Efficient method for the preparation of pinacols derived from aromatic and aliphatic ketones by using low-valent titanium reagents in dichloromethane-pivalonitrile

Article abstract of DOI:10.1139/v00-010

The reductive coupling reaction of aldehydes and ketones, including unsymmetrical aliphatic ketones, proceeded smoothly to give the corresponding pinacols in good to high yields under mild conditions by using combination of titanium(II) chloride and zinc or titanium(IV) chloride and zinc in dichloromethane-pivalonitrile. Meso-selective formation of the coupling products was observed in the cases of some aliphatic ketones. The diastereoselectivities of coupling products depend on both difference of bulkiness of 2-, and 2'-substituents of carbonyl group of the reactant, and overall steric effect around the carbonyl groups.

Full text of DOI:10.1139/v00-010

657
Abstract: The reductive coupling reaction of aldehydes and ketones, including unsymmetrical aliphatic ketones, pro-
ceeded smoothly to give the corresponding pinacols in good to high yields under mild conditions by using combination
of titanium(II) chloride and zinc or titanium(IV) chloride and zinc in dichloromethane–pivalonitrile. Meso-selective for-
mation of the coupling products was observed in the cases of some aliphatic ketones. The diastereoselectivities of cou-
pling products depend on both difference of bulkiness of 2-, and 2′-substituents of carbonyl group of the reactant, and
overall steric effect around the carbonyl groups.
Key words: diastereoselective pinacol reaction, dichloromethane-pivalonitrile, titanium(II) chloride, titanium(IV) chloride,
zinc.
Résumé : La réaction de couplage réducteur d’aldéhydes ou des cétones, y compris des cétones aliphatiques non
symétriques, se produit facilement et elle conduit aux pinacols correspondants avec des rendements allant de bons à
élevés, dans des conditions douces, en opérant dans un mélange de dichlorométhane et de pivalonitrile en présence de
zinc et de chlorure de titane(II) ou de chlorure de titane(IV). On a observé une formation sélective de l’isomère méso
dans les cas de quelques cétones aliphatiques. Les diastéréosélectivités des produits de couplage dépendent de la
différence de taille des substituants en positions 2 et 2′ par rapport au groupe carbonyle qui réagit ainsi que de l’effet
stérique global autour des groupes carbonyles.
Mots clés : réaction pinacolique diastéréosélective, dichlorométhane-pivalonitrile, chlorure de titane(II), chlorure de
titane(IV), zinc.
[Traduit par la Rédaction] Kagayama et al. 665
the combination of TiCl3 and Mg for the generation of ac-
tive low-valent species. McMurry and co-workers studied
The reductive coupling of carbonyl compounds using low-
this coupling reaction in detail by using either TiCl3 and
valent metal species has been known as pinacol coupling re-
action since last century. In 1973, two research groups,
LiAlH4, or TiCl3 and Zn-Cu from 1974 (1c). The coupling
reactions using other transition metals as a reducing reagent
Mukaiyama (1a) and Tyrlik (1b), independently reported this
have been extensively studied in this decade (2).
coupling reaction and its subsequent deoxygenation reaction
Concerning intermolecular type pinacol reactions, recent
topics are directed to investigate the formation of C2 or S2
symmetric homocoupling products with high diastereoselec-
tivities (dl or meso) under mild conditions. In the cases of
that afforded olefin with low-valent titanium species. In the
above two methods, the former used either combination of
TiCl4 and Zn, or TiCl4 and LiAlH4, and the latter employed
aromatic aldehydes, for example, the corresponding homo-
coupling products were afforded with high dl-selectivities
Received August 12, 1999. Published on the NRC Research
Press website on May 19, 2000.
when several kinds of low-valent metals such as Ti (3), Sm
(4), and Nb (5) were used.2 Further, it was recently reported
This paper is dedicated to Professor Stephan Hanessian on
the occasion of his 65th birthday in recognition of his
significant contributions to the art of organic synthesis.
that dl-homocoupling product was preferentially formed
from acetophenone by the combined use of a TiCl3–Mg–
catechol system (7).
A. Kagayama, K. Igarashi, and T. Mukaiyama.1
Department of Applied Chemistry, Faculty of Science,
Science University of Tokyo, Kagurazaka, Shinjuku-ku,
Tokyo 162–8601, Japan.
This dl-selection was explained by assuming the genera-
tion of intermediate radical species as sketched in Scheme 1,
in which oxygen atoms of two ketyl radicals are placed side
by side and phenyl groups are arranged anti to each other to
minimize the steric interaction when these ketyl radicals ap-
proach each other. The location of two oxygen atoms was
controlled by the interaction between metal on the ketyl rad-
ical and oxygen atom of the other ketyl radical, and (or)
1Author to whom correspondence may be addressed.
Telephone: +81-3-3260-4271. Fax: +81-3-3235-2214.
e-mail: mukaiyam@rs.kagu.sut.ac.jp.
2Stereoselective pinacol coupling reactions using a catalytic
amount of low-valent metal were recently reported; see ref 6.
Can. J. Chem. 78: 657–665 (2000)
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658
Can. J. Chem. Vol. 78, 2000
Scheme 1.
bridged two metal atoms. However, there has been no
systematic study on relationship between the diastereoselec-
tivities of coupling products and the steric effects of
substituents at 2- and 2′-positions of carbonyl group of the
reactants.
To investigate this subject, it is appropriate to examine the
coupling reaction of unsymmetrical aliphatic ketones; how-
ever, in this reductive coupling, the reactivities of aliphatic
ketones are generally low and the required severe reaction
conditions cause pinacol rearrangement or deoxygenation of
the initially produced pinacol to form the corresponding olefins.
Recently, we found that pinacol coupling reaction of
aliphatic ketones proceeded smoothly in dichloromethane–
pivalonitrile by using the combination of titanium(II) chlo-
ride and zinc at room temperature (8). Further, usefulness of
TiCl2 was demonstrated in the following experiment, i.e., in
our total synthesis of antitumor agent Taxol (9), construction
of the A ring onto the BC ring system was performed by
intramolecular pinacol coupling reaction using low-valent ti-
tanium species prepared in situ from TiCl2–LiAlH4. Though
a similar reaction was observed by the combined use of
TiCl3–LiAlH4, the generation of low-valent titanium species
took place in less acidic media when the former combination
was employed. The titanium(II) reagent, TiCl2, is facilely
prepared from TiCl4 and hexamethyldisilane according to
the reported procedure (10), and it can be stored under argon
atmosphere for a long time.3 In this article, we would like to
describe the relationship between the diastereoselectivities of
coupling products and the steric effects of substituents at 2-,
and 2′-positions of carbonyl group of the reactants in the
pinacol coupling reaction by using TiCl2 and Zn. The results
obtained by further examination of this type of coupling re-
action using a combination of TiCl4 and Zn are also dis-
cussed herein.
cially pivalonitrile, accelerated this reaction to give the
pinacol in 63% yield by using 2 molar equivalents of TiCl2
and Zn. Finally, it was found that the yield was improved up
to 87% when 2 molar equivalents of TiCl2 were gradually
added to the reaction mixture for the duration of the 6 h pe-
riod in the presence of Zn and pivalonitrile at room tempera-
ture. When acetonitrile or o-methoxybenzonitrile was used
as a co-solvent in the above reaction, the corresponding
pinacol was obtained in 78 or 52% yield, respectively.
