2,6-Bis(2-alkylphenyl)-3,5-dimethylphenol as a new chiral phenol with C2-symmetry. Application to the asymmetric alkylation of aldehydes

Full text of DOI:10.1021/jo970747g

J . Org. Chem. 1997, 62, 5651-5656
5651
2,6-Bis(2-a lk ylp h en yl)-3,5-d im eth ylp h en ol
a s a New Ch ir a l P h en ol w ith C2-Sym m etr y.
Ap p lica tion to th e Asym m etr ic Alk yla tion
of Ald eh yd es
Susumu Saito, Taichi Kano, Keiko Hatanaka, and
Hisashi Yamamoto*
Graduate School of Engineering, Nagoya University,
CREST, J apan Science and Technology Corporation (J ST),
Furo-cho, Chikusa, Nagoya 464-01, J apan
Received April 28, 1997X
The desire to control the selectivity of carbon-carbon
bond-forming reactions in organic synthesis has led to
the design of various Lewis acid catalysts, which are
required to attach the proper ligands to an acidic metal
center. Various Lewis acid catalysts have been used for
this purpose in our laboratory,1 and each reagent has
characteristic features due to its unique steric factors.
In particular, aluminum tris(2,6-diphenylphenoxide) (AT-
PH)2 has been used as a typical designer Lewis acid
catalyst for regio-, chemo-, and stereoselective organic
reactions, and the structure of ATPH has been success-
fully extended to the chiral analogue aluminum tris((R)-
1-R-naphthyl-2-naphthoxide) ((R)-ATBN) for asymmetric
Claisen rearrangement.2c This result encouraged us to
explore the possibility of a new chiral phenol with C2-
symmetry. We report here the synthesis and optical
resolution of racemic 3,5-dimethyl-2,6-bis(2-methylphen-
yl)phenol (dl-1) and analogous 2,6-bis(2-isopropylphenyl)-
3,5-dimethylphenol (dl-2) for chiral aluminum reagents,
which were found to be effective for the enantioselective
alkylation of aldehydes (Figure 1).
Optically active 1 and 2 were synthesized as follows.
Regioselective dibromination of commercially available
3,5-dimethylphenol (3) with Br2 in the presence of 4 equiv
of t-BuNH2 followed by methylation of 4 with MeI and
K2CO3 in MeOH gave methyl ether 5 (68% yield from 3).
Subsequent Suzuki coupling3 of 5 with (2-methylphenyl)-
boronic acid [Pd(OAc)2, (o-tolyl)3P, Ba(OH)2, DME-H2O
(5:1); reflux for 4 h] gave racemic dl-6 and meso-6 in a
ratio of 1:1, which was then recrystallized from methanol
to give meso-6 in a yield of 45% as a colorless crystal.
The filtrate, which contained a 10:1 mixture of dl- and
meso-6, was purified by column chromatography on silica
gel to give dl-6 in a yield of 38%, which was demethylated
(BBr3, CH2Cl2), and the resulting dl-1 was converted into
camphorsulfonyl esters (R,R,S)-7 and (S,S,S)-7 (94%) by
sequential treatment with NaH and (+)-(S)-camphorsul-
fonyl chloride. The mixture of diastereomers (R,R,S)-7
and (S,S,S)-7 was separated by fractional recrystalliza-
F igu r e 1.
tion from ether to give enantiomerically pure (S,S,S)-7
(17%), which was subjected to desulfonylation (Na,
naphthalene, THF; -78 °C for 30 min) to furnish (S,S)-1
(>99% ee)4 in 68% yield (Scheme 1). (R,R)-1 can be
obtained readily by using (-)-camphorsulfonyl chloride.
The synthesis of (R,R)-2 and (S,S)-2 was initiated with
the introduction of sterically hindered 2-isopropylphenyl
groups to 5 by Suzuki coupling, which was carried out
using a sealed tube to give dl-8 in 46% yield.5 It should
be noted that no meso-8 could be detected. Sulfonylation
of dl-2 with n-BuLi and (+)-camphorsulfonyl chloride
after treatment of dl-8 with BBr3 gave a diastereomixture
of (R,R,S)-9 and (S,S,S)-9, which were separated by silica
gel column chromatography to furnish (R,R,S)-9 in 46%
yield together with a slightly impure (S,S,S)-9, which was
recrystallized from EtOAc to give enantiomerically pure
(S,S,S)-9 in 38% yield. Subsequent reduction of (R,R,S)-9
or (S,S,S)-9 with LiAlH4 in THF at reflux gave rise to
(R,R)-2 or (S,S)-2 in 82% yield. The absolute configura-
tion of (S,S)-2 was rigorously established by X-ray crystal
analysis of (S,S,S)-9,6 and those of (R,R)-2, (R,R)-1, and
(S,S)-1 could be assigned by correlating among the CD
spectra of these phenols.6
Scheme 2 shows an alternative approach to this type
of phenol. Tribromination of aniline 10 followed by
diazotization and iodination7 of 11 with KI gave tribro-
moiodobenzene 12 in an overall yield of 88%. The
successive generation of two different benzynes from 12
was promoted by treatment with 2 equiv of the Grignard
reagent,8 and transmetalation of the resulting (2,6-
diarylphenyl)magnesium species to BH3 was followed by
hydrolysis with H2O2-aqueous NaOH9 to give bromophe-
nol 13 in 42% yield in a dl:meso ratio of ca. 2:1.
Subsequent reduction with Bu3SnH proceeded smoothly
to give dl-2 and meso-2 (66:34) in 70% yield (overall yield
of dl-2 from 10 ) 17%).
(1) Methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD):
(a) Maruoka, K.; Itoh, T.; Sakurai, M.; Nonoshita, K.; Yamamoto, H.
J . Am. Chem. Soc. 1988, 110, 3588. (b) Maruoka, K.; Saito, S.;
Yamamoto, H. J . Am. Chem. Soc. 1992, 114, 1089. Methylaluminum
bis(4-bromo-2,6-di-tert-butylphenoxide) (MABR): (c) Maruoka, K.; Ooi,
T; Yamamoto, H. ibid. 1989, 111, 6431. (d) Maruoka, K.; Ooi, T.;
Yamamoto, H. ibid. 1990, 112, 9011. (e) Maruoka, K.; Sato, J .;
Yamamoto, H.; ibid. 1993, 113, 5449 (f) Maruoka, K.; Nonoshita, K.;
Banno, H.; Yamamoto, H. ibid. 1988, 110, 7922.
