). The combined organic layers were then dried over Na2SO4, and the solvent was
removed under reduced pressure.
(±)ꢀTributyl ((3-methylcyclohex-2-enyloxy)methyl)stannane (16). Obtained from 3ꢀmethylcyclohexꢀ2ꢀenol (100
mg, 0.892 mmol) using the general procedure. The residue was purified by flash chromatography (hexanes/EtOAc =
100/0 to 97.5/2.5) to give the stannane 16 (250 mg, 68%) as a light colorless liquid. IR (neat): νmax = 2923, 2853,
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1454, 1059 cm−1; H NMR (400 MHz, CDCl3): δ = 5.54 (1H, brs), 3.83 (1H, d, J = 10.0 Hz), 3.75 (1H, d, J = 10.0
Hz), 3.59 (1H, brs), 1.99 – 1.82 (2H, m), 1.77 – 1.67 (1H, m), 1.69 (3H, s), 1.65 – 1.42 (8H, m), 1.39 – 1.27 (6H,
m), 1.01 – 0.83 (16H, m); 13C NMR (100 MHz, CDCl3): δ = 137.7, 122.2, 58.2, 30.0, 28.8, 27.1, 26.9, 26.5, 23.4,
19.1, 13.3, 8.6; HRMS (ESIMS): calcd for C20H40OSnNa [M+Na]+ 439.1993, found 439.1997.
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(±)-(E)-Tributyl ((3-(prop-1-enyl)cyclohex-2-enyloxy)methyl)stannane (20). Obtained from (±)ꢀ(E)ꢀ3ꢀ(propꢀ1ꢀ
enyl)cyclohexꢀ2ꢀenol (±) (85 mg, 0.616 mmol) using the general procedure. The residue was purified by flash
chromatography (hexanes 100%) to give the stannane 20 (120 mg, 44%) as a light colorless liquid. IR (neat): νmax
=
2922, 2852, 1455, 1068, 962 cm−1; 1H NMR (400 MHz, CDCl3): δ = 6.08 (1H, d, J = 15.7 Hz), 5.73 – 5.66 (2H, m),
3.85 (1H, d, J = 10.0 Hz), 3.76 (1H, d, J = 10.0 Hz), 3.72 (1H, brs), 2.16 – 2.02 (2H, m), 1.88 – 1.79 (2H, m), 1.80
(3H, d, J = 6.4 Hz), 1.62 – 1.46 (8H, m), 1.41 – 1.27 (6H, m), 1.01 – 0.80 (15H, m); 13C NMR (100 MHz, CDCl3): δ
= 137.8, 133.8, 126.3, 123.5, 77.6, 58.3, 28.8, 27.6, 26.9, 24.4, 19.0, 17.9, 13.4, 8.6; HRMS (ESIMS): calcd for
C22H43OSn [M+H]+ 443.2336, found 443.2330.
(±)-Tributyl ((3-methylcyclopent-2-enyloxy)methyl)stannane (23). Obtained from 3ꢀmethylcyclopentꢀ2ꢀenol (100
mg, 0.0.892 mmol) using the general procedure. The residue was purified by flash chromatography (hexanes/EtOAc
= 100/0 to 92/8) to give the stannane 23 (300 mg, 84%) as a light colorless liquid. IR (neat): νmax = 2962, 2925,
1458, 1379, 1350, 1157, 1055 cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.49 (1H, s), 4.29 (1H, brs), 3.72 (1H, d, J =
10.5 Hz), 3.66 (1H, d, J = 10.5 Hz), 2.43 – 2.29 (1H, m), 2.20 – 2.05 (2H, m), 1.83 – 1.71 (1H, m), 1.77 (3H, s),
1.61 – 1.39 (6H, m), 1.30 (6H, m), 0.98 – 0.80 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 145.7, 125.3, 88.8, 58.5,
35.3, 30.3, 29.1, 27.3, 16.9, 13.7, 9.0; HRMS (ESIMS): calcd for C19H38ONaSn [M+Na]+, 425.1837 found
425.1838.
