Alkyl-group selection in an acidic-surfactant-promoted reaction of homoallyl alcohols and aldehydes in water

Article abstract of DOI:10.1002/hlca.200800434

The hydrophobic effect in the reaction of a homoallyl alcohol with an aldehyde (Yadav's reaction system) under aqueous conditions in the presence of an acidic surfactant was studied indicating the presence of the alkyl-substituent effect, although not a dramatic one. The DBSA-promoted reaction proceeds relatively faster when both the homoallyl alcohol and the aldehyde carry a cycloalkyl group (DBSA=4-dodecylbenzenesulfonic acid). In contrast, the reaction of the substrates having an unbranched alkyl group is relatively more favorable in SDS/HCl than in DBSA (SDS=sodium dodecyl sulfate).

Full text of DOI:10.1002/hlca.200800434

Helvetica Chimica Acta – Vol. 92 (2009)
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Alkyl-Group Selection in an Acidic-Surfactant-Promoted Reaction of
Homoallyl Alcohols and Aldehydes in Water
by Takanori Hatakeyamaa), Yuki Chisakaa), and Chiaki Kuroda*a)b)
a) Department of Chemistry, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan
b) Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro, Toshima-ku,
Tokyo 171-8501, Japan (phone/fax: þ 81-339852396; e-mail: chkkuroda@grp.rikkyo.ne.jp)
The hydrophobic effect in the reaction of a homoallyl alcohol with an aldehyde (Yadavꢀs reaction
system) under aqueous conditions in the presence of an acidic surfactant was studied indicating the
presence of the alkyl-substituent effect, although not a dramatic one. The DBSA-promoted reaction
proceeds relatively faster when both the homoallyl alcohol and the aldehyde carry a cycloalkyl group
(DBSA ¼ 4-dodecylbenzenesulfonic acid). In contrast, the reaction of the substrates having an
unbranched alkyl group is relatively more favorable in SDS/HCl than in DBSA (SDS ¼ sodium dodecyl
sulfate).
Introduction. – Organic reactions in H2O have been extensively developed recently
[1]. In the reactions of organic substrates in H2O, hydrophobic interaction is an
important factor [2], by which various organic reactions are thought to be controlled.
Thus, it is essential to know the extent of the hydrophobic interaction in an aqueous
organic reaction. For this purpose, as a model study, we planned to evaluate the
hydrophobic effect in Yadavꢀs reaction system [3 – 6], namely in the reaction of a
homoallyl alcohol with an aldehyde to afford a tetrahydro-2H-pyran-4-ol compound
(Scheme 1) via a Prins-type cyclization [7]. In the reaction, the hydrophobic interaction
between R1 and R2 is expected to be present in the initial hemiacetal formation. The
reaction is known to proceed smoothly in dichloromethane [3], in 1,2-dichloroethane
[4], or in an ionic organic solvent [5] giving the tetrahydro-2H-pyran-4-ol derivatives. A
phosphomolybdic acid promoted reaction in H2O has been reported recently [6].
Scheme 1
In the aqueous organic reactions, surfactants are often used to provide the reaction
media by dissolving H2O-insoluble organic materials. Among the various surfactants,
DBSA (4-dodecylbenzenesulfonic acid) is not only a surfactant but also an acid.
Therefore, the compound is useful in the acid-promoted reactions in H2O, such as
ꢁ 2009 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Helvetica Chimica Acta – Vol. 92 (2009)
esterification [8], substitution [9], and cyclization [10] reactions. Since Yadavꢀs reaction
is also promoted under acidic conditions, we planned to use DBSA in the present study.
Here, we report that the yield of the products depend both on the alkyl group of the
reactants and on the surfactant.
Results and Discussion. – In the present study, homoallyl alcohols 1a – 1e and
aldehydes 2a – 2j were used as the substrates, among which 1b – 1e were prepared from
the corresponding aldehydes 2b – 2e and allylmagnesium chloride (3) as shown in
Scheme 2.
Scheme 2
Initially, the Prins-type reaction of 1a – 1c with aldehydes 2a – 2c was examined. The
results are shown in Scheme 3 and Table 1. The reaction of 1a with benzaldehyde (2a)
afforded only 4% of 4aa after 3 days at room temperature, together with 87% of
unreacted 1a (Entry 1). Similarly, products were obtained in only low yield from either
1a (Entries 2 and 3) or 2a (Entries 4 and 7). The reaction proceeded with relatively
better yields when both the homoallyl alcohol and the aldehyde have an aliphatic or
alicyclic R (or R’) group (Entries 5, 6, 8, and 9), among which the reaction of 1b with
cyclohexanecarboxaldehyde (2b) was the fastest, giving the product 4bb in a good yield
after a shorter reaction time (Entry 5). The data indicate that the three substituents can
be ranked in the order cyclohexyl > Me(CH2)6 > Ph with respect to their product yields.