Fürstner and Hupperts demonstrated the beneficial effect of
a cyano function tethered to a chlorosilane on the reductive
coupling reaction using a catalytic amount of TiCl3–Zn–
chlorosilane system in their indole synthesis reaction (15).
These results indicate that nitriles moderately coordinate
to the low-valent titanium species to form the active com-
plexes, which helps both the solvation of the titanium parti-
cles and electron donation of the titanium complex to the
carbonyl compounds.4,5 On the other hand, other additives
(pyridine, HMPA, and 2-methyloxazoline) coordinate too
strongly to the low-valent titanium species, which result in
the decreased reactivities.
Yields and diastereoselectivities of the pinacol coupling
reactions using several ketones and aldehydes are summa-
rized in Table 1. Aromatic ketones were transformed to the
corresponding pinacols in high yields with dl-selectivies
(Entries 1–5) though the selectivity in case of acetophenone
was rather low in comparison with the reported one (7). This
dl-selectivity increased either when electron-donating group
substituted benzaldehyde derivatives or carbonyl compound
with bulky group at the 2-position were used, that is, the
diastereoselectivity came up kinetically. This consideration
may be supported by the results that no diastereoselectivity
was observed in the case of highly reactive benzaldehyde
while moderate selectivity was observed in the reaction of
less reactive 3-phenylpropanal (Entries 11 and 12).
Acetophenone was reductively coupled by using TiCl2 and
Zn in THF at 0°C to give 2,3-diphenyl-2,3-butanediol in
93% yield (dl:meso = 76:24) while 4-phenyl-2-butanone did
not react under the same reaction conditions. Porta et al. re-
ported that TiCl3 could reduce benzaldehyde in dichloro-
methane to afford the corresponding pinacol though the
same reaction did not proceed in THF which is commonly
employed solvent in these reactions (3b). Actually, 4-phenyl-
2-butanone was reductively coupled by using the combina-
tion of TiCl2–Zn in dichloromethane and the desirable
pinacol was obtained in 23% yield and 65% of the 4-phenyl-
2-butanone was recovered.
Although several additives such as pyridine (12) and
HMPA (13) used to be known effective in this coupling reac-
tion, these two additives and 2-methyloxazoline were not ef-
fective for the present reaction when the combination of
TiCl2 and Zn system was used (0, 0, and 13% yields, respec-
tively). On the other hand, it was found that nitriles, espe-
In the reactions of aliphatic ketones (Entries 6–10), the
corresponding pinacols were obtained in good to high yields
except for 3,3-dimethyl-2-butanone. The diastereoselectivity
was not observed when 4-phenyl-2-butanone was used as a
substrate that has a set of methyl and methylene groups at-
tached to 2- and 2′-positions of carbonyl group of the reac-
tant (Entry 6). On the other hand, the meso-selective reaction
took place when substrates that have two dimensionally
different substituents, i.e., the respective combination of
3 A few types of titanium(II) chloride complexes were used for pinacol coupling reactions, which were carried out only in ethers such as
TiCl2·LiCl (11a) or TiCl2(thf)2·xLiCl (11b).
4 Actually, on 13C NMR spectra, signals of pivalonitrile (δ: 27.5, 27.8 and 125.3 ppm) shifted and broadened (δ: 24.8, 31.0 and 131.3 ppm) by
addition of 1/3 molar equivalent of TiCl2 in chloroform-d at room temperature. This result indicates the formation of coordinated complex.
5 Structural data on the coordination of nitriles onto low-valent titanium are shown in ref 14. Fowles and Lester reported the structure of iso-
lated polymeric titanium(II) complexes as TiX2·2CH3CN (14b).
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Kagayama et al.
659
Table 1. Yields and selectivities of the formation of pinacols from various ketones and aldehydes.
methyl and methyne (Entries 7 and 8), or methylene and
methyne (Entry 9) groups, were used.
McMurry and Siemers studied intramolecular pinacol
coupling reaction of several dialdehydes, in which the rela-
tionship between the diastereoselectivities and the ring num-
ber of products was examined in detail (16). In the pres-
ent experiment, two types of diketones were examined (Ta-
ble 2), and the selectivity decreased a little in the case of
aliphatic diketone while aromatic diketone reacted in perfect
cis-selective manner. It suggested that the interaction
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660
Can. J. Chem. Vol. 78, 2000
Table 2. Yields and selectivities of the formation of 1,2-cyclohexanediol derivatives from diketones.
Table 3. Yields and selectivities of pinacol coupling reactions without using zinc metal.a
between Ti and oxygen would be rather weak in the case of
aliphatic ketone than that of aromatic ketone.
Scheme 2.
Ti-O interaction
Ti Ti
Benzaldehyde and acetophenone were reductively coupled
by using TiCl2 in the absence of Zn (Table 3). Though the
R1
Ar
HO
Ar
R1
yields were rather low, dl-selectivities became very much
higher than those of the reaction when a TiCl2–Zn system
was applied. These results may be explained by considering
the kinetic effect and the Lewis acidity of titanium species
which may also influence the above diastereoselectivities
(see Scheme 1). The higher-valent metal behaved as a stron-
ger Lewis acid compared with the lower-valent one, so that,
in the absence of Zn, the Ti(III) atom on the ketyl radical
(formed from TiCl2 and the carbonyl compound) is coordi-
nated more strongly to build a Ti-bridging intermediate (3b)
(17) compared with Ti(I) (or Ti(II)) atom on the ketyl radical
existed in the reaction using the TiCl2–Zn system.
O
O
aromatic ketones
R1
· ·
R1
OH
Ar
R1
Ar
dl selective
A
2
O
·
R2
stable intermediate
Ti
+
TiCl2 + Zn
R1
R1
R2
O
R2
HO
·
R2
·
R2
R1
OH
aliphatic ketones
R1
O
Ti
meso selective
B
From these results, the mechanism of diastereoselection in
the present reaction may be explained as shown in
Scheme 2. When isobutyrophenone is used, the generated
ketyl radical species form an intermediate Ti-bridging com-
plex A, which is in turn connected to dl-products. When
other aromatic ketones are used, more highly reactive ketyl
radicals would be generated because these compounds are
less hindered compared to isobutyrophenone. Therefore,
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Kagayama et al.