(±)-Tributyl (((syn-4-(tert-butyl)-3-methylcyclohex-2-en-1-yl)oxy)methyl)stannane (25). Obtained from synꢀ4ꢀ
(tertꢀbutyl)ꢀ3ꢀmethylcyclohexꢀ2ꢀenol (150 mg, 0.893 mmol) described above, using the general procedure. The
residue was purified by flash chromatography (hexanes/EtOAc = 100/0 to 95/5) to give the stannane 25 (361 mg,
1
86%) as a light colorless liquid. IR (neat): νmax = 2956, 2867, 1460, 1372, 1196, 1084, 1044, 924 cm−1; H NMR
(400 MHz, CDCl3): δ = 5.63 (1H, brs), 3.84 (1H, d, J = 12.0 Hz), 3.76 (1H, d, J = 12.0 Hz), 3.51 (1H, m), 2.04 –
1.96 (1H, m), 1.94 – 1.88 (1H, m), 1.85 (3H, s), 1.80 – 1.73 (1H, m), 1.59 – 1.50 (6H, m), 1.38 – 1.30 (8H, m), 0.98
(9H, s), 0.96 – 0.90 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 138.6, 128.7, 55.6, 48.6, 34.1, 31.6, 29.5, 29.2,
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27.5, 27.3, 26.7, 23.4, 22.7, 14.1, 13.7, 9.0; HRMS (ESIMS): calcd for C24H48ONaSn [M+Na]+, 495.2624 found
495.2616.
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(±)-Tributyl (((anti-4-(tert-butyl)-3-methylcyclohex-2-en-1-yl)oxy)methyl)stannane (28). Obtained from antiꢀ4ꢀ
(tertꢀbutyl)ꢀ3ꢀmethylcyclohexꢀ2ꢀenol (100 mg, 0.595 mmol) described above, using the general procedure. The
residue was purified by flash chromatography (hexanes/EtOAc = 100/0 to 95/5) to give the stannane 28 (208 mg,
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74%) as a light colorless liquid. IR (neat): νmax = 2954, 2921, 2850, 1717, 1457, 1346, 1173, 1048, 957 cm−1; H
NMR (400 MHz, CDCl3): δ = 5.68 (1H, brs), 3.80 (1H, d, J = 12.0 Hz), 3.75 (1H, d, J = 12.0 Hz), 3.60 (1H, m),
1.88 – 1.83 (1H, m), 1.86 (3H, s), 1.80 – 1.69 (2H, m), 1.59 – 1.51 (6H, m), 1.38 – 1.28 (8H, m), 1.03 (9H, s), 0.96 –
0.92 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 140.8, 126.6, 58.2, 48.4, 33.7, 31.6, 30.2, 29.2, 27.3, 27.0, 26.1,
23.4, 22.7; HRMS (ESIMS): calcd for C24H48ONaSn [M+Na]+, 495.2624 found 495.2622.
(±)-Tributyl (((2-methylcyclopent-1-enyl)methoxy)methyl)stannane (29). Obtained from the known (2ꢀ
methylcyclopentꢀ1ꢀenyl)methanol30 (100 mg, 0.892 mmol) using the general procedure. The residue was purified by
flash chromatography (hexanes/EtOAc = 100/0 to 94/6) to give the stannane 29 (180 mg, 70%) as a light colorless
liquid. IR (neat): νmax = 2961, 2925, 2850, 1466, 1379, 1050, 876 cm−1; 1H NMR (400 MHz, CDCl3): δ = 3.90 (2H,
s), 3.71 – 3.62 (2H, m), 2.42 – 2.26 (4H, m), 1.84 – 1.73 (2H, m), 1.68 (3H, s), 1.60 – 1.41 (6H, m), 1.30 (6H, sept, J
= 7.3 Hz), 0.97 – 0.79 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 136.2, 132.4, 71.3, 60.7, 38.8, 34.6, 29.1, 27.3,
21.6, 13.9, 13.7, 8.9; HRMS (ESIMS): calcd for C20H40ONaSn [M+Na]+, 439.1993 found 439.1991.