For example, the order of the yields was 4bb > 4bc > 4ab for both the reaction of 1b
(Entries 4 – 6) and that of 2b (Entries 2, 5, and 8). The reaction was found to proceed
slowly with a catalytic amount of DBSA (Entry 10).
Scheme 3
a) See text and Table 1 for the conditions. See Table 1 for the structure of each compound 4.

Helvetica Chimica Acta – Vol. 92 (2009)
1335
Table 1. DBSA-Promoted Reactions of 1a – 1c with 2a – 2c in H2Oa)
Entry
Substrates
Rb)
R’b)
Time [d]
Products (yield [%])c)
1
2
3
4
5
6
7
8
9
1a þ 2a
1a þ 2b
1a þ 2c
1b þ 2a
1b þ 2b
1b þ 2c
1c þ 2a
1c þ 2b
1c þ 2c
1b þ 2b
Ph
Ph
Ph
Chx
Chx
Chx
Me(CH2)6
Me(CH2)6
Me(CH2)6
Chx
Ph
Chx
Me(CH2)6
Ph
Chx
Me(CH2)6
Ph
Chx
Me(CH2)6
Chx
3
3
3
3
1
3
3
2
3
1
4aa (4)
4ab (9), 4bb (17)
4ac (5), 4cc (9)
4ab (43), 4bb (5)
4bb (81)
4bc (50), 4cc (7)d)
4ac (23), 4cc (4)
4bc (55), 4bb (9)d)
4cc (61)
10e)
4bb (20)
a) Reactions were carried out at r.t. with 100 mol-% of DBSA, except for Entry 10. Molar ratio 1/2 1 : 1.5.
b) Chx ¼ cyclohexyl. c) Yield after isolation. d) The two products were not separated; the yields were
determined based on the H-NMR data of the mixture. e) 10 mol-% of DBSA was used.
1
From the reactions of 1a þ 2b (Entry 2) and 1b þ 2a (Entry 4), 4bb was obtained as
a by-product. Similarly, 4cc was obtained from the reaction of both 1a þ 2c (Entry 3)
and 1c þ 2a (Entry 7). This can be explained as follows. The reaction of 1a and 2b
giving 4ab proceeds through intermediate cations A and B, the latter of which is the
same intermediate as generated from the reaction of 1b and 2a via C (Scheme 4). By
the equilibration of A, B, and C, 1b was generated in situ from the reaction of 1a þ 2b,
and similarly, 2b was generated from the reaction of 1b þ 2a. Since the reaction of 1b
and 2b is faster, as described above, the resultant formation of 4bb as the by-product
was observed.
Scheme 4. Expected Reaction Mechanism of the Formation of 4ab.
Since allylsilanes are the H2O-stable carbanion equivalents, the reaction of
aldehydes 2a – 2c and allyltrimethylsilane (5) was also carried out in H2O in the
presence of DBSA, expecting that 4 would be obtained together with 1 (Scheme 5).
When benzaldehyde (2a) was treated with 5, the reaction occurred slowly. After 3
weeks at room temperature, the expected product 1a was isolated in only 16% yield,
along with the 2 :1 product 4aa (3%). From cyclohexanecarboxaldehyde (2b) and

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Helvetica Chimica Acta – Vol. 92 (2009)
octanal (2c), the 1:1 reaction products 1b and 1c were not obtained, but only the 2 :1
products 4bb and 4cc were isolated in 59 and 39% yield, respectively. These results
indicate that the reaction of 1b or 1c with the corresponding aldehyde 2a or 2b was
faster than that of 5.
Scheme 5
a) See text for the conditions.
The reaction was further studied with various substrates, and the results are
summarized in Table 2. When 1b was reacted with 2d or 2e, the corresponding products,
4bd and 4be, were obtained as before (Entries 1 and 2). In contrast, the reactions with
2f – 2j were slow and afforded 4bf – 4bj in low yields, accompanying 4bb as the by-
product (Entries 3 – 7). These results, as well as the results listed in Table 1, suggest that
conjugated aldehydes have low reactivity. No distinct difference was observed between
the substituents Me(CH2)6 and Me(CH2)10 (Entries 8, 11, and 12), and not between the
cyclohexyl and cyclopentyl groups either (Entries 2, 13, and 14).