Neither the reaction of (R,R)-1 with Me3Al in CH2Cl2
or toluene upon reflux gave aluminum trisphenoxide 14,
but resulted in the formation of aluminum bisphenoxide
methylaluminum bis((R,R)-3,5-dimethyl-2,6-bis(2-meth-
(2) (a) Maruoka, K.; Imoto, H.; Saito, S.; Yamamoto, H. J . Am. Chem.
Soc. 1994, 116, 4131. (b) Maruoka, K.; Imoto, H.; Yamamoto, H. ibid.
1994, 116, 12115. ATPH for Claisen rearrangement: (c) Maruoka, K.;
Saito, S.; Yamamoto, H. ibid. 1995, 117, 1165. (d) Maruoka, K.; Ito,
M.; Yamamoto, H. ibid. 1995, 117, 9091. (e) Saito, S.; Ito, M.;
Yamamoto, H. ibid. 1997, 119, 611.
(3) (a) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh,
M.; Suzuki, A. J . Am. Chem. Soc. 1989, 111, 314. (b) Oh-e, T.; Miyaura,
N.; Suzuki, A. J . Org. Chem. 1993, 58, 2201.
(4) The optical purity was determined by chiral HPLC using a Daicel
column OD-H.
(5) Otherwise, the yield of dl-9 decreased significantly.
(6) See the Supporting Information.
(7) Hodgson, H. H.; Mahadevan, A. P. J . Chem. Soc. 1947, 173.
(8) Du, C.-J . F.; Hart, H.; Ng, K.-K. D. J . Org. Chem. 1986, 51, 3162.
(9) (a) Breuer, S. W.; Broster, F. A. J . Organomet. Chem. 1972, 35,
C5. (b) Brown, H. C.; Zweifel, G. Org. React. 1963, 13, 1.
S0022-3263(97)00747-0 CCC: $14.00 © 1997 American Chemical Society

5652 J . Org. Chem., Vol. 62, No. 16, 1997
Notes
Sch em e 1
Sch em e 2
Sch em e 3. P r ep a r a tion of Op tica lly Active
Alu m in u m Bisp h en oxid es
ylphenyl)phenoxide) [(R)-15], which was rigorously con-
firmed by 1H NMR measurement.10 A similar trend was
also observed with sterically more-hindered (R,R)-2 upon
reaction with Me3Al to produce methylaluminum bis-
((R,R)-2,6-bis(2-isopropylphenyl)-3,5-dimethylphenox-
ide) [(R)-16] as a sole product (Scheme 3).10 To determine
the potential of chiral phenols 1 and 2, asymmetric
alkylation of aldehydes11 was demonstrated by the com-
bined use of Grignard reagents and the optically active
aluminum reagents 15 and 16 (eq 1), and the results are
summarized in Table 1. This reaction had several
characteristic features: (1) Asymmetric induction of
aliphatic aldehydes was most highly promoted by using
3 equiv of 15, i.e., the % ee decreased with less 15 (<3
equiv) or with 3 equiv of 16. In contrast, reagent 16 was
more efficient for conjugated aldehydes such as benzal-
dehyde or cinnamaldehyde (17). Vinylation of 17 gave
allylic alcohols 24 and 25 with low to moderate selectivi-
ties. (2) The choice of the solvent for Grignard reagents
is crucial for obtaining higher % ee. For instance,
(11) (a) Weber, B.; Seebach, D. Tetrahedron, 1994, 50, 7473. (b)
Weber, B.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1992, 31, 84. (c)
Greeves, N.; Pease, J . E. Tetrahedron Lett. 1996, 37, 5821. (d) Chibale,
K.; Greeves, N.; Lyford, L.; Pease, J . E. Tetrahedron: Asymmetry 1993,
4, 2407. (e) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl.
1991, 30, 49. Dialkylzincs as alkylating agents: (f) Schmidt, B.;
Seebach, D. Angew. Chem., Int. Ed. Engl. 1991, 30, 1321. (g) Nowotny,
S.; Vettel, S.; Knochel, P. Tetrahedron Lett. 1994, 35, 4539. (h) Rozema,
M. J .; Sidduri, A.; Knochel, P. J . Org. Chem. 1992, 57, 1956. (i)
Chaloner, P. A.; Langadianou, E. Tetrahedron Lett. 1990, 31, 5185. (j)
Soai, K.; Niwa, S.; Hatanaka, T. J . Chem. Soc., Chem. Commun. 1990,
709. (k) Zhang, H.; Xue, F.; Mak, T. C. W.; Chan, K. S. J . Org. Chem.
1996, 61, 8002.
(10) The 1H NMR (300 MHz, toluene-d8) data of (R)-15: δ 7.20-
5.60 (m, 16H), 6.66 (s, 2H), 1.92 (s, 12H), 1.89 (s, 12H), -2.13 (s, 3H,
AlCH3). (R)-16: δ 7.60-6.70 (m, 16H), 6.57 (s, 2H), 2.95-2.41 (b, 4H),
2.05-1.62 (b, 12H), 1.14 (bd, 12H, J ) 6.1 Hz), 0.90-0.445 (b, 12H),
-2.54 (s, 3H, AlCH3).

Notes
Ta ble 1. Asym m etr ic Alk yla tion of Ald eh yd es w ith
J . Org. Chem., Vol. 62, No. 16, 1997 5653
Exp er im en ta l Section
Gr ign a r d Rea gen ts in th e P r esen ce of Op tica lly Active
15 or 16a
Gen er a l Meth od s. All experiments were carried out under
an atmosphere of dry argon. For thin-layer chromatography
(TLC) analysis throughout this work, Merck precoated TLC
plates (silica gel 60 GF254 0.25 mm) were used. The products
were purified by preparative column chromatography on silica
gel (E. Merck no. 9385). Optical rotations were measured using
a 3.5 mm × 0.5 dm Pyrex cell. Microanalyses were performed
at the Faculty of Agriculture, Nagoya University. Phenol 3,
aniline 10, and cinnamaldehyde (17) were obtained commer-
cially. Aniline derivative 1114 and chiral secondary alcohols 18,15
19,16 20,15 21,15 22,17 23,18 25,19 and 2617 are all known
compounds, and the spectral data, optical data, and analytical
data of these compounds which we obtained agreed with those
in the literature.
