Mild and tunable benzoic acid catalysts for rearrangement reactions of allylic alcohols

Article abstract of DOI:10.1021/jo201540p

An efficient and simple catalytic method for the isomerization of readily prepared allylic alcohols is described. We focus particularly on cyclic examples and the synthesis of unusual enyne and dienols. The benzoic acid catalysts employed are commercially available and very inexpensive and can be tuned for reactivity and substrate sensitivity.

Full text of DOI:10.1021/jo201540p

NOTE
pubs.acs.org/joc
Mild and Tunable Benzoic Acid Catalysts for Rearrangement
Reactions of Allylic Alcohols
J. Adam McCubbin,* Samantha Voth, and Oleg V. Krokhin
Department of Chemistry, University of Winnipeg, 515 Portage Avenue, Winnipeg, MB R3B 2E9, Canada
S Supporting Information
b
ABSTRACT: An efficient and simple catalytic method for the isomerization of
readily prepared allylic alcohols is described. We focus particularly on cyclic
examples and the synthesis of unusual enyne and dienols. The benzoic acid
catalysts employed are commercially available and very inexpensive and can be
tuned for reactivity and substrate sensitivity.
earrangement reactions, whereby a functional group is
transposed from one position to another, constitute impor-
R
tant supplements to bond-forming reactions in the synthesis of
complex molecules.1 In this context, the 1,3-rearrangement of
allylic alcohols is particularly useful because of their high
synthetic utility2 and the common case that one isomer is
typically easier to synthesize than the other.3 Classical methods
to perform this transformation typically involve superstoichio-
metric quantities of strong acids under harsh conditions.4 For
example, a recently reported method requires a full 2 equiv of
MeSO3H to mediate this rearrangement.5 Such conditions often
result in poor yields, particularly with sensitive substrates, due a
myriad of competing reactions, including skeletal rearrange-
ments, eliminations, and formation of oligomeric byproducts.6
Dramatic improvements in terms of scope and selectivity have
been reported recently, either through stoichiometric activation
of the alcohol functionality7 or with the use of transition-metal
oxo complexes.8,9 However, it would be ideal to avoid the waste
generated from stoichiometric activation and the cost and
toxicity associated with transition-metal catalysts.
Figure 1. Metal-free rearrangement catalysts.
competing factors. Under these reaction conditions, 2a was
isolated in near-quantitative yield (Table 1, entry 1). We next
investigated the scope of this reaction on a variety of cyclic allylic
alcohols. Cycloheptanol analogue 1b afforded the product 2b in
similarly high yield as for 2a (entry 2). For most of the cylclic
allylic alcohols tested, salicylic acid (4a) proved to be the optimal
catalyst in terms of reaction time and substrate sensitivity.
However, cyclopentenol 1c proved to be substantially more
sensitive than 1a or 1c, and the molecule decomposed when
treated with catalyst 4a (entry 3). We reasoned that a less acidic
catalyst would be more appropriate for this substrate and were
pleased to observe formation of the desired product (2c) in high
yield upon treatment with benzoic acid (4b, pKa = 4.19) under
otherwise identical conditions (entry 4). Aliphatic substrates
1dÀf showed a moderate increase in yield of products 2dÀf with
increasing bulk of the ring substituent. Electron-rich aromatic ring
substituents also proved suitable (entry 8), whereas electron-poor
Our interest in this reaction began with attempts to rearrange
alcohol 1a to 2a using perfluorinated phenylboronic acid 3
(Figure 1).10 Even after extensive screening of reaction condi-
tions, we achieved only poor yields of 2a along with significant
formation of elimination products.11
Additional screening of acid catalysts and reaction conditions
identified 10 mol % of salicylic acid (4a, pKa = 2.97) in MeCN at
ambient temperature to be most effective in terms of reaction
rate, although with significant formation of dimerized ether
dehydration products. Addition of small amounts of water
improved the yield of desired product, although the time
required for complete conversion increased. A 5:1 mixture of
MeCN/water proved to be the best compromise for these
Received: July 29, 2011
Published: September 13, 2011
r
2011 American Chemical Society
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|

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NOTE
Table 1. Rearrangement of Cyclic Allylic Alcohols
Table 2. Rearrangement of Acyclic Allylic Alcohols
a Isolated yields. b Complete recovery of unreacted starting material.
in excellent yield (entry 10). Bulky aromatic substituents in sub-
strates 1i and 1j had little effect on the reaction, whereas the very
bulky 1-naphthyl-substituted 1k had a moderate effect on product
yield (entry 13). Vinyl substitution appears to have some effect on
substrate reactivity. γ-Substituted 1l reacted cleanly to afford tertiary
alcohol 2l with 4a, whereas no reaction was observed with the same
catalyst and 1m. Similarly to entry 10, the use of 4c resulted in much
improved conversion of 1m to 2m.