Table 2. DBSA-Promoted Yadavꢀs Reaction of Various Substratesa)
Entry
Substrates
Rb)
R’b)
Time [d]
Products (yield [%])c)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1b þ 2d
1b þ 2e
1b þ 2f
1b þ 2g
1b þ 2h
1b þ 2i
1b þ 2j
1c þ 2d
1c þ 2e
1d þ 2b
1d þ 2c
1d þ 2d
1e þ 2b
1e þ 2e
Chx
Chx
Chx
Chx
Chx
Chx
Chx
Me(CH2)6
Me(CH2)6
Me(CH2)10
Me(CH2)10
Me(CH2)10
Cpe
Me(CH2)10
Cpe
3
1
3
3
3
3
3
3
2
3
3
3
1
1
4bd (69)
4be (69)d)
Me(CH2)3CH(Et)
cyclohex-1-en-1-yl
(E)-PrCH¼CH
Me2C¼CH
PhCH2
Me(CH2)10
Cpe
Chx
4bf (36), 4bb (15)e)
4bg (12), 4bb (2)e)
4bh (14), 4bb (3)e)
4bi (25), 4bb (3)e)
4bj (42), 4bb (16)
4cd (54)
4ce (65), 4ee (11)e)
4bd (49), 4bb (9)e)
4cd (60)
Me(CH2)6
Me(CH2)10
Chx
4dd (55)
4be (78)d)
Cpe
Cpe
4ee (80)
a) Reactions were carried out at r.t. with 100 mol-% of DBSA. Molar ratio 1/2 1 : 1.5. b) Chx ¼ cyclo-
c
hexyl, Cpe ¼ cyclopentyl. ) Isolated yield. d) 4bb and 4ee were detected by GC, but their amounts were
not determined. e) The two products were not separated; the yields were determined based on the
1H-NMR data of the mixture.
To evaluate the effect of the aromatic ring in DBSA, the reactions were carried out
in the presence of SDS (sodium dodecyl sulfate) and HCl with homoallyl alcohols and

Helvetica Chimica Acta – Vol. 92 (2009)
1337
aldehydes having the same alkyl substituent (R ¼ R’; Table 3). An interesting result
was obtained, namely, the reaction was obviously faster in SDS/HCl than in DBSA (cf.
Tables 1 and 2) when the alkyl group was Me(CH2)6 and Me(CH2)10 (Entries 3 – 5). In
contrast, no difference in surfactant was observed for the cycloalkyl substituents
(Entries 1, 2, and 6).
Table 3. Reactions of 1b – 1e with 2b – 2e in SDS/HCla)
Entry
Substrates
R ¼ R’b)
HCl [equiv.]
Time [d]
Products (yield [%])c)
1
2
3
4
5
6
1b þ 2b
1b þ 2b
1c þ 2c
1c þ 2c
1d þ 2d
1e þ 2e
Chx
Chx
Me(CH2)6
Me(CH2)6
Me(CH2)10
Cpe
1.0
2.0
1.0
2.0
2.0
2.0
1
1
2
1
2
1
4bb (74)
4bb (79)
4cc (52)
4cc (64)
4dd (58)
4ee (78)
a) All the reactions were carried out in H2O at r.t. with 100 mol-% of SDS (sodium dodecyl sulfate).
Molar ratio 1/2 1 : 1.5. b) Chx ¼ cyclohexyl, Cpe ¼ cyclopentyl. c) Yield of isolated products.
To confirm the above results, two aldehydes were treated competitively with a
single homoallyl alcohol (Scheme 6 and Table 4). It was shown again that the
nonaromatic surfactant is favored for the substrate having an unbranched alkyl
substituent. Namely, the proportion of 4cc over 4bc was obviously higher for the
reaction of 1c in SDS/HCl (Entries 7 and 8) than in DBSA (Entries 5 and 6), while only
a small surfactant effect was observed for the reaction of 1b (Entries 1 – 4). Similarly,
the proportion of 4cc over 4ce was higher for the reaction of 1c in SDS/HCl than in
DBSA (Entries 11 – 13), but not for 1e (Entries 9 and 10). Probably, the product ratio of
ca. 6 :4 is the ꢃoriginal valueꢀ for both 2b/2c and 2e/2c. The higher ratio in the DBSA-
promoted reaction of 1c (Entries 5, 6, and 11) can be rationalized by the inference that
the reaction 1c þ 2c was less favorable in DBSA, however, the reason is not clear as yet.
The result is consistent with the observation described for Table 1.
Scheme 6
a) See text and Table 4 for the conditions.