661
Table 4. Pinacol coupling reaction of ketones by using combinations of equimolar amounts of TiClx and Zn.
other pathways to be connected to meso-products can be
assumed to exist in addition to that mentioned above and
relatively lower stereoselectivities were observed. On the
other hand, in the cases of aliphatic ketones, the highly sym-
metrical intermediate B, a pair of two ketyl radicals, is
formed to preferentially produce meso-pinacol because these
radical species would be relatively unstable and the interac-
tion between titanium and oxygen atoms in the intermediate
would be rather weak.
It is noted that the selectivity depends on the difference of
bulkiness of the 2- and 2′-substituents of the carbonyl group
of the reactants and the overall steric interaction around the
carbonyl group.
Application of TiCl4 instead of TiCl2 was studied in this
type of reaction in dichloromethane–pivalonitrile. So far
many kinds of low-valent titanium reagents have been gener-
ated from TiCl3 rather than from TiCl4 because the latter is
coordinated so strongly by THF which has been generally
considered as the most effective solvent for reductive cou-
pling reaction. Concerning the reaction using low-valernt ti-
tanium reagent generated from TiCl4 and Zn in THF,
Mukaiyama et al. reported that aliphatic aldehydes or ke-
tones were reduced to give the corresponding pinacols at
rather high temperatures (1a). Therefore, it was considered
that the highly active low-valent titanium species giving the
corresponding olefin could only be generated from TiCl3.
Since the present reaction proceeded at room temperature
in dichloromethane–pivalonitrile by using the TiCl2–Zn sys-
tem, the similar reactions using TiCl3 or TiCl4 were also
tried under the same reaction conditions. While a system
(TiCl3 and 1.5 equivalents Zn) in dichloromethane–pivalo-
nitrile did not reduce the 4-phenyl-2-butanone, a system
(TiCl4 and 2 equivalents Zn) produced the desired coupling
product in 86% yield.
Titanium(IV) chloride did not react with Zn in dichloro-
methane solvent; however, the addition of pivalonitrile to
this mixture induced the generation of low-valent titanium
species in which the gray suspension turned to dark blue,
and then to dark brown. On the other hand, when acetonitrile
was used as a co-solvent, the mixture of generated low-
valent titanium species was not homogeneous and the yield
of pinacol originated from 4-phenyl-2-butanone decreased to
24%. These results indicate that pivalonitorile would in-
crease the solubility of generated low-valent titanium species
by forming a soluble complex and the polarity of the reac-
tion media to help both electron-transfer reaction.6
The yields and diastereoselectivities of the pinacols formed
from several ketones by using TiCl4–Zn are summarized in
6 It is generally known that the nitriles are one of the most popular solvents for the electrochemical studies
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Can. J. Chem. Vol. 78, 2000
Table 4, together with the results using TiCl2–Zn. These re-
actions employing equimolar amount of TiCl4 proceeded
smoothly to give several coupling products of aliphatic ke-
tones in high yields except 3,3-dimethyl-2-butanone. Since
the generated low-valent titanium species from TiCl4 was
more soluble in the above solvent, results obtained here
were better than those using TiCl2.
added dropwise. Once TLC analysis indicated that all of the
ketone had been consumed (<16 h), saturated aqueous
NH4Cl was added to the reaction mixture. The reaction mix-
ture was filtered, and the filtrate was separated. The aqueous
portion was extracted with CH2Cl2 (4 mL × 3), and com-
bined organic layers were washed successively with a satu-
rated aqueous NaHCO3 and brine, and dried over Na2SO4,
filtered, and concentrated. The crude product was subjected
to thin-layer chromatography (hexane – ethyl acetate) to af-
ford the desired pinacol (56 mg, 93%).
The reductive coupling reactions of various ketones and
aldehydes including aliphatic unsymmetrical ketones pro-
ceeded under mild conditions by using TiCl2–Zn or TiCl4–
Zn in dichloromethane–pivalonitrile. It was also shown that
the diastereoselectivities of coupling products depend not
only on the difference of bulkiness of 2-, and 2′-substituents
of carbonyl group of the reactants, but also on overall steric
effect around the carbonyl groups.
Method B
To a gray suspension of activated Zn powder (65 mg,
1 mmol) and BuCN (0.44 mL, 4 mmol) in CH2Cl2 (2.5 mL)
t
was added a solution of 4-phenyl-2-butanone (74 mg,
0.5 mmol) in CH2Cl2 (1.3 mL). After stirring for 30 min,
TiCl2 (119 mg, 1 mmol) was added gradually (divided in 6
times at interval of 1 h) under argon by powder inlet
equipped to the reaction apparatus. The resulting mixture
was stirred for an additional 1 h, and then saturated aqueous
NH4Cl was added. The same work up as method A gave the
desired pinacol (65 mg, 87%).
General
Typical procedure for the reductive coupling reaction of
ketones using titanium(IV) chloride and zinc in dichloro-
methane with pivalonitrile
Melting points were recorded on a Yanaco MP-S3 micro
melting point apparatus. Elemental analyses were performed
by MC Research Center Inc. FT-IR spectra were recorded on
1
a Horiba FT-300 infrared spectrometer. H- and 13C NMR
To a gray suspension of TiCl4 (95 mg, 0.5 mmol) and acti-
vated Zn powder (65 mg, 1 mmol) in CH2Cl2 (2.5 mL) was
spectra were recorded on a JEOL JNM-EX270L, a JEOL
JNM-LA400, and a JEOL JNM-LA500 spectrometer using
tetramethylsilane (TMS) or chloroform-d (CDCl3) as internal
standard. The following abbreviations are used: s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet, and br =
broad. High-resolution mass spectra were recorded on a
JEOL JMS-SX102A instrument with 4-nitrobenzyl alcohol
as a matrix. Thin layer chromatography used routinely for
purification and separation of product mixtures was per-
formed on Wakogel B5F. Analytical thin layer chromatogra-
phy was performed using E. Merck 0.25 mm silica gel 60
F254 plates, and visualization was accomplished with
ethanolic phosphomolybdic acid. All reactions were carried
out under argon atmosphere in dried glassware. Dichloro-
methane and pivalonitrile were distilled from diphosphorus
pentoxide, then calcium hydride, and dried over MS 4A. All
substrates were purchased from Tokyo Kasei Kogyo, Kanto
Chemical, Aldrich Chemical, or Merck. Ketones and alde-
hydes were used after purification by distillation. 1,4-
Dibenzoylbutane and 2,6-octanedione were used as received.