(±)-Tributyl (((2-methylcyclohex-1-enyl)methoxy)methyl)stannane (30). Obtained from the known (2ꢀ
methylcyclohexꢀ1ꢀenyl)methanol30 (100 mg, 0.892 mmol) using the general procedure. The residue was purified by
flash chromatography (hexanes/EtOAc = 100/0 to 94/6) to give the stannane 30 (320 mg, 94%) as a light colorless
1
liquid. IR (neat): νmax = 2961, 2928, 2861, 2346, 1460, 1379, 1251, 1140, 1052, 875 cm−1; H NMR (400 MHz,
CDCl3): δ = 3.83 (2H, s), 3.68 (2H, m), 2.03 – 1.94 (4H, m), 1.67 (3H, s), 1.62 – 1.56 (4H, m), 1.54 – 1.46 (6H, m),
1.30 (6H, sept, J = 7.3 Hz), 1.00 – 0.80 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 132.1, 127.6, 74.9, 60.8, 32.0,
29.2, 27.6, 27.3, 23.1, 19.1, 13.7, 8.9; HRMS (ESIMS): calcd for C21H42ONaSn [M+Na]+ 453.2150, found
453.2156.
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Tributyl
((2-cyclopentylideneethoxy)methyl)stannane
(35).
Obtained
from
the
known
2ꢀ
cyclopentylideneethanol32 (150 mg, 1.34 mmol) using the general procedure. The residue was purified by flash
chromatography (hexanes/EtOAc = 100/0 to 96/4) to give the stannane 35 (400 mg, 72%) as a light colorless liquid.
IR (neat): νmax = 2954, 2921, 2850, 1717, 1457, 1346, 1173, 1048, 957 cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.47
– 5.41 (1H, m), 3.86 (2H, d, J = 6.2 Hz), 3.76 – 3.72 (2H, m), 2.34 – 2.22 (4H, m), 1.74 – 1.57 (4H, m), 1.58 – 1.49
(7H, m), 1.39 – 1.26 (7H, m), 0.97 – 0.79 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 147.6, 117.1, 73.0, 61.2,
33.7, 29.1, 28.8, 27.3, 26.3, 26.1, 13.7, 9.0; HRMS (ESIMS): calcd for C20H40ONaSn [M+Na]+, 439.1993 found
439.1981.
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Tributyl ((2-cyclohexylideneethoxy)methyl)stannane (36). Obtained from the known 2ꢀcyclohexylideneethanol32
(160 mg, 1.27 mmol) using the general procedure. The residue was purified by flash chromatography
(hexanes/EtOAc = 100/0 to 96/4) to give the stannane 36 (350 mg, 64%) as a light colorless liquid. IR (neat): νmax
=
2922, 2849, 1453, 1047, 866 cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.31 – 5.24 (1H, m), 3.88 (2H, d, J = 6.2 Hz),
3.76 – 3.72 (2H, m), 2.22 – 2.18 (2H, m), 2.16 – 2.12 (2H, m), 1.59 – 1.46 (11H, m), 1.32 – 1.26 (7H, m), 0.97 –
0.79 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 144.3, 118.2, 70.6, 61.0, 37.1, 29.1, 29.1, 28.5, 27.8, 27.3, 26.7,
13.7, 9.0; HRMS (ESIMS): calcd for C21H42ONaSn [M+Na]+, 453.2150 found 453.2142.
Tributyl
((2-cycloheptylideneethoxy)methyl)stannane
(37).
Obtained
from
the
known
2ꢀ
cycloheptylideneethanol33 (170 mg, 1.21 mmol) using the general procedure. The residue was purified by flash
chromatography (hexanes/EtOAc = 100/0 to 98/2) to give the stannane 37 (380 mg, 71%) as a light colorless liquid.