In conclusion, it was found that an alkyl-substituent effect is surely present in the
aqueous reaction of a homoallyl alcohol with an aldehyde (Yadavꢀs reaction system),
although the effect was not dramatic. The reaction proceeded smoothly for non-
conjugated aldehydes, and the compounds with structurally related substituents such as
Me(CH2)6 and Me(CH2)10, as well as cyclopentyl and cyclohexyl, showed similar

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Helvetica Chimica Acta – Vol. 92 (2009)
Table 4. Competition of Aldehydes Against Single Homoallyl Alcohola)
Entry Alcohol
Aldehydeb) Surfactant
Time [d] Yield [%]c) Ratio
1
2
3
4
5
6
7
8
9
10
11
12
13
1b (R ¼ Chx)
2b and 2c
2b and 2c
2b and 2c
2b and 2c
DBSAd)
1
1
1
1
2
2
2
1
1
1
2
2
1
63
64
54
61
54
39
56
58
59
68
35
37
50
4bb/4bc 62 : 38
4bb/4bc 62 : 38
4bb/4bc 58 : 42
4bb/4bc 57: 43
4bc/4cc 85 : 15
4bc/4cc 75 : 25
4bc/4cc 54 : 46
4bc/4cc 56 : 44
4ee/4ce 64 : 36
4ee/4ce 58 : 42
4ce/4cc 85 : 15
4ce/4cc 67: 33
4ce/4cc 64 : 36
1b (R ¼ Chx)
1b (R ¼ Chx)
1b (R ¼ Chx)
DBSAe)
SDS/HClf)
SDS/HClg)
DBSAd)
1c (R ¼ Me(CH2)6) 2b and 2c
1c (R ¼ Me(CH2)6) 2b and 2c
1c (R ¼ Me(CH2)6) 2b and 2c
1c (R ¼ Me(CH2)6) 2b and 2c
DBSAe)
SDS/HClf)
SDS/HClg)
DBSAd)
1e (R ¼ Cpe)
1e (R ¼ Cpe)
2e and 2c
2e and 2c
SDS/HClg)
DBSAd)
1c (R ¼ Me(CH2)6) 2e and 2c
1c (R ¼ Me(CH2)6) 2e and 2c
1c (R ¼ Me(CH2)6) 2e and 2c
SDS/HClf)
SDS/HClg)
a) All reactions were carried out in H2O at r.t. b) 1.2 Equiv. of each aldehyde was used. c) Yield of
f
isolated products. d) 100 mol-%. e) 200 mol-%. ) 100 mol-% of SDS with 1.0 equiv. of HCl. g) 100 mol-
% of SDS with 2.0 equiv. of HCl.
behavior, as expected. When both of the two reactants, the homoallyl alcohol and the
aldehyde, have an unbranched alkyl group, the reaction was more favorable in SDS/
HCl than in DBSA. These observations suggest that the structural similarity is a factor
determining the reactivity. We hope that the present results will be helpful in the
various studies of aqueous organic reactions.
Experimental Part
General. Anh. Na2SO4 was used for drying the extracted org. layers. Anal. TLC: precoated TLC
plates (silica gel 60 F254, layer thickness 0.2 mm). Column chromatography (CC): Wakogel C-200 or
Florisil (100 – 200 mesh). M.p.: Laboratory-Devices-Mel-Temp apparatus. IR Spectra: Jasco-FT/IR-230
1
1
spectrometer; ˜n in cmꢀ1. H- and 13C-NMR Spectra: Jeol-GSX-400 spectrometer; 400 MHz for H and
100 MHz for 13C; CDCl3 solns.; chemical shifts d in ppm with Me4Si (for 1H) or solvent (d (CDCl3) 77.00
for 13C) as internal standard, unless otherwise noted, J in Hz. EI-MS and HR-EI-MS: Jeol-SX-102A,
CMATE-II, or Shimadzu-GCMS-QP5050 mass spectrometer; in m/z (rel. %).
Preparation of the Substrates. Compound 1a is commercially available. Compounds 1b – 1e were
synthesized as follows. A soln. of commercial allylmagnesium chloride (3; 2.5 ml, 5 mmol; 2.0m in THF)
was diluted with dry Et2O (20 ml), and aldehyde 2 (5 mmol) was added at ꢀ 508. After being stirred for
4 h, the mixture was slowly warmed to r.t. overnight. Then, a sat. aq. NH4Cl soln. was added, the mixture
extracted with Et2O, the org. layer dried and concentrated, and the resultant oily residue subjected to CC
(SiO2) to afford homoallyl alcohols 1b – 1e.