Titanium(II) chloride was prepared by Nalura’s procedure
(9). Anal. calcd. for TiCl2: Ti 40.31, Cl 59.69; found: Ti
39.89, Cl 59.28. Zinc powder (Kanto Chemical) was acti-
vated by 1 N HCl, washed with distilled water and ether suc-
cessively, and dried in vacuo.
t
added BuCN (0.22 mL, 2 mmol) dropwise. After the result-
ing dark brown suspension was stirred for 30 min, a solution
of 4-phenyl-2-butanone (74 mg, 0.5 mmol) in CH2Cl2
(1.3 mL) was added. The reaction mixture was stirred for
16 h at room temperature and then saturated aqueous NH4Cl
was added. The same work up as above procedure gave the
desired pinacol (64 mg, 86%).
Diastereoselectivities of pinacols
400 MHz H NMR spectra assignments were used for the
determination of the dl:meso ratio of the crude pinacols ob-
tained.
1
meso- and dl-2,3-Diphenyl-2,3-butanediol (18): Colorless
1
solid; H NMR (CDCl3) δ: 1.48 (6H, s, CH3, dl), 1.57(6H, s,
CH3, meso), 2.36 (2H, br, OH, meso), 2.63 (2H, br, OH, dl),
7.24–7.15 (20H, m, Ph-H). Assignments were made by com-
paring the relative heights of methyl signals at δ 1.48 and δ
1.57, respectively.
meso- and dl-2,3-Bis(4-methoxyphenyl)-2,3-butanediol (17):
Colorless solid; H NMR (CDCl3) δ: 1.45 (6H, s, CH3, dl),
1.54 (6H, s, CH3, meso), 2.35 (2H, br, OH, meso), 2.64 (2H,
br, OH, dl), 3.78 (6H, s, OCH3, meso), 3.79 (6H, s, OCH3,
dl), 6.75–7.11 (16H, m, Ph-H). Assignments were made by
comparing the relative heights of methyl signals at δ 1.45
and δ 1.54, respectively.
1
Typical procedure for the reductive titanium(II)
chloride and zinc in dichloromethane with pivalonitrile:
Method A
meso- and dl-2,3-Bis(4-bromophenyl)-2,3-butanediol (17):
Colorless solid; H NMR (CDCl3) δ: 1.45 (6H, s, CH3, dl),
1.53 (6H, s, CH3, meso), 2.28 (2H, br, OH, meso), 2.60 (2H,
br, OH, dl), 7.02–7.36 (16H, m, Ph-H). Assignments were
made by comparing the relative heights of methyl signals at
δ 1.45 and δ 1.53, respectively.
1
To a suspension of TiCl2 (59 mg, 0.5 mmol) and activated
Zn powder (32 mg, 0.5 mmol) in CH2Cl2 (2.5 mL) was
t
added BuCN (0.22 mL, 2 mmol). After the resulting dark
brown suspension was cooled to 0°C, a solution of
acetophenone (60 mg, 0.5 mmol) in CH2Cl2 (1.3 mL) was
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Kagayama et al.
663
meso- and dl-3,4-Diphenyl-3,4-hexanediol (19): Colorless
solid; H NMR (CDCl3) δ: 0.59 (6H, dd, J = 7.3, 7.3 Hz,
13.1 Hz, 2H, CH2), 1.99 (ddd, J = 4.1, 4.4, 13.1 Hz, 2H,
CH2), 2.70 (ddd, J = 4.4, 5.1, 13.1 Hz, 2H, CH2), 2.81 (ddd,
J = 4.1, 4.9 Hz, 2H, CH2), 7.07–7.35 (10H, m, Ph-H); 13C
NMR (CDCl3) δ: 19.5, 29.6, 29.8, 30.4, 38.1, 38.9, 84.7,
106.7, 125.8, 128.3, 128.4, 142.5; HRMS ([M + Na]+): calcd
for C23H30O2Na: 361.2144; found: 361.2113.
1
CH3, meso), 0.60 (6H, dd, J = 7.3, 7.3 Hz, CH3), 1.59 (2H,
dq, J = 7.3, 14.3 Hz, CH2, meso), 1.71 (2H, dq, J = 7.3,
14.3Hz, CH2), 2.07 (2H, dq, J = 7.3, 14.3Hz, CH2), 2.13
(2H, br, OH, meso), 2.60 (2H, br, OH), 2.27 (2H, dq, J =
7.3, 14.3 Hz, CH2, meso), 7.28–7.15 (20H, m, Ph-H). As-
signments were made by comparing the relative areas of
methylene signals at δ 1.71 and δ 1.59, respectively.
meso- and dl-2,3,4,5-Tetramethyl-3,4-hexanediol (20): Col-
orless oil. Anal. calcd. for C10H22O2: C 68.92, H 12.72;
found: C 69.30, H 12.30. Assignments were made by com-
paring the relative heights of methyl signals at δ 1.14 and δ
1.15, respectively. Separation of the pure isomers from crude
reaction mixture was achieved by benzylidene protection,7
thin-layer chromatography (hexane – ethyl acetate), and
cleavage of the protecting group as described below.
meso- and dl-2,5-Dimethyl-3,4-diphenyl-3,4-hexanediol (19):
Colorless solid; 1H NMR (CDCl3) δ: 0.39 (6H, d, J =
6.9 Hz, CH3, dl), 0.67 (6H, d, J = 6.9 Hz, CH3, meso), 0.75
(6H, d, J = 6.6 Hz, CH3, meso), 1.22 (6H, d, J = 6.3 Hz,
CH3, dl), 1.78 (2H, sep, J = 6.6 Hz, CH, dl), 2.30 (2H, sep, J
= 6.9 Hz, CH, meso), 2.84 (2H, s, OH, dl), 2.95 (2H, s, OH,
meso), 7.45–7.23 (20H, m, Ph-H). Assignments were made
by comparing the relative areas of methyl signals at δ 0.39
and δ 0.67, respectively.