Having established the scope of the rearrangement reaction
for cyclic allylic alcohols, we turned our attention to acyclic
alcohols (Table 2). The use of salicylic acid at room temperature
proved ineffective at catalyzing the rearrangement of 5aÀe, with
(at best) only trace amounts of product isolated (entry 3).
However, heating the same mixtures resulted in good to
excellent yields of 6aÀc and 6e (entries 2, 4, 7, and 11).
Alternatively, the more acidic catalyst 4c can be employed at
room temperature for the rearrangement of 5b to 6b (entry 5).
Similarly to 1m, β-substituted substrate 5d (entry 9) was
substantially less reactive than unsubstituted analogues. Rearran-
gement was found to occur upon heating with 4c, which resulted
in an isolated yield of 74% for 6d.
We attribute this limited reactivity to the increased steric
crowding at the alcohol, which may limit access of the catalyst. In
all cases, complete selectivity for the E-isomer was observed, a
significant result given the modest selectivities observed for
similar substrates with alternative catalysts.8,11 Furthermore, no
dimerization products were observed for these less sterically
hindered substrates, even at elevated temperatures.
The efficiency of these catalysts in promoting the rearrange-
ment of allylic alcohols and particularly those with a propensity to
form highly stabilized carbocations, suggested that they might be
well suited to the rearrangement of bis-allylic and allylicÀ
propargylic alcohols. The potential conjugated products are found in
a Isolated yields. b complete decomposition of starting material. c 1:2
mixture of cis/trans isomers.
derivatives reacted sluggishly in the presence of 4a (entry 9) with
significant recovery of starting material. However, increasing the
acidity of the catalyst by using 4c (pKa = 1.53) afforded the product
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NOTE
Table 3. Conjugated Dienes and Enynes
Scheme 1. Reaction with Alcohols
Scheme 2. Mechanistic Probes
observed in the case of 9c.17 When allyl alcohol is used, the
resulting diene 9d is isolated in excellent yield.
Two preliminary experiments shed light on a possible me-
chanism for this transformation. Subjecting homochiral carvone-
derived substrate 1m to either catalyst 4a at reflux or 4c at room
temperature results in an identical 2:1 mixture of trans/cis
diastereomeric products (Scheme 2 (a)). This suggests an ionic
mechanism involving formation of an allylic carbocation fol-
lowed by preferred attack of water from the least hindered face.
Formation of such a carbocation is consistent with our observa-
tion that electron-rich substrates (e.g., 1g) rearrange efficiently
under these conditions, whereas electron-poor derivatives (e.g.,
1h) require more forcing conditions. Furthermore, increasing
the acidity of the catalysts (e.g., from 4a to 4c) results in
increased reactivity for substrates that react via poorly stabilized
carbocations. Such results are also consistent with an ionic
mechanism.
In a second experiment (Scheme 2 (b)), reaction times for
conversion of 1a and 2a to 9a were compared. Compound 1a
reacts rapidly, whereas 2a requires longer reaction times and
results in lower yield of 9a, with starting material recovered. This
suggests a common carbocation intermediate and that the
regiochemistry of the rearrangement is governed by product
stability.
In summary, we have developed a mild, catalytic system for the
rearrangement of allylic alcohols and preparation of allylic ethers.
The acidity (and thus the reactivity) of the catalysts can be tuned
for substrate sensitivity/reactivity; they are very inexpensive and
nontoxic. The products, including synthetically useful conju-
gated dienes and enynes, are produced in high yields and with
excellent selectivity for the E-isomers. Preliminary mechanistic
investigations suggest an ionic mechanism. Further expansion of
the scope of this reaction and mechanistic experiments are
ongoing in our laboratory and will be reported in due course.
a Isolated yields.
natural products12 and are substrates of high synthetic utility in
DielsÀAlder13 and related cycloaddition reactions.14 A scalable
route to such products would therefore be highly desirable.15
Indeed, we observed excellent yields for the conversion of
aryl-, alkyl-, and silyl-substituted cyclic allylicÀpropargylic alcohols
7aÀc to conjugated enynes 8aÀc (Table 3). Acyclic substrate 7d
also performed well under these conditions, affording 8d in good
yield and with complete selectivity with respect to the geometry of
the rearranged alkene. Remarkably, all substrates showed complete
selectivity for alkene rearrangement, despite the propensity for acid
catalysts to promote the related MeyerÀSchuster rearrangement.16
Similarly high selectivities were observed in the bis-allylic
alcohol series. Rearrangement of vinyl-substituted cyclohexenols
7e and 7f occurs exclusively over the endocyclic double bond to
form 8e and 8f, respectively, in high yields. This result is in
contrast to our observation of exclusive exocyclic double bond
selectivity in the FriedelÀCrafts arylation of similar substrates.10
Acyclic bis-allylic substrate 7g rearranged to form 8g as the
exclusive product in good yield and with complete E-selectivity.