Typical Procedure of Yadavꢀs Reaction. Aldehyde 2 (1.50 mmol) was added to a stirred mixture of
homoallyl alcohol 1 (1.00 mmol) and 4-dodecylbenzenesulfonic acid (1.00 mmol) in H2O (10 ml). After
being stirred at r.t. for 1 – 3 day(s) (see Tables 1 – 4), an aq. sat. NaHCO3 soln. was added, the mixture
extracted with Et2O, the org. layer dried and concentrated, and the residue purified by CC (SiO2) to
afford the product(s).
Compounds 4bc, 4be, 4bf, 4bg, 4bh, 4bi, and 4ce could not be isolated in pure form due to the
presence of inseparable by-product(s), and the following spectral data were obtained after partial
purification. Compounds 4aa [4], 4ab [4], and 4bb [6] were identified by comparison with the literature
data.

Helvetica Chimica Acta – Vol. 92 (2009)
1339
(2RS,4SR,6RS)-2-Heptyltetrahydro-6-phenyl-2H-pyran-4-ol (4ac): Colorless oil. IR (neat): 3383
(OH). 1H-NMR: 0.88 (t, J ¼ 6.9, 3 H); 1.21 – 1.72 (m, 14 H); 1.83 (br., OH); 2.02 (ddt, J ¼ 12.1, 4.6, 2.0,
1 H); 2.20 (ddt, J ¼ 12.1, 4.5, 2.1, 1 H); 3.44 – 3.51 (m, 1 H); 3.94 (tt, J ¼ 11.0, 4.6, 1 H); 4.35 (dd, J ¼ 11.5,
1.9, 1 H); 7.24 – 7.38 (m, 5 H). 13C-NMR: 14.10; 22.65; 25.48; 29.24; 29.62; 31.83; 36.04; 40.90; 42.98;
68.69; 76.01; 77.26; 125.87 (2C); 127.37; 128.32 (2C); 142.26. EI-MS: 276 (6, Mþ), 258 (5), 159 (33), 107
(100).
(2RS,4SR,6RS)-2-Cyclohexyl-6-heptyltetrahydro-2H-pyran-4-ol (4bc): Colorless oil. IR (neat): 3357
(OH). 1H-NMR: 0.88 (t, J ¼ 6.9, 3 H); 0.92 – 1.76 (m, 23 H); 1.88 – 2.01 (m, 4 H); 2.06 (br., OH); 2.89 –
2.98 (m, 1 H); 3.16 – 3.26 (m, 1 H); 3.74 (tt, J ¼ 11.0, 4.8, 1 H). 13C-NMR: 14.06; 22.61; 25.66; 25.98; 26.13;
26.55; 28.77; 29.24; 29.37; 29.48; 31.82; 36.06; 38.28; 41.53; 42.70; 68.81; 75.45; 79.93. EI-MS: 199 (36,
[M ꢀ cyclohexyl]þ), 183 (10), 155 (29), 139 (24), 41 (100). FAB-HR-MS: 283.2651 ([M þ H]þ,
C18H35Oþ2 ; calc. 283.2637).
(2RS,4SR,6RS)-2-Cyclohexyltetrahydro-6-undecyl-2H-pyran-4-ol (4bd): White solid. M.p. 53.5 –
55.58. IR (KBr): 3340 (OH). 1H-NMR: 0.88 (t, J ¼ 6.8, 3 H); 0.91 – 1.76 (m, 31 H); 1.88 – 2.01 (m,
4 H); 2.05 (br., OH); 2.89 – 2.98 (m, 1 H); 3.16 – 3.26 (m, 1 H); 3.75 (tt, J ¼ 11.0, 4.7, 1 H). 13C-NMR:
14.08; 22.65; 25.67; 25.99; 26.14; 26.56; 28.78; 29.32; 29.38; 29.52; 29.60 (3C); 29.63; 31.89; 36.06; 38.30;
41.55; 42.71; 68.85; 75.45; 79.93. EI-MS: 183 (28, [M ꢀ C11H23]þ), 165 (17), 139 (100). FAB-HR-MS:
339.3247 ([M þ H]þ, C22H43Oþ2 ; calc. 339.3263).
(2RS,4SR,6SR)-2-Cyclohexyl-6-cyclopentyltetrahydro-2H-pyran-4-ol (4be): White solid. M.p.
100.0 – 102.08. IR (KBr): 3294 (OH). 1H-NMR: 0.88 – 2.04 (m, 25 H); 2.90 – 3.00 (m, 2 H); 3.74 (tt,
J ¼ 10.9, 4.6, 1 H). 13C-NMR: 25.52; 25.62; 26.01; 26.18; 26.62; 28.95; 28.97; 29.35; 29.41; 38.55; 40.48;
42.78; 45.23; 69.05; 79.94; 80.03. EI-MS: 183 (18, [M ꢀ cyclopentyl]þ), 169 (15, [M ꢀ cyclohexyl]þ), 165
(9), 139 (54), 125 (100).