(4RS,5RS)- and (2R,4RS,5SR)-4,5-Diisopropyl-4,5-dimethy-
2-phenyl-1,3-dioxolane: To a solution of meso- and dl-2,3,4,5-
tetramethyl-3,4-hexanediol (50 mg, 0.29 mmol) in CH2Cl2
(2 mL) and α ,α -dimethoxytoluene (175 mg, 1.2 mmol) at
0°C was added CSA (35 mg, 0.15 mmol). After the reaction
mixture had been stirred for 16 h at room temperature,
triethylamine (0.5 mL) was added. After evaporation of the
solvent, the crude product was purified by the thin-layer
chromatography to afford (4RS,5RS)- and (2R,4RS,5SR)8-
4,5-diisopropyl-4,5-dimethy-2-phenyl-1,3-dioxolane.
meso- and dl-3,4-Dimethyl-1,6-diphenyl-3,4-hexanediol (6a):
Colorless oil; IR (neat) ν: 3432, 3024, 2954, 2924, 1604,
1496, 1450, 1373, 1111, 1056, 949, 748, 702 cm–1; 1H NMR
(CDCl3) δ: 1.25 (6H, s, CH3), 1.28 (6H, s, CH3), 1.64–1.74
(4H, m, CH2), 1.87–1.98 (4H, m, CH2), 2.05 (4H, br, OH),
2.64–2.72 (4H, m, CH2), 2.76–2.85 (4h, m, CH2), 7.15–7.30
(20H, m, Ph-H); 13C NMR (CDCl3) δ: 20.8, 21.1, 30.2, 30.3,
38.2, 38.5, 76.98, 125.7, 128.1, 128.37, 128.40, 142.6,
(4RS,5RS)-Isomer (27 mg, 36%): Colorless oil; IR (neat) ν:
3062, 2970, 2877, 1466, 1381, 1219, 1095, 1026, 895,
142.7; HRMS ([M
+
Na]+): calcd for C20H26O2Na:
1
702 cm–1; H NMR (CDCl3) δ: 0.91 (3H, d, J = 7.0 Hz,
321.1831; found: 321.1847. Diastereomeric ratio (50:50)
was determined from the two equivalent methyl signals at
CH3) 0.93 (3H, d, J = 7.0 Hz, CH3), 0.95 (3H, d, J = 6.6 Hz,
CH3), 1.07 (3H, d, J = 6.6 Hz, CH3), 1.22 (3H, s, CH3), 1.25
(3H, s, CH3), 2.15 (1H, qq, J = 7.0, 6.6 Hz, CH), 2.26 (1H,
qq, J = 7.0, 6.6 Hz, CH), 5.85 (1H, s, CHPh), 7.30–7.37
(3H, m, Ph-H), 7.46–7.49 (2H, m, Ph-H); 13C NMR (CDCl3)
δ: 13.3, 15.9, 19.1, 19.2, 19.5, 19.8, 31.5, 32.9, 88.1, 88.2,
98.6, 126.5, 128.1, 128.5, 139.9; HRMS ([M + Na]+): calcd
for C17H26O2Na: 285.1831; found: 285.1872.
1
1.25 and δ 1.28 in the H NMR spectrum of the crude prod-
uct. It was supported that almost equivalent amounts of two
isomers of 2,2-dimethyl-1,3-dioxolane derivatives were ob-
tained from acetonide protection described below.
cis- and trans-2,2-Dimethyl-4,5-bis(3-phenylethyl)-1,3-dioxolane:
To a solution of meso- and dl-3,4-Dimethyl-1,6-diphenyl-
3,4-hexanediol (50 mg, 0.17 mmol) in CH2Cl2 (2 mL) and
2,2-dimethoxypropane (4 mL) at 0°C was added CSA
(28 mg, 0.12 mmol). After the reaction mixture had been
stirred for 16 h at room temperature, triethylamine (0.3 mL)
was added. After evaporation of the solvent, the thin-layer
chromatography to afford cis- and trans-2,2-dimethyl-4,5-
bis(3-phenylethyl)-1,3-dioxolane. cis-Isomer (26 mg, 45%):
colorless oil; IR (neat) ν: 3062, 2993, 2939, 2870, 1604,
1496, 1458, 1373, 1211, 1111, 1065, 1011, 895, 841, 748,
(2R,4RS,5SR)-Isomer (16 mg, 21%): Colorless oil; IR (neat)
ν: 3060, 2978, 2877, 1458, 1381, 1219, 925, 864, 725 cm–1;
1H NMR (CDCl3) δ: 0.90 (6H, d, J = 6.1 Hz, CH3), 0.92
(6H, d, J = 6.2 Hz, CH3), 1.22 (6H, s, CH3), 2.17 (2H, qq, J
= 6.1, 6.2 Hz, CH), 5.93 (1H, s, CHPh), 7.29–7.36 (3H, m,
Ph-H), 7.48 (2H, m, Ph-H); 13C NMR (CDCl3) δ: 14.9, 19.1,
19.6, 31.3, 87.8, 98.6, 126.1, 128.0, 128.1, 140.0; HRMS
([M + Na]+): calcd for C17H26O2Na: 285.1831; found:
285.1799.
1
701, 517 cm–1; H NMR (CDCl3) δ: 1.29 (6H, s, CH3), 1.54
(6H, s, CH3), 1.64 (2H, ddd, J = 4.9, 5.0, 13.1 Hz, CH2),
2.11 (2H, ddd, J = 4.2, 4.2, 13.1 Hz, CH2), 2.73 (2H, ddd, J
= 4.2, 5.0, 13.2 Hz, CH2), 2.87 (2H, ddd, J = 4.2, 4.9,
13.2 Hz, CH2), 7.20–7.37 (10H, m, Ph-H); 13C NMR
(CDCl3) δ: 19.5, 29.6, 30.2, 38.9, 84.7, 106.6, 125.8, 128.3,
128.4, 142.7; HRMS ([M + Na]+): calcd for C23H30O2Na:
361.2144; found: 361.2158. trans-Isomer (24 mg, 42%): col-
orless oil; IR (neat) ν: 3062, 2985, 2939, 2870, 1743, 1604,
1496, 1458, 1373, 1219, 1180, 1065, 1011, 895, 841, 748,
dl-2,3,4,5-Tetramethyl-3,4-hexanediol: To a solution of
(4RS,5RS)-4,5-diisopropyl-4,5-dimethyl-2-phenyl-1,3-dioxolane
(27 mg, 0.10 mmol) in EtOH (2 mL) was added Pd(OH)2
(14 mg, 0.10 mmol) under an argon atmosphere. Hydrogen
gas was purged through the mixture and stirred for 1 h. The
reaction mixture was filtered and evaporated. Thin-layer
chromatography afforded dl-2,3,4,5-tetramethyl-3,4-hexanediol
(17 mg, 0.097 mmol, 97%). Colorless solid; mp 45–47°C;
IR (neat) ν: 3471, 2993, 2962, 2915, 1466, 1381, 1173,
1
1
701, 525 cm–1; H NMR (CDCl3) δ: 1.33 (6H, s, CH3), 1.49
1118, 1072, 1018, 918, 887, 594 cm–1; H NMR (CDCl3) δ:
(3H, s, CH3), 1.51 (3H, s, CH3), 1.57 (ddd, J = 4.9, 5.1,
0.99 (6H, d, J = 6.7 Hz, CH3), 1.00 (6H, d, J = 6.4 Hz,
7 The acetonide protection for 2,3,4,5-tetramethyl-3,4-hexanediol was tried, but the corresponding 2,2-dimethyl-1,3-dioxolane derivatives
were not obtained at all.