2,6-Dibr om o-3,5-d im eth ylp h en ol (4). To a solution of
t-BuNH2 (84.0 mL, 800 mmol) in dry toluene (800 mL) was added
Br2 (20.6 mL, 400 mmol) at -20 °C from a dripping funnel over
a period of 10 min. After the reaction mixture was cooled to
-78 °C, 3,5-dimethylphenol (24.4 g, 200 mmol) in CH2Cl2 (80
mL) was added over 5 min. The mixture was allowed to warm
to rt and then stirred for 20 h. The reaction was quenched with
1 M HCl, and the resulting mixture was extracted with Et2O.
The organic layer was dried over MgSO4 and concentrated. The
residue was recrystallized from Et2O-hexane at rt to yield the
product (33.9 g, yield 61%). 4: IR (KBr) 3457, 1294, 1239, 1194,
1058 cm-1 1H NMR (CDCl3, 300 MHz) δ 6.75 (s, 1H), 5.96 (s,
;
1H), 2.33 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ 149.0, 137.4,
123.9, 109.3, 22.8. Anal. Calcd for C8H8OBr2: C, 34.32; H, 2.88.
Found: C, 34.21; H, 2.88.
2,6-Dibr om o-3,5-d im eth yla n isole (5). A 200-mL, round-
bottomed flask was charged with 4 (3.23 g, 11.5 mmol), MeOH
(50 mL), and K2CO3 (4.77 g, 34.5 mmol). To this suspension
was added MeI (2.15 mL, 34.5 mmol), and the reaction mixture
was heated at reflux for 2 h, followed by the addition of MeI
(2.15 mL, 34.5 mmol). After stirring during reflux for 10 h, the
reaction mixture was cooled to rt, poured into aqueous NH4Cl,
and extracted with CH2Cl2. The organic layer was dried over
Na2SO4 and concentrated at reduced pressure using a rotary
evaporator. The residue was purified by column chromatogra-
phy on silica gel (Et2O/hexane ) 1/50 as the eluent) to give a
colorless solid (3.28 g, yield 97%). 5: IR (KBr) 1456, 1437, 1312,
1075 cm-1 1H NMR (CDCl3, 300 MHz) δ 6.93 (s, 1H), 3.86 (s,
;
3H), 2.33 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ 153.9, 138.0,
127.8, 117.5, 60.1, 22.9. Anal. Calcd for C9H10OBr2: C, 36.77;
H, 3.43. Found: C, 36.77; H, 3.43.
a
Unless otherwise specified, the reactions were carried out
using 15 or 16, an aldehyde, and a Grignard reagent in CH2Cl2 at
-78 °C for 30 min-2 h under the conditions as indicated in Table
m eso- a n d d l-3,5-Dim eth yl-2,6-bis(2-m eth ylp h en yl)a n i-
sole (m eso- a n d d l-6). A 300-mL, three-necked flask, equipped
with a magnetic stirring bar, reflux condenser, and a rubber
septum, was charged with tri-o-tolylphosphine (1.83 g, 6.0
mmol), Pd(OAc)2 (673 mg, 3.0 mmol), o-tolylboronic acid (12.2
g, 90.0 mmol), Ba(OH)2‚8H2O (28.4 g, 90.0 mmol), methyl ether
5 (8.70 g, 29.6 mmol), DME (120 mL), and H2O (24.0 mL). The
mixture was degassed at reduced pressure in vacuo at -20 °C
for ca. 20 min and then heated at reflux for 3 h. After being
cooled to rt, the mixture was poured into aqueous NH4Cl and
extracted with Et2O. The organic layer was dried over Na2SO4
and concentrated. The residue was purified by column chro-
matography on silica gel (Et2O/hexane ) 1/200 to 1/10 as the
eluent) to give a mixture of the diastereomers (8.80 g, yield 94%)
as colorless solids. Recrystallization of the isomeric phenols from
MeOH gave meso-6 (4.2 g, yield 45%) as a colorless crystal after
filtration and rinsing the cake with MeOH. The filtrate which
included a 1:10 (meso/dl) mixture of 6 was concentrated, and
the residue was purified by column chromatography on silica
gel (benzene/hexane ) 1/25 as the eluent) to give dl-6 (3.60 g,
b
1. Isolated yields. c Determined by chiral HPLC (column, OB-
d
H) analysis. Determined by comparison of reported optical
rotation. e GC yield. f Determined by HPLC using OD-H after
converting the products into phenyl carbamate (pyridine, phenyl
g
isocyanate, room temperature). Determined by chiral HPLC
(column, OD-H). Absolute configuration was not determined.
h
alkylation of 17 complexed with (R)-16 with a THF
solution of vinylmagnesium bromide gave alcohol 25 with
42% ee, whereas replacing THF with diglyme gave 25
with 6% ee. (3) The alkylation of aliphatic aldehydes and
(E)-2-hexenal with (S)-15 or (S)-16 proceeded favorably
from the si face of the carbonyl plane, while the re face
was preferred with benzaldehyde and 17. The origin of
this face reversibility is now under investigation in our
laboratory.12
The present result is one of the successful applications
of a Lewis acid-base complexation system to Grignard
reagents that is generally useful for asymmetric alkyla-
tion of aldehydes.
(14) (a) Kajigaeshi, S.; Kakinami, T.; Inoue, K.; Kondo, M.; Naka-
mura, H.; Fujikawa, M.; Okamoto, T. Bull. Chem. Soc. J pn. 1988, 61,
597. (b) J aeger, F.; Blanksma, J . Recl. Trav. Chim. Pays-Bas 1906,
25, 253.
(15) Sada, K.; Kondo, T.; Miyata, M. Tetrahedron: Asymmetry 1995,
6, 2655.
(16) Terashima, S.; Tanno, N.; Koga, K. Chem Lett. 1980, 981.