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IR (neat): νmax = 2919, 2850, 1454, 1377, 1059, 869 cm−1; H NMR (400 MHz, CDCl3): δ = 5.35 – 5.27 (1H, m),
3.86 (2H, d, J = 5.6 Hz), 3.76 – 3.72 (2H, m), 2.28 – 2.22 (4H, m), 1.63 – 1.44 (14H, m), 1.35 – 1.25 (6H, m), 0.95
– 0.84 (15H, m); 13C NMR (100 MHz, CDCl3): δ = 145.4, 122.0, 71.4, 61.2, 37.7, 30.2, 29.8, 29.1, 29.0, 28.9, 27.3,
27.2, 13.7, 9.0; HRMS (ESIMS) could not be done.
Tributyl (phenethoxymethyl)stannane (42). Obtained from phenethyl alcohol (136 mg, 1.12 mmol) using the
general procedure. The residue was purified by flash chromatography (hexanes/EtOAc = 100/0 to 97.5/2.5) to give
1
the stannane 42 (365 mg, 77%) as a light colorless liquid. IR (neat): νmax = 2954, 2921, 2851, 1454, 1080 cm−1; H
NMR (400 MHz, CDCl3): δ = 7.35 – 7.25 (5H, m), 3.81 (2H, s), 3.60 (2H, t, J = 7.0 Hz), 2.92 (2H, t, J = 7.0 Hz),
1.67 – 1.44 (6H, m), 1.40 – 1.34 (9H, m), 0.98 – 0.93 (12H, m); 13C NMR (100 MHz, CDCl3): δ = 139.5, 129.0,
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128.2, 126.0, 76.3, 62.0, 36.4, 29.2, 27.4,13.7, 9.0; HRMS (ESIMS): calcd for C21H38OSnNa [M+Na]+ 449.1837,
found 449.1833.
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Typical Procedure for the Wittig-Still rearrangement from the stannyl ethers 20, 25, 28, 29, 30, 35, 36 and 37.
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A solution of the starting stannyl ether (1 eq.) in dry THF (0.2 M) was cooled to ꢀ78 C and slowly treated with
nBuLi (2.5 M in hexanes, 1.05 eq.). The reaction mixture was stirred as such for 20 min, after which it was
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transferred to a ꢀ20 C cooling bath (unless otherwise stated) and stirred for the indicated time. Then, the reaction
was quenched upon addition of an aqueous saturated solution of NH4Cl, and the mixture was allowed to warm up to
r.t. The biphasic mixture was separated and the aqueous phase was extracted with Et2O (3 × 5 mL).
(±)-(E)-(1-(Prop-1-enyl)cyclohex-2-enyl)methanol (21) and (±)-(E)-(3-(prop-1-enyl)cyclohex-2-enyl)methanol
(22). Obtained from the tin ether 20 (90 mg, 0.204 mmol) using the general procedure. Purification of the residue by
flash chromatography (hexanes/Et2O = 100/0 to 90/10) gave a mixture of the [2,3]ꢀrearrangement product 21 (12
mg, 40%) and the [1,2]ꢀrearrangement product 22 (10 mg, 33%), both as colorless oils. [2,3]ꢀRearrangement product
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(21): IR (neat): νmax = 3294, 2930, 1447, 1032, 970 cm−1; H NMR (400 MHz, CDCl3): δ = 5.89 – 5.80 (1H, m),
5.54 – 5.32 (3H, m), 3.50 – 3.37 (3H, m), 2.02 – 1.97 (1H, m), 1.63 (3H, d, J = 6.8 Hz), 1.59 – 1.49 (5H, m); 13C
NMR (100 MHz, CDCl3): δ = 135.4, 129.4, 129.3, 126.7, 69.6, 43.3, 30.6, 29.8, 25.1, 18.0; HRMS (ESIMS): calcd
for C10H16ONa [M+Na]+ 175.1098, found 175.1104. [1,2]ꢀRearrangement product (22): IR (neat): νmax = 3302,
1
2923, 2856, 1445, 1052, 963, 909 cm−1; H NMR (400 MHz, CDCl3): δ = 6.08 (1H, d, J = 15.7 Hz), 5.72 – 5.61
(1H, m), 5.55 (1H, s), 3.57 (2H, d, J = 6.3 Hz), 2.42 (1H, brs), 2.24 – 2.17 (1H, m), 2.17 – 2.04 (1H, m), 1.86 – 1.73
(2H, m), 1.76 (3H, d, J = 6.5 Hz), 1.64 – 1.55 (1H, m), 1.46 (1H, brs), 1.42 – 1.32 (1H, m); 13C NMR (100 MHz,
CDCl3): δ = 137.9, 134.3, 126.7, 122.6, 61.7, 38.9, 25.6, 24.8, 21.1, 18.2; HRMS (ESIMS): calcd for C10H16ONa
[M+Na]+ 175.1099, found 175.1089.