© 2000 NRC Canada

664
Can. J. Chem. Vol. 78, 2000
CH3), 1.15 (6H, s, CH3), 1.75 (2H, br, OH), 2.09 (2H, qq, J
= 6.7, 6.4 Hz, CH); 13C NMR (CDCl3) δ: 18.7, 19.1, 19.8,
33.7, 79.1. Anal. calcd. for C10H22O2: C 68.92, H 12.72;
found: C 68.88, H 12.71.
found: 277.2052. Anal. calcd. for C16H30O2: C 75.54, H
11.89; found: C 75.45, H 11.91.
meso-2,3-Dicyclohexyl-2,3-butanediol (20): This isomer was
obtained from (2R,4RS,5SR)-4,5-dicyclohexyl-4,5-dimethy-
2-phenyl-1,3-dioxolane in 99% yield. Colorless solid; mp
118–119°C (lit. 124°C); IR (KBr) ν: 3502, 2938, 2916,
2854, 1450, 1381, 1134, 1088, 1065, 995, 926, 895, 594,
meso-2,3,4,5-Tetramethyl-3,4-hexanediol: This isomer was
obtained from (2R,4RS,5SR)-4,5-diisopropyl-4,5-dimethy-2-
phenyl-1,3-dioxolane by the same procedure as the case of
dl -isomer in 92% yield. Colorless solid; mp 62–64°C; IR
(neat) ν: 3417, 2969, 2908, 1466, 1389, 1165, 1103, 1033,
1
532 cm–1; H NMR (CDCl3) δ: 1.06–1.31 (10H, m, CH2),
1.14 (6H, s, CH3), 1.58–1.79 (10H, m, CH2), 2.02- 2.05
(2H, m, CH), 2.28 (2H, br, OH); 13C NMR (CDCl3) δ: 21.4,
26.5, 26.9, 27.0, 28.2, 29.3, 44.0, 79.2; HRMS ([M + Na]+):
calcd for C16H30O2Na: 277.2143; found: 277.2079.
1
1003, 918, 895, 517 cm–1; H NMR (CDCl3) δ: 0.96 (6h, d,
J = 7.0 Hz, CH3), 1.03 (6H, d, J = 6.7 Hz, CH3), 1.14 (6H, s,
CH3), 2.02 (2H, qq, J = 6.7, 7.0 Hz, CH), 2.28 (2H, br, OH);
13C NMR (CDCl3) δ: 19.0, 19.7, 20.6, 33.2, 79.2. Anal.
calcd. for C10H22O2: C 68.92, H 12.72; found: C 68.96, H
12.59.
meso- and dl-3,4-diethyl-2,5-Dimethyl-3,4-hexanediol: Col-
orless oil. Anal. calcd. for C12H26O2: C 71.23, H 12.95;
found: C 71.51, H 12.55. Assignments were made by com-
paring the relative areas of methylene signals at δ 1.59 and δ
1.67, respectively. Separation of the pure isomers from crude
reaction mixture was achieved by the same method as the
case of 2,3,4,5-tetramehtyl-3,4-hexanediol.
meso- and dl-2,3-Dicyclohexyl-2,3-butanediol: Colorless
solid. Anal. calcd. for C16H30O2: C 75.54, H 11.89; found: C
75.78, H 11.52. Assignments were made by comparing the
relative heights of methyl signals at δ 1.14 and δ 1.15, re-
spectively. Separation of the pure isomers from crude reac-
tion mixture was achieved by the same method as the case of
2,3,4,5-tetramethyl-3,4-hexanediol.
(4RS,5RS)- and (2R,4RS,5SR)-4,5-diethyl-4,5-Diisopropyl-
2-phenyl-1,3-dioxolane: These two isomers were obtrained
from meso- and dl-2,5-dimethyl-3,4-diethyl-3,4-hexanediol:
(4RS,5RS)- and (2R,4RS,5SR)-4,5-Dicyclohexyl-4,5-dimethy-
2-phenyl-1,3-dioxolane: These two isomers were obtained
from meso- and dl-2,3-dicyclohexyl-2,3-butanediol:
(4RS,5RS)-Isomer (29% yield): Colorless oil; IR (neat) ν:
3062, 2978, 2877, 1458, 1381, 1219, 1095, 1026, 941, 764,
1
725, 702 cm–1; H NMR(CDCl3) δ: 0.84 (3H, dd, J = 7.3,
(4RS,5RS)-Isomer (29% yield): Colorless oil; IR (neat) ν:
3062, 2954, 2854, 1689, 1450, 1381, 1296, 1103, 1072,
1026, 926, 887, 764, 710 cm–1; 1H NMR(CDCl3) δ: 0.96–
1.33 (10H, m, CH2) 1.24 (3H, s, CH3), 1.27 (3H, s, CH3),
1.69–1.88 (10H, m, CH2), 1.99–2.02 (2H, m, CH), 5.82
(1H, s, CHPh), 7.30–7.37 (3H, m, Ph-H), 7.46–7.48 (2H, m,
Ph-H); 13C NMR(CDCl3) δ: 14.7, 17.6, 26.67, 26.74, 26.9,
27.1, 28.6, 28.8, 29.9, 30.3, 42.9, 44.0, 87.9, 88.0, 98.7,
126.6, 128.1, 128.6, 139.8; HRMS ([M + Na]+): calcd for
C23H34O2Na: 365.2457; found: 365.2440.
7.6 Hz, CH3) 0.99 (3H, d, J = 7.0 Hz, CH3), 1.02 (3H, d, J =
7.0 Hz, CH3), 1.06 (3H, dd, J = 7.3, 7.6 Hz, CH3), 1.06 (3H,
d, J = 7.0 Hz, CH3), 1.12 (3H, d, J = 7.0 Hz, CH3), 1.62
(1H, dq, J = 7.6, 14.6 Hz, CH2), 1.67 (1H, dq, J = 7.3,
14.6 Hz, CH2), 1.72 (1H, dq, J = 7.3, 14.6 Hz, CH2), 1.94
(1H, dq, J = 7.6, 14.6 Hz, CH2), 2.21 (1H, qq, J = 7.0,
7.0 Hz, CH), 2.29 (1H, qq, J = 7.0, 7.0 Hz, CH), 5.88 (1H, s,
PhCH), 7.28–7.36 (3H, m, Ph-H), 7.50–7.52 (2H, m, Ph-H);
13C NMR (CDCl3) δ: 9.7, 10.2, 19.31, 19.33, 20.3, 20.6,
22.8, 24.5, 31.0, 31.4, 90.0, 90.3, 98.7, 126.1, 127.91,
127.93, 140.6; HRMS ([M + Na]+): calcd for C19H31O2Na:
313.2144; found: 313.2093.