(17) Weber, B.; Seebach, D. Tetrahedron 1994, 50, 7473.
(18) Rozema, M. J .; Rajagopal, D.; Tucker, C. E.; Knochel, P. J .
Organomet. Chem. 1992, 438, 11.
(12) Optically active 15 and 16 were demonstrated to be more
effective than methylaluminum (R)-3,3′-bis(tris(4-methylphenyl)silyl)-
1,1′-bi-2-naphthoxide [(R)-27]:13 treatment of 17 with (R)-27 (1.2 equiv)
at -78 °C in toluene followed by the addition of an ether solution of
BuMgCl (2.0 equiv) gave, after 30 min, 23 in a yield of 89% with 5%
ee.
(13) (a) Maruoka, K.; Itoh, T.; Araki, Y.; Shirasaka, T.; Yamamoto,
H. Bull. Chem. Soc. J pn. 1988, 61, 2975. (b) Maruoka, K.; Concepcion,
A. B.; Yamamoto, H. Bull. Chem. Soc. J pn. 1992, 65, 3501.
(19) Burgess, K.; J ennings, L. D. J . Am. Chem. Soc. 1991, 113, 6129.

5654 J . Org. Chem., Vol. 62, No. 16, 1997
Notes
yield 38%) as a colorless solid. m eso-6: IR (KBr) 1454, 1393,
1308, 1287, 1271, 1073 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.29-
7.18 (m, 8H), 7.01 (s, 1H), 3.01 (s, 3H), 2.08 (s, 6H), 2.02 (s, 6H);
13C NMR (CDCl3, 75 MHz) δ 155.0, 137.6, 136.8, 136.4, 132.6,
129.8, 129.7, 127.0 (two overlapped signals), 125.3, 60.4, 20.0,
19.8. Anal. Calcd for C23H24O: C, 87.30; H, 7.64. Found: C,
87.29; H, 7.75. d l-6: IR (KBr) 1453, 1393, 1285, 1269, 1111,
1075 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.28-7.13 (m, 8H), 6.98
(s, 1H), 2.96 (s, 3H), 2.14 (s, 6H), 2.00 (s, 6H); 13C NMR (CDCl3,
75 MHz) δ 154.8, 137.6, 136.4, 136.3, 132.5, 130.0, 129.7, 127.0,
126.7, 125.4, 59.7, 19.9, 19.7. Anal. Calcd for C23H24O: C, 87.30;
H, 7.64. Found: C, 87.32; H, 7.71.
(s, 6H), 2.00 (s, 6H); 13C NMR (CDCl3, 75 MHz) δ 149.4, 137.4,
135.8, 130.4, 130.3, 127.9, 126.2, 125.0, 123.1, 19.8, 19.6. Anal.
Calcd for C22H22O: C, 87.38; H, 7.33. Found: C, 87.39; H, 7.61;
[R]25 ) +15.0° (c 1.00, CHCl3).
D
2-Isop r op yliod oben zen e. The reaction was carried out as
described in the literature.20 A 2-L, round-bottomed flask,
equipped with
a magnetic stirring bar, was charged with
2-isopropylaniline (84.9 mL, 600 mmol), H2O (250 mL), and 12
M HCl (250 mL, 3.0 mol). To the vigorously stirred mixture were
added ice (500 g) and NaNO2 (43.5 g, 630 mmol) in one portion.
After 10 min, to the resulting brown mixture was added a H2O
(250 mL) solution of KI (100.3 g, 604 mmol), and the mixture
was stirred at rt for 5 h, poured into H2O (250 mL), and extracted
with CH2Cl2. The organic layer was dried and concentrated, and
the residue was filtered through a short-path column of silica
gel (EtOAc/hexane ) 1/100 as the eluent). Fractions were
collected and concentrated, and the residual crude mixture was
distilled through a 40-cm Vigreux column to give 1-iodocumene
(70.9 g, yield 47%) as a wine-red liquid: 1H NMR (300 MHz,
CDCl3) δ 7.82 (d, 1H, J ) 7.9 Hz), 7.38-7.18 (m, 2H), 6.87 (t,
1H, J ) 7.6 Hz), 3.19 (heptet, 1H, J ) 6.8 Hz), 1.23 (d, 6H, J )
6.8 Hz).
(2-Isop r op ylp h en yl)bor on ic Acid . A 50-mL three-necked
flask, equipped with a magnetic stirring bar, a reflux condenser,
and a rubber septum, was charged with magnesium (729 mg,
30.0 mmol), which was activated as usual with heat under
reduced pressure, and furnished with an atmosphere of dry
argon. THF (25 mL) and 1,2-dibromoethane (100 µL) were
added to the flask, and to the resulting suspension was added
1-iodocumene (6.15 g, 25.0 mmol) dropwise with gentle heating.
When the reaction started, heating was discontinued, and the
reaction mixture was stirred as the remainder of the iodide was
added dropwise at a rate such that gentle reflux was maintained.
After the addition was complete, the mixture was stirred for an
additional 30-60 min and transferred via a steel cannula to a
THF (25 mL) solution of trimethylborate (5.88 mL, 50.0 mmol)
which was precooled to -78 °C under an argon atmosphere. The
entire mixture was then allowed to warm to rt and, after being
stirred for 1 h, was poured into 1 M HCl, extracted with Et2O,
dried, and concentrated. The residue was purified by column
chromatography on silica gel (EtOAc/hexane ) 1/3 as the eluent)
to give (2-isopropylphenyl)boronic acid (2.68 g, yield 65%) as a
colorless solid.
dl-3,5-Dim eth yl-2,6-bis(2-m eth ylph en yl)ph en ol (dl-1). To
a solution of dl-6 (1.00 g, 3.16 mmol) in CH2Cl2 (13.0 mL) was
added an excess of BBr3 dropwise at 0 °C under argon, and the
reaction mixture was stirred at 0 °C for 30 min. H2O was added
slowly and cautiously at the same temperature, followed by
dropwise addition of aqueous NaHCO3 over a few minutes,
during which time gas evolved vigorously. After the evolution
of gas was complete, the mixture was extracted with CH2Cl2.