(±)-(6-(tert-Butyl)-1-methylcyclohex-2-en-1-yl)methanol (26) and (±)-(4-(tert-butyl)-3-methylcyclohex-2-en-1-
yl)methanol (27). Obtained from the tin ether 25 (100 mg, 0.212 mmol) using the general procedure. Purification of
the residue by flash chromatography (hexanes/EtOAc = 100/0 to 80/20) gave a mixture of the [2,3]ꢀrearrangement
product 26 (6 mg, 17%) and the [1,2]ꢀRearrangement product 27 (25 mg, 71 %). [1,2]ꢀRearrangement product (27):
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IR (neat): νmax = 3327, 2946, 2864, 1461, 1367, 1196, 1030 cm−1; H NMR (400 MHz, CDCl3): δ = 5.44 (1H, brs),
3.54 (2H, d, J = 6.2 Hz), 2.34 (1H, brs), 1.95 – 1.84 (2H, m), 1.84 (3H, m), 1.63 – 1.57 (1H, m), 1.52 – 1.43 (2H,
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m), 1.00 (3H, s); 13C NMR (100 MHz, CDCl3) of the mixture: δ = 138.8, 126.1, 66.8, 47.3, 38.6, 33.0, 30.4, 27.0,
25.0, 22.0; HRMS (ESIMS): calcd for C12H22OLi [M+Li]+ 189.1825, found 189.1823. [2,3]ꢀRearrangement product
(26): Rf = 0.25 (15% EtOAc/hexanes), [KMnO4], not seen by UV. IR (neat): νmax = 3415, 2958, 2903, 2836, 1482,
1396, 1367, 1227, 1043, 1004, 892 cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.93 – 5.88 (1H, m), 4.22 (1H, d, J = 5.2
Hz), 3.92 – 3.86 (1H, m), 3.53 – 3.47 (1H, m), 2.15 – 2.07 (1H, m), 2.03 – 1.92 (1H, m), 1.77 – 1.62 (2H, m), 1.36 –
1.33 (1H, m), 1.29 – 1.25 (1H, m), 1.15 (3H, s), 1.07 (9H, s); 13C NMR (100 MHz, CDCl3) of the mixture: δ =
136.5, 128.7, 87.6, 52.8, 42.6, 34.6, 30.1, 28.0, 26.5, 23.3; HRMS (ESIMS): calcd for C12H22ONa [M+Na]+
205.1563, found 205.1567.