The necessity for addition of an external nucleophile
prompted us to examine the use of other oxygen-based nucleo-
philes in this reaction. Simple alcohols, when used in place of
water as an additive, result in the formation of allylic ethers in
good to near-quantitative yields (Scheme 1). A decrease in yield
is observed as the steric hindrance of the alcohol increases (cf.
9aÀc), with significant formation of ether dimerization products
’ EXPERIMENTAL SECTION
Allylic alcohol substrates (1, 5, 7) were prepared according to
previously reported procedures.10
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NOTE
1-sec-Butyl-cyclohex-2-enol (1e): 1H NMR (400 MHz,
CDCl3) δ 5.81À5.75 (m, 1H), 5.53À5.48 (d, J = 10.0 Hz, 1H),
2.02À1.97 (m, 1H), 1.97À1.93 (m, 1H), 1.89À1.79 (m, 1H),
1.74À1.70 (m, 2H), 1.63À1.58 (m, 2H), 1.55À1.45 (m, 2H),
1.36À1.29 (m, 1H), 0.89À0.77 (m, 7H); 13C NMR (100 MHz, CDCl3)
δ 132.8, 132.7, 130.5, 130.1, 72.0, 71.9, 45.2, 45.0, 30.7, 30.3, 25.3, 25.2,
24.6, 22.9, 18.54, 18.52, 13.9, 12.8, 12.7, 12.6; FTIR (neat) υ 3449, 3016,
2832, 1708, 1460, 1380, 1172, 1069, 850, 736 cmÀ1; HRMS (m/z) calcd
for C10H17 (MALDI-TOF, (M À OH)+) 137.1331, found 137.1330.
1-naphthalen-1-yl-cyclohex-2-enol (1k): 1H NMR (400
MHz, CDCl3) δ 8.84À8.81 (d, J = 7.5 Hz, 1H), 7.99À7.95 (d, J = 7.3
Hz, 1H), 7.90À7.86 (m, 2H), 7.61À7.57 (m, 2H), 7.56À7.51 (dd, J =
7.5 Hz, J = 7.8 Hz, 1H), 6.16À6.11 (dt, J = 10.0 Hz, J = 3.5 Hz, 1H),
6.06À6.02 (d, J = 10.0 Hz, 1H), 2.73 (s, br, 1H), 2.61À2.53 (m, 1H),
2.29À2.25 (m, 2H), 2.22À2.15 (m, 1H), 2.01À1.91 (m, 1H),
1.72À1.63 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 142.3, 135.0,
134.0, 130.7, 129.8, 129.2, 128.6, 126.8, 125.3, 125.2, 125.0, 124.9, 73.7,
37.3, 25.1, 19.6; FTIR (neat) υ 3419, 2924, 2855, 1458, 1377, 1167, 966,
904, 739 cmÀ1; HRMS (m/z) calcd for C16H15 (MALDI-TOF, (M À
OH)+) 207.1174, found 207.1179.
afford 2c (138 mg, 86%): 1H NMR (400 MHz, CDCl3) δ 7.42À7.50 (d,
J = 7.0 Hz, 2H), 7.21À7.33 (m, 3H), 6.20À6.23 (s, 1H), 4.97À5.02 (m,
1H), 2.81À2.84 (m, 1H), 2.60À2.63 (m, 1H), 2.40À2.42 (m, 1H),
1.81À1.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 146.1, 135.7,
128.5, 127.9, 127.3, 126.0, 77.0, 33.8, 31.4; FTIR (neat) ν 3406, 3079,
3055, 2935, 2246, 1947, 1877, 1802, 1737, 1598, 1493, 1069, 757 cmÀ1
;
HRMS (m/z) calcd for C11H11 (MALDI-TOF, (M À OH)+) 143.0861,
found 143.0868.
3-sec-Butylcyclohex-2-enol (2e). Prepared according to general
procedure A with 1e (154 mg) and 4a (14 mg) at room temperature to
1
afford 2e (134 mg, 87%): H NMR (400 MHz, CDCl3) δ 5.46À5.49
(m, 1H), 4.16À4.21 (m, 1H), 2.10À2.13 (br, 1H), 1.92À2.00 (m, 2H),
1.70À1.85 (m, 2H), 1.52À1.60 (m, 2H), 1.34À1.42 (m, 1H),
1.26À1.32 (m, 1H), 0.96À1.00 (d, J = 7.0 Hz, 3H), 0.85À0.90 (m,
1H), 0.79À0.85 (m, 3H); 13C NMR (100 MHz, CDCl3) δ 146.0, 123.4,
65.8, 42.5, 32.2, 27.6, 25.2, 19.2, 18.9, 11.8; FTIR (neat) ν 3360, 2660,
1709, 1662, 1456, 1059, 1023, 909, 759 cmÀ1; HRMS (m/z) calcd for
C10H17 (MALDI-TOF, (M À OH)+) 137.1331, found 137.1326.