(2R,4RS,5SR)-Isomer88(19% yield): Colorless oil; IR (neat)
ν: 3008, 2924, 2854, 1682, 1612, 1450, 1373, 1242, 1141,
1
1095, 1025, 926, 849, 756 cm–1; H NMR(CDCl3) δ: 1.01–
(2R,4RS,5SR)-Isomer8 (11% yield): Colorless oil; IR (neat)
ν: 3062, 2962, 2870, 1458, 1381, 1219, 1095, 1018, 941,
1.34 (10H, m, CH2) 1.21 (6H, s, CH3), 1.61–1.96 (12H, m,
CH2+CH), 5.91 (1H, s, CHPh), 7.29–7.36 (3H, m, Ph-H),
7.47–7.49 (2H, m, Ph-H); 13C NMR (CDCl3) δ: 16.1, 25.9,
26.0, 26.1, 26.4, 26.5, 26.6, 26.8, 28.3, 28.7, 29.9, 31.5,
49.1, 51.8, 87.4, 99.0, 126.3, 128.0, 128.3, 139.8; HRMS
([M + Na]+): calcd for C23H34O2Na: 365.2457; found:
365.2388.
1
764, 725, 702 cm–1; H NMR (CDCl3) δ: 0.95 (6H, d, J =
7.0 Hz, CH3), 0.96 (6H, d, J = 6.7 Hz, CH3), 1.05 (6H, dd, J
= 7.3, 7.6 Hz, CH3), 1.71 (2H, dq, J = 7.3, 14.6 Hz, CH2),
1.87 (2H, dq, J = 7.6 Hz, CH2), 2.19 (2H, qq, J = 6.7,
7.0 Hz, CH), 5.89 (1H, s, CHPh), 7.29–7.36 (3H, m, Ph-H),
7.51–7.53 (2H, m, Ph-H); 13C NMR (CDCl3) δ: 10.2, 19.3,
20.2, 23.6, 31.5, 89.9, 98.8, 126.2, 127.9, 128.0, 140.2;
HRMS ([M + Na]+): calcd for C19H31O2Na: 313.2144;
found: 313.2199.
dl-2,3-Dicyclohexyl-2,3-butanediol: This isomer was obtained
from (4RS,5RS)-4,5-dicyclohexyl-4,5-dimethy-2-phenyl-1,3-
dioxolane in 99% yield. Colorless solid; mp 99–101°C; IR
(neat) ν: 3448, 2924, 2854, 1450, 1373, 1126, 1080, 1057,
dl-3,4-diethyl-2,5-Dimethyl-3,4-hexanediol: This isomer was
obtained from (4RS,5RS)-4,5-diisopropyl-4,5-diethy-2-phenyl-
1,3-dioxolane in 96% yield. Colorless oil; IR (KBr) ν: 3417,
2978, 2939, 1473, 1389, 1149, 964, 586, 555 cm–1; 1H NMR
(CDCl3) δ: 0.96 (6H, dd, J = 7.6, 7.6 Hz, CH3), 1.01 (6H, d,
J = 7.0 Hz, CH3), 1.03 (6H, d, J = 7.0 Hz, CH3), 1.67 (2H,
1
995, 926, 903, 602 cm–1; H NMR (CDCl3) δ: 1.02–1.31
(10H, m, CH2), 1.15 (6H, s, CH3), 1.65–1.83 (10H, m, CH2),
1.90–1.96 (2H, m, CH), 1.93 (2H, br, OH); 13C NMR
(CDCl3) δ: 19.6, 26.7, 27.0, 27.1, 28.0, 30.0, 44.5, 79.1;
HRMS ([M + Na]+): calcd for C16H30O2Na: 277.2143;
8 Only one Cs symmetric product was obtained. From meso diol, two isomers, i.e., (2R,4RS,5SR)-isomer and (2S,4RS,5SR)-isomer, are possi-
ble, but it was considered that the latter (all cis) would hardly be thermodynamically produced because of its steric hinderance.
© 2000 NRC Canada

Kagayama et al.
665
dq, J = 7.6, 14.7 Hz, CH2), 1.71 (2H, dq, J = 7.6, 14.7 Hz,
CH2), 2.08 (2H, qq, J = 7.0, 7.0 Hz, CH), 2.18 (2H, br, OH);
13C NMR (CDCl3) δ: 9.6, 18.9, 19.4, 27.1, 33.6, 80.7. Anal.
calcd. for C12H26O2: C 71.23, H 12.95; found: C 70.99, H
12.94.
1. (a) T. Mukaiyama, T. Sato, and J. Hanna. Chem. Lett. 1041
(1973); (b) S. Tyrlik and I. Wolochowicz. Bull. Soc. Chim. Fr.
2147 (1973); (c) J.E. McMurry and M.P. Fleming. J. Am.
Chem. Soc. 96, 4708 (1974).
2. (a) A. Fürstner and B. Bogdanovic. Angew. Chem. Int. Ed.
Engl. 35, 2442(1996); (b) T. Wirth. Angew. Chem. Int. Ed.
Engl. 35, 61 (1996); (c) A. Fürstner. Angew. Chem. Int. Ed.
Engl. 32, 164 (1993); (d) G.M. Robertson. In Comprehensive
organic synthesis. Vol. 3. Edited by B.M. Trost and I. Fleming.
Pergamon Press, Oxford, 1991, p. 563.
3. (a) Y. Handa and J. Inanaga. Tetrahedron Lett. 28, 5717
(1987); (b) A. Clerici, L. Clerici, and O. Porta. Tetrahedron
Lett. 37, 3035 (1996); (c) M.C. Barden and J. Schwartz. J.