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(±)-(1-Methyl-2-methylenecyclopentyl)methanol (31) and (±)-(1,2-dimethylcyclopent-2-en-1-yl)methanol
Obtained from the tin ether 29 (150 mg, 0.361 mmol) using the general procedure. Purification of the residue by
flash chromatography (hexanes/EtOAc = 100/0 to 87/13) gave an unseperable mixture of the [2,3]ꢀrearrangement
product 31 and its regioisomer (3: 2, 27 mg, 60%) as well as 2ꢀmethylcyclopentꢀ1ꢀenyl)methanol 3231 as determined
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by 1H NMR (4 mg, 10 %). IR (neat): νmax = 3352, 2958, 2872, 1653, 1453, 1382, 1043, 1022 cm−1; H NMR (400
MHz, CDCl3): δ = 4.98 (1H, brs), 4.77 (1H, brs), 3.48 (1H, d, J = 7.4 Hz), 3.33 (1H, d, J = 7.4 Hz), 2.46 – 2.29 (2H,
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m), 1.84 – 1.76 (1H, m), 1.69 – 1.55 (3H, m), 1.52 – 1.42 (1H, m), 1.06 (3H, s); H NMR (400 MHz, CDCl3): δ =
5.46 (1H, brs), 3.36 (2H, dd, J = 31.5, 10.8 Hz), 2.27 – 2.21 (2H, m), 2.08 – 2.00 (1H, m), 1.69 – 1.55 (2H, m), 1.61
(3H, s), 0.98 (3H, s); 13C NMR (100 MHz, CDCl3) of the mixture: δ = 158.1, 142.7, 127.1, 105.2, 69.3, 68.7, 51.6,
47.4, 36.9, 34.8, 33.9, 29.6, 23.9, 22.6, 21.5, 12.3; HRMS (ESIMS): calcd for C8H15O [M+H]+ 127.1117, found
127.1119.
(±)-1-Methyl-2-methylenecyclohexanol (33). Obtained from the tin ether 30 (150 mg, 0.349 mmol) using the
general procedure. Purification of the residue by flash chromatography (hexanes/ EtOAc = 100/0 to 88.0/12.0) gave
the [2,3]ꢀrearrangement product 33 (34 mg, 70%) as a colorless oil, as well as 34 (2 mg, 5%). IR (neat): νmax = 3345,
2933, 2863, 1639, 1449, 1050, 1027 cm−1; 1H NMR (400 MHz, CDCl3): δ = 4.89 (1H, s), 4.76 (1H, s), 3.69 (1H, d, J
= 10.6 Hz), 3.42 (1H, d, J = 10.6 Hz), 2.30 – 2.05 (2H, m), 1.73 – 1.48 (4H, m), 1.47 – 1.19 (3H, m), 1.09 (3H, s);
13C NMR (100 MHz, CDCl3): δ = 152.3, 109.0, 67.9, 41.8, 36.4, 33.1, 28.0, 23.4, 22.1; HRMS (ESIMS): calcd for
C9H17O [M+H]+ 141.1274, found 141.1272.
(1-Vinylcyclopentyl)methanol (38). Obtained from the tin ether 35 (200 mg, 0.480 mmol) using the general
procedure. Purification of the residue by flash chromatography (hexanes/EtOAc = 100/0 to 90/10) gave an mixture
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of the [2,3]ꢀrearrangement product 38 (36 mg, 60%). IR (neat): νmax = 3357, 2949, 2866, 1635, 1454, 1040, 1001,
909 cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.83 (1H, dd, J = 17.5, 10.8 Hz), 5.18 (1H, d, J = 10.8 Hz), 5.16 (1H, d,
J = 17.5 Hz), 3.41 (2H, s), 1.66 – 1.50 (13H, m); 13C NMR (100 MHz, CDCl3) δ = 144.3, 113.6, 68.6, 51.5, 33.6,
24.2; HRMS (ESIMS): calcd for C8H14OLi [M+Li]+ 133.1199, found 133.1204.
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(1-Vinylcycloheptyl)methanol (40). Obtained from the tin ether 37 (250 mg, 0.450 mmol) using the general
procedure. Purification of the residue by flash chromatography (hexanes/EtOAc = 100/0 to 90/10) gave a mixture of
the [2,3]ꢀrearrangement product 40 (44 mg, 64%). IR (neat): νmax = 3358, 2916, 2855, 1635, 1459, 1058, 1022, 910
cm−1; 1H NMR (400 MHz, CDCl3): δ = 5.68 (1H, dd, J = 17.7, 10.9 Hz), 5.18 (1H, d, J = 10.9 Hz), 5.06 (1H, d, J =
17.7 Hz), 3.27 (2H, s), 1.63 – 1.41 (13H, m); 13C NMR (100 MHz, CDCl3): δ = 145.3, 114.4, 69.6, 45.6, 34.1, 30.4,
22.6; HRMS (ESIMS): calcd for C10H18OLi [M+Li]+ 161.1512 found 161.1518.