3-tert-Butylcyclohex-2-enol (2f). Prepared according to general
procedure A with 1f (154 mg) and 4a (14 mg) at room temperature to
afford 2f (140 mg, 91%): 1H NMR (400 MHz, CDCl3) δ 5.53À5.55 (m,
1H), 4.18À4.23 (m, 1H), 1.90À2.10 (m, 2H), 1.76À1.84 (m, 1H),
1.66À1.59 (m, 1H), 1.52À1.58 (m, 2H), 1.48À1.51 (m, 1H),
1.01À1.04 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 150.1, 120.3,
66.5, 35.3, 31.9, 28.8, 24.6, 19.9, 14.4; FTIR (neat) ν 3405, 3050, 2960,
2866, 1712, 1395, 1367, 1280, 1073, 1027, 999 cmÀ1; HRMS (m/z)
calcd for C10H17 (MALDI-TOF, (M À OH)+) 137.1331, found
137.1330.
1-Oct-1-ynyl-cyclohex-2-enol (7b): 1H NMR (400 MHz,
CDCl3) δ 5.60À5.58 (m, 2H), 2.07À2.02 (t, J = 7.3 Hz, 2H),
1.88À1.80 (m, 3H), 1.77À1.71 (m, 1H), 1.65À1.56 (m, 2H),
1.39À1.31 (m, 2H), 1.27À1.18 (m, 2H), 1.19À1.11 (m, 4H),
0.77À0.72 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
131.4, 128.2, 84.1, 83.8, 65.0, 38.0, 31.2, 28.5, 28.4, 24.6, 22.4, 19.2,
18.6, 13.9; FTIR (neat) ν 3367. 2932, 2859, 2232, 1456, 1322, 1182,
1054, 959, 737 cmÀ1; HRMS (m/z) calcd for C14H21 (MALDI-TOF,
(M À OH)+) 189.1644, found 189.1638.
3-(4-Methoxyphenyl)cyclohex-2-enol (2g). Prepared accord-
ing to general procedure A with 1g (204 mg) and 4a (14 mg) at room
temperature to afford 2g (175 mg, 86%): 1H NMR (400 MHz, CDCl3)
δ 7.31À7.35 (d, J = 8.8 Hz, 2H), 6.83À6.86 (d, J = 8.8 Hz, 2H),
6.05À6.07 (m, 1H), 4.34À4.38 (m, 1H), 3.77 (s, 3H), 2.25À2.45 (m,
3H), 1.86À1.92 (m, 2H), 1.64À1.70 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 158.1, 138.7, 133.7, 126.1, 124.9, 113.4, 65.9, 54.9, 31.5, 27.2,
19.2; FTIR (Nujol) ν 3336, 3034, 2723, 2052, 1902, 1640, 1607, 1031,
966 cmÀ1; HRMS (m/z) calcd for C13H15O (MALDI-TOF, (M À
OH)+) 187.1123, found 187.1143.
1
3-Methyl-1-phenyl-hexa-1,4-dien-3-ol (7g): H NMR (400
MHz, CDCl3) δ 7.42À7.38 (m, 2H), 7.34À7.29 (m, 2H), 7.25À7.21
(m, 1H), 6.67À6.59 (m, 1H), 6.43À6.38 (d, J = 16.1 Hz, 0.5 H),
6.35À6.30 (d, J = 16.1 Hz, 0.5H), 5.73À5.57 (m, 2H), 2.19 (s, br, 1H),
1.83À1.80 (d, J = 5.5 Hz, 1.5H), 1.75À1.73 (d, J = 5.0 Hz, 1.5H), 1.54 (s,
1.5H), 1.48 (s, 1.5H); 13C NMR (100 MHz, CDCl3) δ 137.1, 137.0,
136.9, 135.89, 135.87, 135.8, 128.6, 128.5, 127.41, 127.39, 127.1, 126.81,
126.77, 126.5, 124.0, 73.4, 72.9, 30.0, 28.4, 17.8, 14.4; FTIR (neat) ν
3419, 3026, 2972, 2928, 1710, 1494, 1448, 1367, 969, 749, 694 cmÀ1
;
HRMS (m/z) calcd for C13H15 (MALDI-TOF, (M À OH)+) 171.1174,
3-(4-Trifluoromethylphenyl)cyclohex-2-enol (2h). Prepared
according to general procedure A with 1h (242 mg) and 4c (23 mg) at
found 171.1181.