Am. Chem. Soc. 118, 5484 (1996).
meso-3,4-diethyl-2,5-Dimethyl-3,4-hexanediol: This isomer
was obtained from (2R,4RS,5SR)-4,5-diisopropyl-4,5-diethyl-
2-phenyl-1,3-dioxolane in 94% yield. Colorless solid; mp
50–51°C; IR (KBr) ν: 3471, 2970, 2939, 1466, 1389, 1103,
1
957, 532 cm–1; H NMR (CDCl3) δ: 0.99 (6H, dd, J = 7.5,
7.3 Hz, CH3), 0.99 (6H, d, J = 7.0 Hz, CH3), 1.03 (6H, d, J
= 7.0 Hz, CH3), 1.59 (2H, dq, J = 7.3, 18.5 Hz, CH2), 1.71
(2H, dq, J = 7.5, 18.5 Hz, CH2), 2.07 (2H, qq, J = 7.0,
7.0 Hz, CH), 2.34 (2H, br, OH); 13C NMR (CDCl3) δ: 9.7,
18.9, 19.4, 26.4, 34.2, 80.9. Anal. calcd. for C12H26O2: C
71.23, H 12.95; found: C 71.04, H 12.78.
4. (a) J.L. Namy and H.B. Kagan. Tetrahedron Lett. 24, 765
(1983); (b) G.A. Molander. Chem. Rev. 92, 29 (1992); (c) N.
Taniguchi, N. Kaneta, and M. Uemura. J. Org. Chem. 61, 6088
(1996).
5. (a) J. Szymoniak, J. Besançon, and C. Moïse. Tetrahedron, 48,
3867 (1992); (b) J. Szymoniak, J. Besançon, and C. Moïse.
Tetrahedron, 50, 2841 (1994).
meso-, and dl-1,2-Diphenyl-1,2-ethanediol (18): Colorless
solid; H NMR (CDCl3) δ: 2.38 (2H, br, OH, meso), 3.04
(2H, br, OH, dl), 4.65 (2H, s, CH, dl), 4.79 (2H, s, CH,
meso), 7.07–7.30 (20H, m, Ph-H). Assignments were made
by comparing the relative heights of carbinol proton signals
at δ 4.67 and δ 4.79, respectively.
1
6. (a) R. Nomura, T. Matsuno, and T. Endo. J. Am. Chem. Soc.
118, 11666 (1996); (b) T.A. Lipski, M.A. Hilfiker, and S.G.
Nelson. J. Org. Chem. 62, 4566 (1997); (c) A. Gansäuer and
D. Bauer. J. Org. Chem. 63, 2070 (1998); (d) T. Hirao, M.
Asahara, Y. Muguruma, and A. Ogawa. J. Org. Chem. 63,
2812 (1998); (e) M. Bandini, P.G. Cozzi, S. Morganti, and A.
Umani-Ronchi. Tetrahedron Lett. 40, 1997 (1999).
7. N. Balu, S.K. Nayak, and A. Banerji. J. Am. Chem. Soc. 118,
5932 (1996).
meso-, and dl-1,6-Diphenyl-3,4-hexanediol (6a,b,d): Color-
1
less solid; H NMR (CDCl3) δ: 1.76–1.87 (8H, m, CH2),
2.65–2.90 (12H, m, CH2 + OH), 3.50 (2H, m, CH, dl), 3.65
(2H, m, CH, meso), 7.22–7.36 (20H, m, Ph-H). Assignments
were made by comparing the relative areas of carbinol pro-
ton signals at δ 3.50 and δ 3.65, respectively.
8. T. Mukaiyama, A. Kagayama, and I. Shiina. Chem. Lett. 1107
(1998).
9. (a) I. Shiina, H. Iwadare, H. Sakoh, M. Hasegawa, Y. Tani, and
T. Mukaiyama. Chem. Lett. 1 (1998); (b) T. Mukaiyama, I.
Shiina, H. Iwadare, M. Saitoh, T. Nishimura, N. Ohkawa, H.
Sakoh, K. Nishimura, Y. Tani, M. Hasegawa, K. Yamada, and
K. Saitoh. Chem. Eur. J. 5, 121 (1999).
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109 (1995); (b) J.J. Eisch, X. Shi, and J. Lasota. Z.
Naturforsch. B: Chem. Sci. 50, 342 (1995).
cis-1,2-Diphenyl-1,2-cyclohexanediol (15): Colorless solid;
1H NMR (CDCl3) δ: 2.02–1.91 (6H, m, CH2), 2.74–2.22
(2H, m, CH2), 2.94 (2H, br, OH), 7.12–7.03 (10H, m,Ph-H).
13C NMR (CDCl3) δ: 21.9, 35.9, 77.2, 126.7, 126.9, 127.1,
144.1.
12. (a) A. Ishida and T. Mukaiyama. Chem. Lett. 1127 (1976);
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Org. Chem. 61, 1101 (1996).
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27, 5763 (1986).
cis-, and trans-1,2-Dimethyl-1,2-cyclohexanediol: Assignments
were made by comparing the relative hights of methyl sig-
nals at δ 1.27 and δ 1.21, respectively. Identification of each
isomer was achieved as described below.
cis-1,2-Dimethyl-1,2-cyclohexanediol (21): Repeated thin layer
chromatography of the crude pinacol product gave pure cis-
isomer: Colorless solid; mp 48–50°C (lit. 51°C); H NMR
14. (a) R.J.H. Clark, J. Lewis, D.J. Machin, and R.S. Nyholm. J.
Chem. Soc. 379 (1963); (b) G.W.A. Fowles and T.E. Lester.
Chem. Commun. 47 (1967).
1
(CDCl3) δ: 1.21 (6H, s, CH3), 1.36–1.51 (4H, m, CH2),
1.57–1.64 (2H, m, CH2), 1.71–1.77 (2H, m, CH2), 2.20 (2H,
br, OH); 13C NMR (CDCl3) δ: 22.4, 23.6, 36.7, 74.0.
15. A. Fürstner and A. Hupperts. J. Am. Chem. Soc. 117, 4468
(1995).
16. J.E. McMurry and N.O. Siemers. Tetrahedron Lett. 34, 7891
(1993).
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(1968).
20. H. Birkhofer, H-D. Beckhaus, and C. Rüchardt. Chem. Ber.
126, 1023 (1993).
21. E.S. Huyser and L.G. Rose. J. Org. Chem. 37, 851 (1972).
trans-1,2-Dimethyl-1,2-cyclohexanediol (21): Separation of
the pure trans-isomer from crude reaction mixture was not
achieved. It was prepared according to the litarature. Color-
less solid, mp 90–92°C (lit. 93°C); 1H NMR (CDCl3) δ: 1.26
(6H, s, CH3), 1.43–1.50 (2H, m, CH2), 1.46 (2H, br, OH),
1.55–1.60 (4H, m, CH2), 1.71–1.75 (2H, m, CH2); 13C NMR
(CDCl3) δ: 22.0, 23.3, 36.4, 74.3.
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