ASSOCIATED CONTENT
Acknowledgments
We acknowledge financial support from NSERC, and FQRNT for a fellowship to SD. We thank the CFI for a
departmental grant.
Supporting Information
1
Copies of the H and 13C NMR spectra of new compounds (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
REFERENCES
(1) (a) For an authoritative monograph, see Quaternary Stereocenters: Challenges and Solutions for Organic
Chemistry; Christoffers, J., Baro, A., Eds.; WileyꢀVCH: Weinheim, 2005; (b) Fuji, K. Chem. Rev. 1993, 93,
2037−2066.
(2) For selected examples, see (a) Corey, E. J.; GuzmanꢀPerez, A. Angew. Chem. Int. Ed. 1998, 37, 388−401; (b)
Denissova, I.; Barriault, L. Tetrahedron, 2003, 59, 10105−10146; (c) Douglas, C. J.; Overman, L. E. Proc.
Nat. Acad. Sci. USA, 2004, 101, 5363−5367; (d) Trost, B. M.; Jiang, C. Synthesis 2006, 369−396.
(3) See for example (a) Martin, C. L.; Overman, L. E. J. Am. Chem. Soc. 2010, 132, 4894−4906; (b) Jones, S. B.;
Simmons, B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2009, 131, 13606−13607; (c) Arineuto, H.; Uemura, D.
in Quaternary Stereocenters: Challenges and Solutions for Organic Chemistry; Christoffers, J., Baro, A.,
Eds.; WileyꢀVCH: Weinheim, 2005, Chapter 1, pp. 1ꢀ24.
(4) (a) Wittig, G.; Döser, H.; Lorenz, I. Liebigs Ann. Chem. 1949, 562, 192−205; (b) Nakai, T.; Mikami, K. Chem.
Rev. 1986, 86, 885−902; (c) Marshall, M. A. in Comprehensive Organic Synthesis, Vol. 3; Trost, B.M.,
18
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3
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7
8
Fleming, I., Eds.; Pergamon: Oxford, 1991, pp. 975−1014; (d) Marshall, M. A. in Comprehensive Organic
Synthesis, Vol. 6; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991, pp. 873−903; (e) Nakai, T.;
Mikami, K. Org. React. 1994, 46, 105−209; (f) Organolithiums: Selectivity for Synthesis; Clayden, J., Ed.;
Pergamon: Oxford, 2002, Chapter 8.
9
(5) (a) Nakai, T.; Mikami, K.; Taya, S.; Fujita, Y. J. Am. Chem. Soc. 1981, 103, 6492−6494; (b) Mikami, K.;
Kimura, Y.; Kishi, N.; Nakai, T. J. Org. Chem. 1983, 48, 279−281; (c) Mikami, K.; Uchida, T.; Hirano, T.;
Wu, Y.ꢀD.; Houk, K. N. Tetrahedron 1994, 50, 5917−5926; (d) Tomooka, K.; Igarashi, T.; Watanabe, M.;
Nakai, T. Tetrahedron 1992, 33, 5795−5798.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) Still, W. C.; Mitra, A. J. Am. Chem. Soc. 1978, 100, 1927−1928.
(7) Still, W. C. J. Am. Chem. Soc. 1978, 100, 1481−1487.
(8) Trost, B. M.; Mao, M. K.ꢀT.; Balkovec, J. M.; Buhlmayer, P. J. Am. Chem. Soc. 1986, 108, 4965−4973.
(9) Castedo, L.; Mascareñas, J. L.; Mourinõ, A. Tetrahedron Lett. 1987, 28, 2099−2102.