1
General Procedure A for the rearrangement of allylic Alcohols. To a
10 mL round-bottom flask containing the substrate (1, 5, or 7, 1.0
mmol) in CH3CN (5 mL) and H2O (1 mL) was added catalyst 4a, b, or
c (0.1 mmol). The flask was either loosley capped with a septum and the
resulting mixture allowed to stir at room temperature for 16 h or fitted
with a condensor and heated to reflux for 16 h and cooled to room
temperature. A saturated solution of NaHCO3 (20 mL) was added and
the mixture extracted with Et2O (2 Â 25 mL). The combined organic
extracts were dried over MgSO4 and concentrated. Purification (if
necessary) of the residue by flash chromatography (EtOAc/hexanes)
afforded the products 2, 6, and 8.
room temperature to afford 2h (230 mg, 95%): H NMR (400 MHz,
CDCl3) δ 7.51À7.56 (d, J = 8.0 Hz, 2H), 7.45À7.49 (d, J = 8.2 Hz, 2H),
6.17À6.21 (s, 1H), 4.36À4.41 (s, 1H), 2.75À2.83 (s, 1H), 2.26À2.46
(m, 2H), 1.87À1.96 (m, 2H), 1.87À1.96 (m, 2H), 1.55À1.80 (m, 2H);
13C NMR (100 MHz, CDCl3) δ 143.3, 136.8, 127.4, 124.0, 123.5, 64.5,
29.8, 25.7, 17.8; FTIR (neat) ν 3350, 3025, 2936, 2865, 1921, 1616,
1410, 1071, 1016, 738 cmÀ1; HRMS (m/z) calcd for C13H12F3
(MALDI-TOF, (M À OH)+) 225.0891, found 225.0907.
3-o-Tolylcyclohex-2-enol (2i). Prepared according to general
procedure A with 1i (188 mg) and 4a (14 mg) at room temperature to
afford 2i (175 mg, 93%): 1H NMR (400 MHz, CDCl3) δ 7.02À7.15 (m,
5H), 4.31À4.35 (m, 1H), 2.10À2.34 (m, 6H), 1.82À1.95 (m, 2H),
1.66À1.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 143.0, 142.3,
134.6, 129.9, 128.2, 127.9, 126.7, 124.5, 65.7, 31.5, 30.2, 19.4, 19.5; FTIR
(neat) ν 3342, 3059, 3016, 2929, 2860, 1945, 1911, 1801, 1702, 1660,
1601, 1485, 1052, 756 cmÀ1; HRMS (m/z) calcd for C13H16 (MALDI-
TOF, (M À OH)+) 171.1174, found 171.1189.
3-Phenylcyclohept-2-enol (2b). Prepared according to general
procedure A with 1b (188 mg) and 4a (14 mg) at room temperature to
afford 2b (177 mg, 94%): 1H NMR (400 MHz, CDCl3) δ 7.22À7.32 (m,
4H), 7.15À7.21 (m, 1H), 5.96À6.01 (m, 1H), 4.52À4.57 (m, 1H),
2.72À2.82 (s, br, 1H), 2.58À2.62 (dd, J = 15.1 Hz, J = 6.5 Hz, 1H),
2.38À2.49 (m, 1H), 1.92À2.10 (m, 1H), 1.82À1.88 (m, 1H), 1.72À1.81
(m, 1H), 1.64À1.72 (m, 2H), 1.35À1.45 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ143.9, 141.5, 136.0, 128.1, 126.0, 125.6, 71.8, 36.3, 32.5, 28.0, 26.1;
FTIR (neat) ν 3387, 3079, 3056, 3027, 2927, 2851, 1948, 1879, 1804, 1687,
1645, 1598, 1493, 1080, 761 cmÀ1; HRMS (m/z) calcd for C13H15
(MALDI-TOF, (M À OH)+) 171.1174, found 171.1166.
3-Naphthalen-2-ylcyclohex-2-enol (2j). Prepared according to
general procedure A with 1j (224 mg) and 4a (14 mg) at room
temperature to afford 2j (170 mg, 76%): 1H NMR (400 MHz, CDCl3)
δ 7.79À7.76 (dd, J = 6.3 Hz, J = 3.5 Hz, 1H), 7.75À7.71 (m, 4H),
7.70À7.66 (d, J = 8.5 Hz, 1H), 6.22À6.24 (m, 1H), 3.35À4.40 (m, 1H),
2.30À2.50 (m, 3H), 1.80À1.98 (m, 3H), 1.60À1.75 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 139.3, 138.3, 133.3, 132.6, 127.9, 127.6, 127.3,
3-Phenylcyclopent-2-enol (2c). Prepared according to general
procedure A with 1c (160 mg) and 4b (12 mg) at room temperature to
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NOTE
125.9, 125.6, 123.8, 123.6, 66.1, 31.5, 27.2, 19.4; FTIR (Nujol) ν 3310,
3052, 1627, 1594, 1376, 1054, 976, 782, 744 cmÀ1; HRMS (m/z) calcd
for C16H15 (MALDI-TOF, (M À OH)+) 207.1174, found 207.1176.
