Preparation of Enantiopure 2,2,5,5-Tetramethyl-3,4-hexanediol and Its Use in Catalytic Enantioselective Oxidation of Sulfides to Sulfoxides

Full text of DOI:10.1021/jo971004y

8
560
J . Org. Chem. 1997, 62, 8560-8564
5
6,7
P r ep a r a tion of En a n tiop u r e
of diols, the use of diastereomer phosphate esters and
related compounds8 was found to be highly effective.
Taking account of these previously established methods,
we devised a new method for the resolution of the dl-1
via the formation of the corresponding phosphine-borane
bearing an l-menthyloxy group. Racemic diol 1 was
converted by successive reactions with n-BuLi, dichloro-
,9
2
,2,5,5-Tetr a m eth yl-3,4-h exa n ed iol a n d Its
Use in Ca ta lytic En a n tioselective
Oxid a tion of Su lfid es to Su lfoxid es
Yoshinori Yamanoi and Tsuneo Imamoto*
(
l-menthyloxy)phosphine, and BH
omer mixture of 2-boranato-2-(1′R,2′S,5′R)-((2′-isopropyl-
′-methylcyclohexyl)oxy)-4,5-di-tert-butyl-1,3,2-dioxa-
3
-THF to a diastere-
Department of Chemistry, Faculty of Science, Chiba
University, Yayoi-cho, Inage-ku, Chiba 263, J apan
5
phospholane. Separation of two diastereomers was
achieved by fractional recrystallization from methanol.
Reaction of one diastereomer 2 with excess MeLi (5 equiv)
in toluene provided enantiopure (+)-diol 1 in 95%. In a
similar manner, enantiopure (-)-diol 1 was also prepared
in 90% from the other diastereomer 3.
Received J une 4, 1997
In tr od u ction
Optically active 1,2-diols and related substrates play
significant roles as chiral auxiliaries in the synthesis of
natural products and biologically active compounds.
2
Recently, chiral catalysts derived from certain C -sym-
metric 1,2-diol ligands have been found to show high
enantioselectivities in some asymmetric reactions.2 These
successful results led us to design a more effective chiral
ligand. We considered that 2,2,5,5-tetramethyl-3,4-hex-
anediol (1) might be an efficient chiral ligand because it
has a remarkable steric contrast between the bulky tert-
butyl group and the hydrogen atom. This compound,
however, has not been synthesized in optically pure
The absolute configuration of diol (+)-1 was determined
on the basis of X-ray structural analysis of diastereomer
1
2
. The ORTEP drawing of compound 2 is shown in
Figure 1. The configuration of this diol was assigned to
be (S,S) based on the relative stereochemistry to the
known configuration of the l-menthyloxy group. Accord-
ingly, (-)-diol 1 should possess (R,R) configuration.
Ca t a lyt ic Asym m et r ic Oxid a t ion of Su lfid es.
Asymmetric oxidation of sulfides has recently become a
useful means of the preparation of optically active
sulfoxides.1
0,11
The most straightforward procedures
3
form, and, furthermore, its utility in organic synthesis
involve the use of commercially available enantiopure
has not yet been examined. In this paper we report a
new preparation of enantiopure diol 1 and its utilization
as a chiral ligand in titanium(IV)-catalyzed enantiose-
lective oxidation of sulfides.
reagents as chiral auxiliaries. For example, the employ-
ment of Ti(IV)-diethyl tartrate1
2a-h
or Ti(IV)-bi-
naphthol1
2i-k
systems has resulted in high levels of
enantioselectivity. However, the possibility of different
diols has been scarcely explored.1
2l,m
To test the catalytic
efficiency of chiral diol 1, we examined asymmetric
oxidation of sulfides using a Ti(IV)-diol 1 complex as a
catalyst.
The asymmetric oxidation of methyl p-tolyl sulfide was
carried out as a model reaction. The results are sum-
marized in Table 1. The chiral titanium complex was
i
Resu lts a n d Discu ssion
prepared in situ from Ti(O Pr)
4
and (3S,4S)-2,2,5,5-
tetramethyl-3,4-hexanediol. In the presence of this chiral
Op tica l Resolu tion of 2,2,5,5-Tetr a m eth yl-3,4-h ex-
a n ed iol. Our synthetic route to enantiopure 2,2,5,5-
tetramethyl-3,4-hexanediol (1) is shown in Scheme 1.
Initially, the racemic 1,2-diol 1 was prepared by reductive
coupling of pivalaldehyde. After screening various cou-
pling reagents, we found that a low-valent titanium
titanium catalyst, methyl p-tolyl sulfide reacted with tert-
(5) (a) Newman, P. Optical Resolution Procedures for Chemical
Compounds. Alcohols, Phenols, Thiols, Aldehydes and Ketones; Optical
Resolution Information Center: New York, 1984; Vol. 3. (b) J acques,
J .; Collet, A.; Wilen, S. H. Enantiomers, Racemates, and Resolution;
J ohn Wiley and Sons: New York, 1981.