(10) Crimmins, M. T.; Gould, L. D. J. Am. Chem. Soc. 1987, 109, 6199−6200.
(11) Sugimura, T.; Paquette, L. A. J. Am. Chem. Soc. 1987, 109, 3017−3024.
(12) Mulzer, J.; Riether, D. Org. Lett. 2000, 2, 3139−3141.
(13) Paquette, L. A.; Wright, J.; Drtina, G. J.; Roberts, R. A. J. Org. Chem. 1987, 52, 2960−2962.
(14) Ogura, A.; Yamada, K.; Yokoshima, S.; Fukuyama, T. Org. Lett. 2012, 14, 1632−1635.
(15) Peng, F.; Danishefsky, S. J. J. Am. Chem. Soc. 2012, 134, 18860−18867.
(16) Millar, J. G.; Moreira, J. A.; McElfresh, J. S.; Daane, K. M.; Freund, A. S. Org. Lett. 2009, 11, 2683−2685.
(17) For example, see: Cockerill, A. F. in Comprehensive Chemical Kinetics, Addition and Elimination Reactions
of Aliphatic Compounds, Vol. 9; Bamford, C. H., Tipper, C. F. H., Eds.; Elsevier Science: New York, 1973,
Chapter 3.
(18) Mantrand, N.; Renaud, P. Tetrahedron 2008, 64, 11860−11864.
(19) Zhu, M.ꢀK.; Chen, Y.ꢀC.; Loh, T.ꢀP. Chem. Eur. J. 2013, 19, 5250−5254.
(20) Umehara, T.; Inouye, Y.; Kakisawa, H. Bull. Chem. Soc. Jpn. 1981, 54, 3492ꢀ3494.
(21) Hirokawa, Y.; Kitamura, M.; Mizubayashi, M.; Nakatsuka, R. Kobori, Y.; Kato, C.; Kurata, Y.; Maezaki, N.
Eur. J. Org. Chem. 2013, 721−727.
(22) Ryu, I.; Hirai, A.; Suzuki, H.; Sonoda, N.; Murai, S. J. Org. Chem. 1990, 55, 1409−1410.
(23) (a) Schöllkopf, U. Angew. Chem. Int. Ed. 1970, 9, 763−765; (b) Schöllkopf, U.; Fellenberger, K.; Rizk, M.
Justus Liebigs Ann. Chem. 1970, 734, 106−115; (c) Baldwin, J. E.; Patrick, J. E. J. Am. Chem. Soc. 1971, 93,
3556−3558; (d) Rautenstrauch, V. Helv. Chim. Acta 1972, 55, 594−609.
(24) (a) Sayo, N.; Kimura, Y.; Nakai, T. Tetrahedron Lett. 1982, 23, 3931−3934; (b) Nakai, T.; Mikami, K. Org.
React. 1994, 46, p. 114.
(25) Tomooka, K.; Igarashi, T.; Nakai, T. Tetrahedron 1994, 50, 5927−5932.
(26) Didier, P.; Pommier, J.ꢀC. J. Organomet. Chem. 1978, 150, 203−214.
(27) Boche, G.; Bosold, F.; Lohrenz, J. C. W.; Opel, A.; Zulauf, P. Chem. Ber. 1993, 126, 1873−1885.
(28) Diao, T.; Stahl, S. S. J. Am. Chem. Soc. 2011, 133, 14566−14569.
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(29) Matoba, K.; Maeda, T.; Nagase, K.; Yamazaki, T. Chem. Pharm. Bull. 1976, 24, 165−168.
(30) Lemieux, R. M.; Meyers, A. I. J. Am. Chem. Soc. 1998, 120, 5453−5457.
(31) Akers, J. A.; Bryson, T. A. Tetrahedron Lett. 1989, 30, 2187−2190.
(32) Srikishna, A.; Kumar, P. P. Tetrahedron 2000, 56, 8189−8195.
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(33) Clark, J. R.; French, J. M.; Jecs, E.; Diver, S. T. Org. Lett. 2012, 14, 4178−4181.
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