3-Naphthalen-1-ylcyclohex-2-enol (2k). Prepared according
to general procedure A with 1k (224 mg) and 4a (14 mg) at room
temperature to afford 2k (199 mg, 89%): 1H NMR (400 MHz, CDCl3)
δ 7.93À7.96 (dd, J = 4.5 Hz, J = 3.3 Hz, 2H), 7.75À7.80 (dd, J = 6.0 Hz, J
= 3.8 Hz, 2H), 7.67À7.71 (d, J = 8.3 Hz, 1H), 7.33À7.43 (m, 4H),
7.19À7.23 (m, 1H), 2.17À2.41 (m, 2H), 1.85À2.01 (m, 2H),
1.65À1.80 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 141.4, 141.1,
133.6, 130.9, 129.7, 128.2, 127.1, 125.7, 125.5, 125.4, 125.2, 124.6, 65.7,
31.6, 31.1, 19.6; FTIR (neat) ν 3359, 3055, 2929, 2859, 1929, 1812,
1662, 1449, 1057, 735 cmÀ1; HRMS (m/z) calcd for C16H15 (MALDI-
TOF, (M À OH)+) 207.1174, found 207.1173.
temperature to afford 8g (141 mg, 75%): 1H NMR (400 MHz, CDCl3)
δ 7.41À7.45 (d, J = 7.3 Hz, 2H), 7.31À7.36 (dd, J = 7.3 Hz, J = 15.1 Hz,
3H), 7.22À7.26 (d, J = 7.3 Hz, 1H), 6.76À6.82 (d, J = 16.3 Hz, 1H),
6.54À6.59 (d, J = 16.1 Hz, 1H), 5.63À5.66 (d, J = 16.1 Hz, 1H),
5.63À5.66 (d, J = 8.5 Hz, 1H), 4.73À4.80 (m, 1H), 1.93À1.94 (s, 3H),
1.31À1.33 (s, 3H) ; 13C NMR (100 MHz, CDCl3) δ 137.4, 136.5, 134.5,
133.0, 128.6, 128.6, 128.0, 127.3, 126.4, 64.7, 23.5, 12.7; FTIR (neat) ν
3417, 3060, 3027, 2972, 2928, 2247, 1950, 1880, 1805, 1708, 1599,
1493 cmÀ1; HRMS (m/z) calcd for C13H15 (MALDI-TOF, (M À
OH)+) 171.1174, found 171.1165.
General Procedure B for the Preparation of Allylic Ethers. To a vial
containing 1a (174 mg, 1.0 mmol) in CH3CN (5 mL) and the alcohol
(1 mL) was added catalyst 4a (0.1 mmol, 14 mg). The vial was capped
and the mixture allowed to stir at room temperature for 16 h. A saturated
solution of NaHCO3 (20 mL) was added and the mixture extracted with
Et2O (2 Â 25 mL). The combined organic extracts were dried over
MgSO4 and concentrated. Purification (if necessary) of the residue by
flash chromatography (EtOAc/hexanes) afforded the products 5.
1-(3-Methoxycyclohex-1-enyl)benzene (9a). Prepared ac-
cording to general procedure B with methanol to afford 9a (184 mg,
98%): 1H NMR (400 MHz, CDCl3) δ 7.39À7.41 (d, J = 7.0 Hz, 2H),
7.20À7.31 (m, 2H), 6.15À6.17 (m, 1H), 3.82À3.89 (m, 1H), 3.40 (s,
1H), 2.35À2.45 (m, 1H), 1.87À1.91 (m, 4H), 1.66À1.72 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 141.2, 140.0, 127.9, 126.9, 125.0, 124.0,
74.6, 55.5, 27.4, 19.3; FTIR (neat) ν 3371, 2935, 1668, 1446, 1348. 1258,
1190, 1095, 945, 758, 694 cmÀ1; HRMS (m/z) calcd for C12H13
(MALDI-TOF, (M À OMe)+) 157.1017, found 157.1006.
1-Methyl-3-phenylcyclohex-2-enol (2l). Prepared according
to general procedure A with 1l (188 mg) and 4a (14 mg) at room
temperature to afford 2l (158 mg, 84%): 1H NMR (400 MHz, CDCl3) δ
7.40À7.44 (m, 2H), 7.26À7.29 (m, 3H), 6.04À6.06 (s, 1H), 2.00À2.39
(m, 4H), 1.59À1.80 (m, 5H), 1.31À1.32 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 139.5, 131.2, 128.4, 123.1, 122.5, 68.1, 36.8, 29.4, 28.9, 19.5;
FTIR (neat) ν 3388, 3080, 3055, 2964, 2866, 2204, 1950, 1880, 1714,
1626, 1488, 1070, 1017, 755 cmÀ1; HRMS (m/z) calcd for C13H15
(MALDI-TOF, (M À OH)+) 171.1174, found 171.1166.