(2RS,4SR,6SR)-2-Cyclohexyl-6-(1-ethylpentyl)tetrahydro-2H-pyran-4-ol (4bf; 1:1 mixture of two
diastereoisomers). Colorless oil. IR (neat): 3338 (OH). 1H-NMR: 0.85 (t, J ¼ 6.8, 1.5 H, Me); 0.86 (t, J ¼
6.8, 1.5 H, Me); 0.89 (t, J ¼ 6.9, 3 H, Me); 0.93 – 1.48 (m, 16 H); 1.61 – 1.78 (m, 4 H); 1.90 – 1.98 (m, 4 H);
2.30 (br., OH); 2.90 – 2.99 (m, 1 H); 3.09 – 3.17 (m, 1 H); 3.75 (tt, J ¼ 10.9, 4.8, 1 H). 13C-NMR: 10.80;
11.41; 14.08; 14.13; 21.83; 22.28; 23.09; 23.20; 26.07 (2C); 26.20 (2C); 26.62 (2C); 28.65 (2C); 28.91; 28.93;
29.06; 29.08 (2C); 29.16; 38.29; 38.41; 38.45 (2C); 42.77; 42.80; 43.75; 44.06; 69.44 (2C); 77.08; 77.15;
79.84; 79.86. EI-MS: 199 (2, [M ꢀ cyclohexyl]þ), 183 (26, [M ꢀ Me(CH2)3CH(Et)]þ), 165 (15), 139
(100). FAB-HR-MS: 283.2594 ([M þ H]þ, C18H35O2þ ; calc. 283.2637).
(2RS,4SR,6SR)-2-(Cyclohex-1-en-1-yl)-6-cyclohexyltetrahydro-2H-pyran-4-ol (4bg): White solid.
M.p. 58.5 – 60.58. IR (neat): 3361 (OH). 1H-NMR: 0.80 – 2.28 (m, 24 H); 3.07 (ddd, J ¼ 11.2, 6.5, 1.4,
1 H); 3.58 (d, J ¼ 11.2, 1 H); 3.81 (tt, J ¼ 10.9, 4.7, 1 H); 5.69 (br. s, 1 H). 13C-NMR: 22.48; 22.61; 24.91;
25.24; 26.13; 26.19; 26.62; 28.56; 29.27; 37.88; 39.53; 42.73; 69.19; 78.59; 79.82; 121.86; 137.95. EI-MS: 264
(14, Mþ), 181 (2, [M ꢀ cyclohexyl]þ), 139 (66), 121 (100). HR-EI-MS: 264.2086 (Mþ, C17H28Oþ2 ; calc.
264.2089).
(2RS,4RS,6SR)-2-Cyclohexyltetrahydro-6-[(1E)-pent-1-en-1-yl]-2H-pyran-4-ol (4bh): Colorless oil.
IR (neat): 3365 (OH). 1H-NMR: 0.89 (t, J ¼ 7.2, 3 H); 0.90 – 2.04 (m, 20 H); 3.07 (ddd, J ¼ 11.1, 6.5, 1.3,
1 H); 3.70 – 3.76 (m, 1 H); 3.79 (tt, J ¼ 11.0, 4.7, 1 H); 5.50 (br. dd, J ¼ 15.3, 5.8, 1 H); 5.66 (br. dt, J ¼ 15.3,
6.5, 1 H). 13C-NMR: 13.70; 22.19; 26.11; 26.17; 26.57; 28.50; 29.44; 34.39; 37.68; 41.62; 42.66; 68.76; 75.91;
79.86; 130.46; 131.72. EI-MS: 183 (23, [M ꢀ PrCH¼CH]þ), 139 (79), 55 (100). HR-EI-MS: 252.2071
(Mþ, C16H28Oþ2 ; calc. 252.2089).
(2RS,4RS,6SR)-2-Cyclohexyltetrahydro-6-(2-methylprop-1-en-1-yl)-2H-pyran-4-ol (4bi): Yellow oil.