The organic layer was dried and concentrated. The residue was
purified by column chromatography on silica gel (Et2O/hexane
) 1/9 as the eluent) to give a colorless solid (944 mg, yield 99%).
1H NMR, 13C NMR, and elemental analysis data of dl-1 were
consistent with those of (+)-(S,S)-1. Chiral HPLC analytical
data (column, OD-H) of dl-1: retention times tR ) 10.8 min for
(S,S)-1 and tR ) 13.8 min for (R,R)-1 using i-PrOH/hexane (1/
100) as the eluent at a flow rate of 0.5 mL/min.
(S,S)-3,5-Dim eth yl-2,6-bis(2-m eth ylp h en yl)p h en yl (+)-
(S)-Ca m p h or -10-su lfon a te [(S,S,S)-7]. To a suspension of
NaH (60% in oil; 322 mg, 13.4 mmol) in THF (100 mL) was added
dl-1 (4.06 g, 13.4 mmol) portionwise at 0 °C, and the reaction
mixture was stirred at rt under argon for 30 min. To the
resulting solution was added (+)-camphor-10-sulfonyl chloride
(3.36 g, 13.4 mmol) in one portion, and the mixture was stirred
for 2 h at rt. After the mixture was cooled to 0 °C, H2O was
added, and the resulting mixture was poured into aqueous NH4-
Cl, extracted with Et2O, dried, and concentrated. The residue
was purified by column chromatography on silica gel (Et2O/
hexane ) 1/4) to give (S,S,S)-7 and (R,R,S)-7 as colorless solids
(5.17 g, yield 75%). Recrystallization of the diastereomixture 7
from Et2O at rt with slow evaporation of the solvent gave one
diastereomer, (S,S,S)-7 (1.17 g, yield 17%, based on dl-1). HPLC
analytical data (column, Finepak SIL) of (R,R,S)-7 and (S,S,S)-
7: tR ) 19.8 min for (R,R,S)-7 and tR ) 20.7 min for (S,S,S)-7
using EtOAc/hexane (1/10) as the eluent at a flow rate of 1.0
mL/min. (S,S,S)-7: IR (KBr) 1750, 1456, 1395, 1368, 1250,
d l-2,6-Bis(2-isop r op ylp h en yl)-3,5-d im eth yla n isole (d l-8).
A 100-mL sealed tube equipped with a magnetic stirring bar
was charged with tri-o-tolylphosphine (365 mg, 1.20 mmol), Pd-
(OAc)2 (135 mg, 0.60 mmol), (2-isopropylphenyl)boronic acid (5.90
g, 36.0 mmol), K3PO4 (9.55 g, 45.0 mmol), 5 (4.4 g, 15.0 mmol),
DME (60.0 mL), and H2O (12.0 mL). The mixture was degassed
at reduced pressure in vacuo at -20 °C for ca. 20 min and heated
at reflux for 5 h. After being cooled to rt, the mixture was poured
into aqueous NH4Cl and was extracted with Et2O. The organic
layer was dried over Na2SO4 and concentrated. The residue was
purified by column chromatography on silica gel (EtOAc/hexane
) 1/300 to 1/50 as the eluent) to give a colorless solid (yield 46%).
1173, 1024 cm-1 1H NMR (CDCl3, 300 MHz) δ 7.27-7.19 (m,
;
8H), 7.16 (s, 1H), 2.60 (d, 1H, J ) 14.9 Hz), 2.27-1.71 (m, 5H),
2.16 (s, 6H), 2.05 (s, 6H), 1.67 (d, 1H, J ) 14.9 Hz), 1.42-1.19
(m, 2H), 0.86 (s, 3H), 0.58 (s. 3H); 13C NMR (CDCl3, 75 MHz) δ
213.3, 145.8, 137.0, 136.9, 136.2, 133.2, 130.8, 130.0 (two
overlapped signals), 127.9, 125.7, 57.6, 48.4, 47.6, 42.8, 42.3, 26.6,
25.0, 19.9, 19.7, 19.5 (two overlapped signals). Anal. Calcd for
d l-8: IR (KBr) 1605, 1306, 1283, 1084, 1030 cm-1 1H NMR
;
(CDCl3, 300 MHz) δ 7.39-7.10 (m, 8H), 6.96 (s, 1H), 3.00 (s,
3H), 2.79 (m, 2H), 2.02 (s, 6H), 1.17 (d, 6H, J ) 6.8 Hz), 1.15 (d,
6H, J ) 6.8 Hz); 13C NMR (CDCl3, 75 MHz) δ 155.6, 147.1, 136.6,
136.4, 131.9, 130.5, 127.5, 126.3, 125.3, 125.2, 60.3, 30.0, 24.3,
23.9, 20.3. Anal. Calcd for C27H32O: C, 87.05; H, 8.66. Found:
C, 87.04; H, 8.91. The procedure for demethylation of dl-6 was
followed except that dl-8 (4.30 g, 11.6 mmol) was used to give
dl-2,6-bis(2-isopropylphenyl)-3,5-dimethylphenol (dl-2) (3.80 g,
yield 91%) as a colorless solid. IR, 1H NMR, 13C NMR, and
elemental analysis data of dl-2 were consistent with those of
(-)-(R,R)-2.
(R,R)- a n d (S,S)-2,6-Bis(2-isop r op ylp h en yl)-3,5-d im eth -
ylph en yl (+)-(S)-Cam ph or -10-su lfon ate [(R,R,S)- an d (S,S,S)-
9]. To a solution of dl-phenol 2 (2.76 g, 7.70 mmol) in THF (50
mL) was added a 1.58 M hexane solution of n-BuLi (6.30 mL,
10.0 mmol) dropwise at 0 °C under an argon atmosphere. The
mixture was stirred at 0 °C for 30 min, followed by the addition
of (+)-(S)-camphor-10-sulfonyl chloride (3.86 g, 15.0 mmol) in
C
32H36O4S: C, 74.39; H, 7.02. Found: C, 74.40; H,7.20; [R]25
D
) +19.6° (c 1.00, CHCl3).