3-Phenylethynylcyclohex-2-enol (8a). Prepared according to
general procedure A with 7a (198 mg) and 4a (14 mg) at room
temperature to afford 8a (190 mg, 96%): 1H NMR (400 MHz, CDCl3)
δ 7.37À7.42 (dd, J = 7.3 Hz J = 3.8 Hz, 2H), 7.23À7.27 (m, 3H),
6.15À6.18 (m, 1H), 4.23À4.28 (m, 1H), 2.60À2.70 (s, br, 1H),
2.10À2.28 (m, 2H), 1.72À1.90 (m, 2H), 1.52À1.64 (m, 2H); 13C
NMR (100 MHz, CDCl3) δ 135.9, 131.3, 127.9, 123.6, 123.4, 123.1,
89.8, 88.5, 65.3, 30.8, 29.2, 18.9; FTIR (neat) ν 3358, 3079, 3055, 2934,
1-(3-Isopropoxycyclohex-1-enyl)benzene (9b). Prepared ac-
cording to general procedure B with 2-propanol to afford 9b (201 mg,
93%): 1H NMR (400 MHz, CDCl3) δ 7.39À7.43 (m, 2H), 7.28À7.33
(m, 2H), 7.23À7.25 (m, 1H), 6.08À6.10 (m, 1H), 4.08À4.12 (s, 1H),
2.30À2.50 (m, 3H), 1.94À1.96 (s, 3H), 1.66À1.70 (m, 2H), 1.18À1.22
(d, J = 6.0 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 141.3, 139.3, 127.8,
126.8, 125.4, 125.0, 70.7, 68.8, 28.7, 27.2, 22.8, 22.4, 19.5; FTIR (neat) ν
3453, 3082, 3057, 3031, 2968, 2934, 2863, 1944, 1884, 1806, 1711, 1676,
1643, 1598, 1577 cmÀ1; HRMS (m/z) calcd for C12H13 (MALDI-TOF,
(M À OiPr)+) 157.1017, found 157.1000.
2204, 1950, 1880, 1804, 1664, 1627, 1596, 1488, 1069, 755 cmÀ1
;
HRMS (m/z) calcd for C14H13O (MALDI-TOF, (M À H)+) 197.0967,
found 197.0958.
3-Oct-1-ynylcyclohex-2-enol (8b). Prepared according to gen-
eral procedure A with 7b (206 mg) and 4a (14 mg) at room temperature
to afford 8b (200 mg, 97%): 1H NMR (400 MHz, CDCl3) δ 5.96À5.90
(m, 1H), 4.18À4.22 (m, 1H), 2.53À2.58 (s, br, 1H), 2.56À2.30 (t, J =
7.0 Hz, J = 14.3 Hz, 2H), 2.00À2.16 (m, 2H), 1.70À1.86 (m, 2H),
1.46À1.60 (m, 4H), 1.24À1.42 (m, 6H), 0.86À0.92 (t, J = 6.5 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 134.0, 123.9, 89.4, 80.9, 64.9, 36.8, 31.5,
30.9, 29.4, 28.3, 22.2, 18.8, 13.6; FTIR (neat) ν 3350, 3030, 2953, 2221,
1666, 1630, 1432, 1063, 969, 725 cmÀ1; HRMS (m/z) calcd for C14H21
(MALDI-TOF, (M À OH)+) 189.1644, found 189.1642.
1-(3-tert-Butoxycyclohex-1-enyl)benzene (9c). Prepared ac-
cording to general procedure B with tert-butyl alcohol to afford 9c (166
mg, 72%): 1H NMR (400 MHz, CDCl3) δ 7.39À7.44 (m, 2H),
7.28À7.33 (m, 2H), 7.21À7.27 (m, 1H), 5.98À6.00 (m, 1H),
4.18À4.22 (s, 1H), 2.29À2.47 (m, 2H), 1.87À1.88 (s, 2H),
1.64À1.76 (m, 3H), 1.27À1.29 (m, 9H); 13C NMR (100 MHz, CDCl3)
δ 141.3, 138.4, 127.6, 127.4, 126.5, 124.8, 73.1, 65.7, 30.9, 27.9, 26.7,
20.1; FTIR (neat) ν 3504, 3027, 2958, 2870, 1390, 1366, 1270, 1221,
1164, 1123, 1086, 1044, 1015, 958 cmÀ1; HRMS (m/z) calcd for
C12H13 (MALDI-TOF, (M À OtBu)+) 157.1017, found 157.1019.