1
IR (neat): 3359 (OH). H-NMR: 0.88 – 1.49 (m, 11 H); 1.61 – 1.99 (m, 5 H); 1.67 (d, J ¼ 0.9, 3 H); 1.72
(br. s, 3 H); 3.06 (ddd, J ¼ 11.2, 6.6, 1.6, 1 H); 3.79 (tt, J ¼ 10.9, 4.7, 1 H); 3.96 (ddd, J ¼ 11.2, 7.5, 1.7, 1 H);
5.20 (d · sept., J ¼ 7.5, 1.2, 1 H). 13C-NMR: 18.43; 25.69; 26.05; 26.12; 26.54; 28.45; 29.50; 37.60; 41.61;
42.58; 68.70; 72.59; 79.91; 125.50; 136.28. EI-MS: 238 (3, Mþ), 139 (20), 41 (100). HR-EI-MS: 238.1947
(Mþ, C15H26Oþ2 ; calc. 238.1933).
(2RS,4SR,6RS)-2-Cyclohexyltetrahydro-6-(phenylmethyl)-2H-pyran-4-ol (4bj): White solid. M.p.
1
97.5 – 101.58. IR (KBr): 3303 (OH). H-NMR: 0.88 – 1.45 (m, 8 H); 1.62 – 1.75 (m, 5 H); 1.85 – 1.97 (m,
3 H); 2.67 (dd, J ¼ 13.5, 6.3, 1 H); 2.95 (dd, J ¼ 13.6, 6.5, 1 H); 2.99 (ddd, J ¼ 11.3, 6.7, 1.6, 1 H); 3.43 (ddt,
J ¼ 11.0, 1.7, 6.4, 1 H); 3.69 (tt, J ¼ 10.9, 4.7, 1 H); 7.17 – 7.29 (m, 5 H). 13C-NMR: 26.07; 26.17; 26.56; 28.76;

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Helvetica Chimica Acta – Vol. 92 (2009)
29.14; 37.96; 40.76; 42.44; 42.70; 68.71; 76.29; 79.88; 126.07; 128.08 (2C); 129.44 (2C); 138.59. EI-MS: 183
(48, [M ꢀ PhCH2]þ), 165 (14), 139 (100).
(2a,4a,6a)-2,6-Diheptyltetrahydro-2H-pyran-4-ol (4cc): White solid. M.p. 58.0 – 59.58. IR (KBr):
3460 (OH). 1H-NMR: 0.88 (t, J ¼ 6.8, 6 H); 1.12 (dt, J ¼ 12.2, 11.1, 2 H); 1.23 – 1.47 (m, 22 H); 1.53 – 1.60
(m, 2 H); 1.75 (br., OH); 1.93 (br. dd, J ¼ 12.0, 4.5, 2 H); 3.19 – 3.27 (m, 2 H); 3.77 (tt, J ¼ 10.9, 4.7, 1 H).
13C-NMR: 14.08 (2C); 22.64 (2C); 25.69 (2C); 29.28 (2C); 29.51 (2C); 31.82 (2C); 36.08 (2C); 41.43 (2C);
68.50; 75.53 (2C). EI-MS: 199 (55, [M ꢀ C7H15]þ), 181 (13), 163 (36), 41 (100).
(2RS,4SR,6SR)-2-Heptyltetrahydro-6-undecyl-2H-pyran-4-ol (4cd): White solid. M.p. 55.5 – 58.08.
IR (KBr): 3462 (OH). 1H-NMR: 0.88 (t, J ¼ 6.8, 6 H); 1.12 (dt, J ¼ 12.0, 11.2, 2 H); 1.23 – 1.45 (m, 30 H);
1.53 – 1.60 (m, 2 H); 1.85 (br., OH); 1.93 (dd, J ¼ 12.0, 4.5, 2 H); 3.19 – 3.26 (m, 2 H); 3.77 (tt, J ¼ 10.9, 4.8,
1 H). 13C-NMR: 14.08; 14.09; 22.64; 22.66; 25.68 (2C); 29.28; 29.34; 29.52; 29.56; 29.61 (3C); 29.66;
31.82; 31.90; 36.08 (2C); 41.42 (2C); 68.47; 75.54 (2C). EI-MS: 199 (44, [M ꢀ C11H23]þ), 181 (14), 163
(35), 55 (100).
(2RS,4SR,6RS)-2-Cyclopentyl-6-heptyltetrahydro-2H-pyran-4-ol (4ce): Colorless oil. IR (neat): 3348
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(OH). H-NMR: 0.88 (t, J ¼ 6.8, 3 H); 1.08 – 2.02 (m, 26 H); 2.94 – 3.01 (m, 1 H); 3.18 – 3.25 (m, 1 H);
3.76 (tt, J ¼ 10.9, 4.7, 1 H). 13C-NMR: 14.07; 22.63; 25.42; 25.51; 25.73; 28.92; 29.27; 29.47; 29.49; 31.82;
36.06; 40.30; 41.56; 45.16; 68.62; 75.48; 80.06. EI-MS: 199 (19, [M ꢀ cyclopentyl]þ), 181 (8), 169 (7, [M ꢀ
C7H15]þ), 163 (24), 81 (86), 41 (100).