(+)-(S,S)-3,5-Dim et h yl-2,6-b is(2-m et h ylp h en yl)p h en ol
[(+)-(S,S)-1]. An oven-dried, 25-mL, Schlenk tube was charged
with naphthalene (497 mg, 3.88 mmol) and THF (5 mL). To
this mixture was added small pieces of sodium (89 mg, 3.88
mmol) portionwise at rt under a gentle stream of argon, and
the resulting dark purple suspension was stirred at rt for 2 h.
After the mixture was cooled to -78 °C, optically active (S,S,S)-7
(100 mg, 0.19 mmol) in THF (1 mL) was added, and the mixture
was maintained at -78 °C with stirring for an additional 20
min. The reaction was quenched by dropwise addition of MeOH
at -78 °C until the dark color disappeared. The mixture was
poured into 1 M HCl, extracted with Et2O, dried over Na2SO4,
and concentrated. The crude product was purified by column
chromatography on silica gel (CH2Cl2/hexane ) 1/2 as the eluent)
to give colorless solids (40 mg, yield 68%). (+)-(S,S)-1: IR (KBr)
3497, 1449, 1402, 1291, 1233, 1152, 1049 cm-1; 1H NMR (CDCl3,
300 MHz) δ 7.30-7.16 (m, 8H), 6.82 (s, 1H), 4.42 (s, 1H), 2.12
(20) Bolton, R.; Sandall, J . P. B. J . Chem. Soc., Perkin Trans. 2 1977,
278.

Notes
J . Org. Chem., Vol. 62, No. 16, 1997 5655
one portion, and the resulting mixture was stirred at rt for 3 h.
The reaction mixture was poured into aqueous NH4Cl and
extracted with Et2O. The organic layer was dried and concen-
trated. The residue was purified by column chromatography on
silica gel (EtOAc/hexane ) 1/50 as the eluent) to give pure
(R,R,S)-9 (1.85 g, yield 42%) and a ca. 1:20 diastereomixture of
(R,R,S)-9 and (S,S,S)-9 (yield 46%), which was recrystallized
from EtOAc at rt to give pure (S,S,S)-9 (1.68 g, yield 38%).
(R,R,S)-9: IR (KBr) 1748, 1474, 1397, 1368, 1250, 1177, 1026
Red u ction of d l-13 a n d m eso-13 w ith Bu 3Sn H. A 2:1
mixture of dl-13 and meso-13 (39.5 mg, 0.09 mmol) in Bu3SnH
(500 µL) was heated at 140 °C for 3 h and purified by column
chromatography on silica gel (hexane only to EtOAc/hexane )
1/30 as the eluent) to give dl-2 and meso-2 (22.6 mg, 0.063 mmol)
in 70% yield in a ratio of 2:1. m eso-2: IR (KBr) 3584, 1443,
1291, 1037 cm-1 1H NMR (CDCl3, 300 MHz) δ 7.45-7.15 (m,
;
8H), 6.83 (s, 1H), 4.41 (s, 1H), 2.75 (m, 2H), 2.02 (s, 6H), 1.16
(d, 6H, J ) 6.9 Hz), 1.10 (d, 6H, J ) 6.9 Hz); 13C NMR (CDCl3,
75 MHz) δ 150.1, 148.1, 136.1, 134.2, 130.3, 128.4, 126.2, 125.8,
124.8, 123.0, 30.1, 24.2, 23.8, 20.1. Anal. Calcd for C26H30O:
C, 87.10; H, 8.43. Found: C, 87.02; H, 8.59.
cm-1 1H NMR (CDCl3, 300 MHz) δ 7.44-7.15 (m, 9H), 2.80-
;
2.70 (m, 3H), 2.26-1.69 (m, 5H), 2.07 (s, 6H), 1.43 (d, 1H, J )
14.9 Hz), 1.37-1.12 (m, 2H), 1.26 (d, 6H, J ) 6.8 Hz), 1.16 (d,
6H, J ) 6.8 Hz), 0.88 (s, 3H), 0.60 (s, 3H); 13C NMR (CDCl3, 75
MHz) δ 213.4, 147.7, 146.1, 137.3, 134.7, 133.2, 130.8, 129.8,
128.3, 125.8, 125.4, 57.8, 48.6, 47.4, 42.9, 42.2, 30.2, 26.6, 25.0,
24.5, 23.8, 20.4, 19.6, 19.5. Anal. Calcd for C36H44O4S: C, 75.49;
P r ep a r a tion of (R)-15. To a toluene (4.0 mL) solution of
phenol (R,R)-1 (258 mg, 0.72 mmol; 2 equiv) was added a 1.0 M
hexane solution of Me3Al (0.36 mL, 0.36 mmol; 1 equiv) dropwise
at 50 °C under argon with rigorous exclusion of air and moisture,
and the mixture was stirred for 1 h. When CH2Cl2 was used as
a solvent, the preparation was conducted at reflux for 1 h. (R)-
16 could be prepared similarly. Both the solutions of the
reagents were used for the following alkylation experiments
without further purification.
H, 7.74. Found: C, 75.50; H, 8.07. [R]25 ) -13.0° (c 1.00,
D
CHCl3). (S,S,S)-9: IR (KBr) 1748, 1474, 1395, 1372, 1250, 1173,
1026 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.42-7.15 (m, 9H), 2.74
(m, 2H), 2.24 (d, 1H, J ) 14.8 Hz), 2.16-1.13 (m, 7H), 2.08 (s,
6H), 1.88 (d, 1H, J ) 14.8 Hz), 1.25 (d, 6H, J ) 6.8 Hz), 1.18 (d,
6H, J ) 6.8 Hz), 0.80 (s, 3H), 0.58 (s, 3H); 13C NMR (CDCl3, 75
MHz) δ 213.0, 147.6, 146.5, 137.3, 134.7, 133.1, 131.1, 130.0,
128.3, 125.8, 125.5, 57.6, 48.9, 47.7, 42.9, 42.3, 30.1, 26.7, 25.2,
24.4, 24.1, 20.4, 19.6, 19.5. Anal. Calcd for C36H44O4S: C, 75.49;
Gen er a l P r oced u r e for En a n tioselective Alk yla tion of
Ald eh yd es. To a CH2Cl2 (4.0 mL) solution of (R)-16 (1.2 equiv)
was added cinnamaldehyde (17) (38 µL, 0.3 mmol) at -78 °C
under argon, and the mixture was stirred for ca. 10 min. To this
solution was added a 1.86 M Et2O solution of BuMgCl (0.32 mL,
0.6 mmol) dropwise at -78 °C, and the mixture was stirred for
0.5-1 h, quenched with 1 M HCl, and extracted with EtOAc.