1-(3-Allyloxycyclohex-1-enyl)benzene (9d). Prepared ac-
cording to general procedure B with allyl alcohol to afford 9d (203
mg, 95%): 1H NMR (400 MHz, CDCl3) δ 7.43À7.46 (d, J = 7.2 Hz,
2H), 7.31À7.36 (t, J = 7.2 Hz, J = 14.8 Hz, 2H), 7.24À7.26 (t, J = 7.2 Hz,
J = 14.5 Hz, 1H), 6.19À6.21 (s, 1H), 5.93À6.03 (m, 1H), 5.32À5.39
(dd, J =15.3 Hz, J = 17.1 Hz, 1H), 5.20À5.24 (dd, J = 8.7 Hz, J = 10.5 Hz,
1H), 4.08À4.18 (m, 3H), 2.45À2.54 (m, 1H), 2.34À2.43 (m, 1H),
1.89À2.01 (m, 2H), 1.68À1.80 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 140.9, 139.6, 134.8, 127.6, 126.6, 124.7, 124.1, 115.9, 72.4, 68.6, 27.4,
27.0, 19.1; FTIR (neat) ν 33131, 3081, 3057, 3031, 2936, 2861, 2663,
1947, 1873, 1804, 1712 cmÀ1; HRMS (m/z) calcd for C12H13 (MALDI-
TOF, (M À O-allyl)+) 157.1017, found 157.1016.
3-Methyl-1,5-diphenylpent-2-en-4-yn-1-ol (8d). Prepared
according to general procedure A with 7d (248 mg) and 4a (14 mg)
at room temperature to afford 8d (181 mg, 73%): 1H NMR (400 MHz,
CDCl3) δ 7.47À7.52 (m, 4H), 7.34À7.40 (m, 5H), 7.26À7.32 (m, 1H),
5.91À5.95 (d, J = 9.0, 1H), 5.85À5.88 (d, J = 9.0 Hz, 1H), 2.22À2.25 (s,
1H), 1.98À2.01 (s, 3H); 13C NMR (100 MHz, CDCl3) 137.3, 128.4,
127.6, 125.8, 124.1, 110.5, 67.9, 14.8; FTIR (neat) ν 3353, 3060, 3027,
2930, 2316, 1600, 1494, 1449, 1020, 967, 743 cmÀ1; HRMS (m/z) calcd
for C18H15O (MALDI-TOF, (M À H)+) 247.1123, found 247.1107.
3-Isopropenylcyclohex-2-enol (8f). Prepared according to gen-
eral procedure A with 7f (138 mg) and 4a (14 mg) at room temperature
to afford 8f (123 mg, 89%): 1H NMR (400 MHz, CDCl3) δ 5.85À5.87 (s,
1H), 5.04À5.06 (s, 1H), 4.92À4.94 (s, 1H), 4.28À4.36 (s, br, 1H),
2.39À2.42 (m, 1H), 2.18À2.22 (m, 2H), 1.89À1.91 (m, 4H), 1.50À1.65
(m, 3H); 13C NMR (100 MHz, CDCl3) δ 142.8, 138.9, 126.9, 111.8, 66.3,
31.5, 25.1, 20.0, 19.2; FTIR (neat) ν 3416, 3022, 2939, 2834, 1708, 1438,
1168, 1056, 967, 901, 740 cmÀ1; HRMS (m/z) calcd for C9H13 (MALDI-
TOF, (M À OH)+) 121.1018, found 121.1022.
’ ASSOCIATED CONTENT
S
Supporting Information. General experimental meth-
4-Methyl-6-phenylhexa-3,5-dien-2-ol (8g). Prepared accord-
ing to general procedure A with 7g (188 mg) and 4a (14 mg) at room
b
ods and H and 13C NMR spectra for all new compounds and
1
8541
dx.doi.org/10.1021/jo201540p |J. Org. Chem. 2011, 76, 8537–8542

The Journal of Organic Chemistry
NOTE
known compounds prepared by new methods. This material is
available free of charge via the Internet at http://pubs.acs.org/.
(12) For reviews, see: (a) Chinchilla, R.; Najera, C. Chem. Rev. 2007,
107, 874. (b) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem., Int.
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(15) An extensive search of the literature yielded only two rearran-
gement methods for the synthesis of conjugated enynes. Both require
stoichiometric preactivation of the allylic alcohol substrate by esterifica-
tion: (a) Shull, B. K.; Koreeda, M. J. Am. Chem. Soc. 1996, 118, 11690.
(b) Serra-Muns, A.; Guerinot, A.; Reymond, S.; Cossy, J. Chem.
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(16) No evidence of dienone products was observed in NMR spectra
of the crude product mixtures. For reviews of the MeyerÀSchuster
rearrangement, see: (a) Swaminathan, S.; Narayanan, K. V. Chem. Rev.
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(17) No alcohol product was observed. When 9c was subjected to
the rearrangement conditions (in, e.g., Table 1), no reaction was
observed.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: a.mccubbin@uwinnipeg.ca.
’ ACKNOWLEDGMENT
We thank the University of Winnipeg for providing financial
support of this work in the form of a Start-up Grant (J.A.M.) and
the Natural Sciences and Engineering Research Council of
Canada (O.V.K.).
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