(2a,4a,6a)-Tetrahydro-2,6-diundecyl-2H-pyran-4-ol (4dd): White solid. M.p. 79.0 – 80.58. IR (KBr):
1
3454 (OH). H-NMR: 0.88 (t, J ¼ 6.8, 6 H); 1.12 (q, J ¼ 11.3, 2 H); 1.23 – 1.45 (m, 39 H); 1.52 – 1.61 (m,
2 H); 1.94 (br. dd, J ¼ 12.0, 4.4, 2 H); 3.19 – 3.27 (m, 2 H); 3.78 (tt, J ¼ 10.9, 4.7, 1 H). 13C-NMR: 14.11
(2C); 22.68 (2C); 25.70 (2C); 29.35 (2C); 29.57 (2C); 29.62 (4C); 29.64 (2C); 29.67 (2C); 31,92 (2C);
36.09 (2C); 41.46 (2C); 68.54; 75.53 (2C). EI-MS: 255 (12, [M ꢀ C11H23]þ), 237 (5), 199 (27), 163 (20), 43
(100).
(2a,4a,6a)-2,6-Dicyclopentyltetrahydro-2H-pyran-4-ol (4ee): White solid. M.p. 118.5 – 120.08. IR
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(KBr): 3336 (OH). H-NMR: 1.13 (dt, J ¼ 12.3, 11.2, 2 H); 1.13 – 1.23 (m, 2 H); 1.35 – 1.73 (m, 13 H);
1.77 – 1.86 (m, 2 H); 1.89 (q, J ¼ 7.9, 2 H); 1.96 – 2.02 (m, 2 H); 2.97 (ddd, J ¼ 11.0, 7.9, 1.5, 2 H); 3.75 (tt,
J ¼ 11.0, 4.7, 1 H). 13C-NMR: 25.52 (2C); 25.63 (2C); 29.00 (2C); 29.42 (2C); 40.44 (2C); 45.18 (2C);
68.83; 80.01 (2C). EI-MS: 169 (16, [M ꢀ cyclopentyl]þ), 151 (6), 125 (100). HR-EI-MS: 238.1969 (Mþ,
C15H26Oþ2 ; calc. 238.1933).
Reaction of 2 and 5. Allyltrimethylsilane (5; 15 mmol) was added to a mixture of aldehyde 2
(5 mmol) and 4-dodecylbenzenesulfonic acid (5 mmol) in H2O (35 ml). After being stirred at r.t. for 3
weeks, the mixture was extracted with Et2O, the org. layer dried and concentrated, and the residue
purified by CC (SiO2) to give 4.
REFERENCES
[1] C.-J. Li, Chem. Rev. 1993, 93, 2023; C.-J. Li, L. Chen, Chem. Soc. Rev. 2006, 35, 68; U. F. Lindstrçm,
Chem. Rev. 2002, 102, 2751.
[2] R. Breslow, K. Groves, M. U. Mayer, Pure Appl. Chem. 1998, 70, 1933; R. Breslow, Acc. Chem. Res.
1991, 24, 159; U. M. Lindstrçm, F. Andersson, Angew. Chem., Int. Ed. 2006, 45, 548; S. Otto,
J. B. F. N. Engberts, Org. Biomol. Chem. 2003, 1, 2809.
[3] J. S. Yadav, B. V. S. Reddy, G. M. Kumar, C. V. S. R. Murthy, Tetrahedron Lett. 2001, 42, 89.
[4] J. S. Yadav, B. V. S. Reddy, K. C. Sekhar, D. Gunasekar, Synthesis 2001, 885.
[5] J. S. Yadav, B. V. S. Reddy, M. S. Reddy, N. Niranjan, J. Mol. Cat. 2004, 210, 99.
[6] J. S. Yadav, B. V. S. Reddy, G. G. K. S. N. Kumar, S. Aravind, Synthesis 2008, 395.
[7] B. B. Snider, in ꢃComprehensive Organic Synthesisꢀ, Ed. B. M. Trost, Pergamon Press, Oxford, 1991,
Vol. 2, p. 527.
[8] K. Manabe, S. Iimura, X.-M. Sun, S. Kobayashi, J. Am. Chem. Soc. 2002, 124, 11971.
[9] S. Shirakawa, S. Kobayashi, Org. Lett. 2007, 9, 311.
[10] A. Saito, M. Takayama, A. Yamazaki, J. Numaguchi, Y. Hanzawa, Tetrahedron 2007, 63, 4039.
Received December 3, 2008