The organic layer was dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by column chro-
matography on silica gel (EtOAc/hexane ) 1/20 to Et2O/hexane
) 1/3 as the eluent) to give 1-phenyl-1-hepten-3-ol (23) (49 mg,
yield 86%) as a colorless liquid.
H, 7.74. Found: C, 75.48; H, 8.01. [R]25 ) +51.2° (c 1.00,
D
CHCl3).
(-)-(R,R)-2,6-Bis(2-isop r op ylp h en yl)-3,5-d im et h ylp h e-
n ol [(-)-(R,R)-2]. To a suspension of LiAlH4 (53 mg, 1.40 mmol)
in THF (17.5 mL) was added (R,R,S)-9 (100 mg, 0.18 mmol)
portionwise at rt. The mixture was immersed in an oil bath at
50 °C and maintained at this temperature for 9 h. After the
reaction mixture was cooled to 0 °C, H2O was added dropwise
until no gas evolution was observed. The mixture was poured
into 1 M HCl, extracted with Et2O, dried over Na2SO4, and
concentrated. The residual crude product was purified by
column chromatography on silica gel (EtOAc/hexane ) 1/60 as
the eluent) to give a colorless solid (52 mg, yield 82%). (-)-
(R,R)-2: IR (KBr) 3530, 1445, 1306, 1242, 1154 cm-1; 1H NMR
(CDCl3, 300 MHz) δ 7.45-7.10 (m, 8H), 6.81 (s, 1H), 4.38 (s,
1H), 2.76 (m, 2H, J ) 6.9 Hz), 2.01 (s, 6H), 1.16 (d, 6H, J ) 6.9
Hz), 1.11 (d, 6H, J ) 6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ 150.2,
148.2, 136.1, 134.5, 130.4, 128.4, 126.2, 125.8, 124.9, 122.9, 30.2,
24.2, 23.7, 20.1. Anal. Calcd for C26H30O: C, 87.10; H, 8.43.
Ch ir a l HP LC a n a lysis of 21-25. 21 (column, OB-H):
retention times tR ) 13.0 min for (R)-21 and tR ) 17.4 min for
(S)-21 using i-PrOH/hexane (1/9) as the eluent at a flow rate of
0.5 mL/min. 22 (column: OB-H): retention times tR ) 14.9 min
for (S)-22 and tR ) 18.0 min for (R)-22 using i-PrOH/hexane (1/
20) as the eluent at a flow rate of 0.5 mL/min. 23 (column, OB-
H): retention times tR ) 15.1 min for (R)-23 and tR ) 18.2 min
for (S)-23 using i-PrOH/hexane (1/9) as eluent at a flow rate of
0.5 mL/min. 24 (column, OD-H); retention times tR ) 8.95 min
and tR ) 12.61 min (the later peak for the major enantiomer
when (R)-16 was used) using i-PrOH/hexane (1/9) as the eluent
at a flow rate of 1.0 mL/min. 25 (column, OD-H); retention times
tR ) 10.6 min for (R)-25 and tR ) 15.4 min for (S)-25 using
i-PrOH/hexane (1/9) as the eluent at a flow rate of 1.0 mL/min.
Found: C, 87.10; H, 8.78. [R]25 ) -58.1° (c 1.00, CHCl3).
D
2,4,6-Tr ibr om oiod oben zen e (12). 12 was prepared as
described in the literature.7 12: IR (KBr) 1375, 1337, 963 cm-1
;
1H NMR (CDCl3, 300 MHz) δ 2.79 (s, 6H); 13C NMR (CDCl3, 75
MHz) δ 138.5, 130.4, 127.9, 110.8, 29.1. Anal. Calcd for C8H6-
Br3I: C, 20.50; H, 1.29. Found: C, 20.60; H, 1.28.
4-Meth yl-1-p h en yl-1,4-p en ten -3-ol (24): IR (neat) 3083,
3029, 1449, 1094 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.40-7.21
(m, 5H), 6.63 (d, 1H, J ) 15.9 Hz), 6.20 (dd, 1H, J ) 15.9, 6.6
Hz), 5.10 (s, 1H), 4.91 (s, 1H), 4.71 (d, 1H, J ) 6.6 Hz), 1.90 (bs,
1H), 1.77 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 146.2, 136.5,
131.1, 130.2, 128.5, 127.8, 126.4, 111.2, 76.3, 18.3. Anal. Calcd
d l- a n d m eso-4-Br om o-2,6-b is(2-isop r op ylp h en yl)-3,5-
d im eth ylp h en ol (d l- a n d m eso-13).8,9 To a THF solution of
(2-isopropylphenyl)magnesium iodide (3.5 mL, 1.5 mmol) was
added 12 (236 mg, 0.5 mmol) in THF (7.0 mL) dropwise over 1h
at rt under argon, and the mixture was stirred at rt for 3.5 h.
The mixture was cooled to -78 °C, a 1.0 M THF solution of BH3
(2.5 mL, 2.5 mmol) was added, and the resulting mixture was
stirred at rt for 3 h. To this mixture were added sequentially a
3.0 M aqueous solution of NaOH (2.2 mL, 6.6 mmol) and 30 wt
% aqueous H2O2 (2.2 mL, 20 mmol) at the same temperature.
After 4 days of stirring, 4 g of K2CO3 was added. The entire
mixture was then extracted twice with THF. The organic layer
was dried, concentrated, and purified by column chromatography
on silica gel (hexane only to EtOAc/hexane ) 1/20 as the eluent)
to give a mixture of dl- and meso-13 (yield 28% and 14%,
respectively). d l-13: IR (KBr) 3530, 1441, 1235, 1084 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 7.45-7.07 (m, 8H), 4.38 (s, 1H), 2.73
(m, 2H), 2.15 (s, 6H), 1.15 (d, 6H, J ) 6.9 Hz), 1.10 (d, 6H, J )
6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ 149.3, 148.0, 136.2, 134.5,
130.2, 128.7, 126.3, 126.0 (two overlapped signals), 119.4, 30.3,
24.1, 23.6, 21.9. Anal. Calcd for C26H29OBr: C, 71.39; H, 6.68.
Found: C, 71.34; H, 6.59. m eso-13: IR (KBr) 3528, 1445, 1283,
1232, 1157, 1057 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.45-7.10
(m, 8H), 4.40 (s, 1H), 2.70 (m, 2H), 2.16 (s, 6H), 1.15 (d, 6H, J )
6.9 Hz), 1.08 (d, 6H, J ) 6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ
149.3, 148.0, 136.2, 134.3, 130.2, 128.7, 126.3, 126.0, 125.5, 119.5,
30.2, 24.1, 23.7, 21.9. Anal. Calcd for C26H29OBr: C, 71.39; H,
6.68. Found: C, 71.33; H, 6.64.
for C12H14O: C, 82.72; H, 8.10. Found: C, 82.40; H, 8.49. [R]25
) -11.0° (c 0.94, CHCl3) for an 80% ee of 24.
D
P r ep a r a tion of P h en yl Ca r ba m a tes fr om Alcoh ols for
HP LC An a lysis. To a pyridine solution of an alcohol was added
phenyl isocyanate at rt, and the mixture was stirred for 0.5 h.
Pyridine was removed under reduced pressure (1-3 mmHg). The
residue was purified by column chromatography on silica gel.
HP LC An a lytica l Da ta of Som e Ca r ba m a tes Usin g th e
Colu m n OD-H. P h en yl ca r ba m a te fr om 18: retention times
tR ) 16.5 min for (S)-18 and tR ) 39.8 min for (R)-18 using
i-PrOH/hexane (1/9) as the eluent at a flow rate of 0.5 mL/min.
P h en yl ca r ba m a te fr om 19: retention times tR ) 6.87 min for
(S)-19 and tR ) 14.3 min for (E)-19 using i-PrOH/hexane (1/9)
as the eluent at a flow rate of 1.0 mL/min. P h en yl ca r ba m a te
fr om 20: retention times tR ) 13.7 min for (S)-20 and tR ) 21.7
min for (R)-20 using i-PrOH/hexane (1/20) as the eluent at a
flow rate of 1.0 mL/min. P h en yl ca r ba m a te fr om 26: retention
times tR ) 5.97 min for (R)-26 and tR ) 7.65 min for (S)-26 using
i-PrOH/hexane (1/9) as the eluent at a flow rate of 0.5 mL/min.
Ack n ow led gm en t. We gratefully acknowledge fi-
nancial support from the Ministry of Education, Science,
and Culture of J apan. We also appreciate the assistance

5656 J . Org. Chem., Vol. 62, No. 16, 1997
Additions and Corrections
electronically) and the X-ray crystal data of (S,S,S)-9 (12
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from ACS; see any current
masthead page for ordering information and instructions on
accessing the color image.
of A. Nakao (MAC Science Co., Ltd.) for the X-ray crystal
analysis of sulfonate (S,S,S)-9 and A. Takakuwa (J AS-
CO., Ltd.) for the CD spectral analysis of (R,R)- and
(S,S)-1 and 2.
Su p p or tin g In for m a tion Ava ila ble: CD spectra of (S,S)-
and (R,R)-1 and 2 (black and white version is available on
microfiche and in microfilm version; color spectra are available
J O970747G
Additions and Corrections
Vol. 61, 1996
Page 2554. The preparation of 22 and 23 should read
as follows: The residue was purified by flash column
chromatography to give compound 22 (96 mg, 12% from
9) and 23 (248 mg, 30% from 9).
Na ok i Asa o, Tom ok o Su d o, a n d Yosh in or i Ya m a m oto*.
Lewis Acid-Catalyzed trans-Hydrosilylation of Alkynes.
Page 7654, Table 1. The structures of 1d and 2d
should read as follows: R1 ) H, R2 ) Me3Si.
J O974011V
J O974013F
S0022-3263(97)04011-5
S0022-3263(97)04013-9
Vol. 62, 1997
J oh n D. Tova r , Nor ber t J u x, Th iba u t J a r r osson ,
Sa eed I. Kh a n , a n d Yves Ru bin *. Synthesis and X-ray
Characterization of an Octaalkynyldibenzooctadehydro[12]-an-
nulene.
P a u l S. En gel,* Sh u -Lin He, J . T. Ba n k s, K. U. In gold ,
a n d J . Lu sztyk . Clocking Tertiary Cyclopropylcarbinyl Radical
Rearrangements.
Page 3432, column 2. During the production of the
journal, text was deleted from the paragraph beginning
at the bottom of the page (the electronic file is correct).
The entire paragraph is given below:
Page 1210. The units given for k1 in the abstract
should be s-1, not M-1 s-1. The authors at Rice Univer-
sity gratefully acknowledge the National Science Foun-
dation and the Robert A. Welch Foundation for support
of this research.
Interestingly, bis(trimethyl)silyl)hexatriyne (5f)10 did
not add to dienones 1a ,b across its central, least sterically
hindered CtC bond11 to give the desired C2v-symmetric
HEBs, but rather at one of the two peripheral triple
bonds to give 6f and 6j. This can be understood as a
result of the large steric repulsion created between the
TMS and t-Bu/TIPS groups at the transition state (T.S.,
Figure 2);12 an unsymmetrical approach is more favor-
able. Since the more extended diynyl system of the green
cyclopentadienone 1c should not display this steric bias,
its reaction with hexatriyne 5f was attempted. Unfor-
tunately, the expected symmetrical adduct 6k was not
observed among a complex mixture of highly colored
compounds.
J O974012N
S0022-3263(97)04012-7
Hu i-Yin Li,* In d a w a ti DeLu cca , Sp en cer Dr u m m on d ,
a n d Geor ge A. Br osw ell. An Unusual Trifluoromethyl Elimi-
nation Reaction From the 4,4-Bis(trifluoromethyl)-5-hydroxy-
imidazoline Ring System.
Page 2250, column 2. The following structures should
be inserted before the Results and Discussions section.
J O9740148
S0022-3263(97)04014-0