(6) (a) Brunel, J . M.; Buono, G. J . Org. Chem. 1993, 58, 7313. (b)
Brunel, J . M.; Faure, B. Tetrahedron: Asymmetry 1995, 6, 2353. (c)
Imamoto, T.; Yoshizawa, T.; Hirose, K.; Wada, Y.; Masuda, H.;
Yamaguchi, K.; Seki, H. Heteroatom. Chem. 1995, 6, 99.
(7) (a) J acques, J .; Fouquey, C. Org. Synth. 1988, 67, 1. (b)
Truesdale, L. K. Org. Synth. 1988, 67, 13.
4
reagent gave the best result. Pivalaldehyde was treated
with the titanium reagent (prepared in situ from TiCl
4
4
b,c
and Mg powder ) to provide the 1,2-diol 1 as a 98/2
mixture of dl- and meso-isomers in 42% yield. Recrys-
tallization of the mixture from hexane gave a pure dl-
isomer as colorless needles.
(8) Gong, B.; Chen, W.; Hu, B. J . Org. Chem. 1991, 56, 423.
(9) (a) Fabbri, D.; Delogu, G.; Lucchi, O. D. J . Org. Chem. 1993, 58,
748. (b) Delogu, G.; Fabbri, D. Tetrahedron: Asymmetry 1997, 8, 759.
1
We next examined the optical resolution of racemic
compound 1. Among many methods for optical resolution
(
10) For some reviews on the synthesis and application of chiral
sulfoxide, see: (a) Solladie, G. Synthesis 1981, 185. (b) Andersen, K.
K. in The Chemistry of Sulfones and Sulfoxides; Patai, S., Rappoport,
Z., Stirling, C. J . M., Eds.; Wiley and Sons, Ltd.: Chichester, England,
1988; Chapter 3, pp 55-94. (c) Posner, G. H. Ibid. Chapter 16, pp
823-849.
(11) (a) Kagan, H. B. Asymmetric Oxidation of Sulfides. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993, pp 203-
226. References cited therein. (b) Noda, K.; Hosoya, N.; Yanai, K.;
Irie, N.; Katsuki, T. Tetrahedron Lett. 1994, 35, 1887. (c) Noda, K.;
Hosoya, N.; Irie, R.; Yamashita, Y.; Katsuki, T. Tetrahedron 1994, 50,
9609. (d) Kokubo, C; Katsuki, T. Tetrahedron 1996, 52, 13895. (e)
Imagawa, K.; Nagata, T.; Yamada, T.; Mukaiyama, T. Chem. Lett.
1995, 335. (f) Nagata, T.; Imagawa, K.; Yamada, T.; Mukaiyama, T.
Bull. Chem. Soc. J pn. 1995, 68, 3241. (g) Furia, F. D.; Licini, G.;
Modena, G.; Motterle, R.; Nugent, W. A. J . Org. Chem. 1996, 61, 5175.
(
1) Reviews; (a) Alexakis, A.; Mangnency, P. Tetrahedron: Asym-
metry 1990, 1, 477. (b) Whitesell, J . K. Chem. Rev. 1989, 89, 1581.
2) (a) Prasad, K. R. K.; J oshi, N. N. Tetrahedron: Asymmetry 1996,
, 1957. (b) Devine, P. N.; Oh, T.; J . Org. Chem. 1992, 57, 396.
3) In the past, the optically active diol 1 was prepared by the
(
7
(
Sharpless osmium-catalyzed asymmetric dihydroxylation of (E)-2,2,5,5-
tetramethyl-3-hexene (86%, 62% ee). Hentges, S. G.; Sharpless, K. B.
J . Am. Chem. Soc. 1980, 102, 4263.
(
4) (a) Mukaiyama, T.; Sato, T.; Hanna, J . Chem. Lett. 1973, 1041.
(
b) Corey, E. J .; Danheiser, R. L.; Chandrasekaran, S. J . Org. Chem.
1
2
976, 41, 260. (c) Rao, S. A.; Periasamy, M. Tetrahedron Lett. 1988,
9, 1583.
S0022-3263(97)01004-9 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 24, 1997 8561
Sch em e 1
both optical and chemical yields (entries 4 and 5). It was
found that nonpolar aromatic solvents were appropriate
for this asymmetric oxidation. In toluene, methyl p-tolyl
sulfoxide was obtained in the highest optical yield (95%
ee), although a considerable amount of sulfone was also
observed. In contrast, the reaction in CH
Cl was slug-
2 2
gish, and the enantiomeric excess of the product was only
moderate. Although the precise structure of the catalyst
has not yet been clarified, it was found that 1:2 ratio of
i
Ti(O Pr)
4
and diol 1 gave the maximum enantiomeric
excess. The reaction temperature also affected both
chemical and optical yields. It was found that optimum
temperature for this reaction was around -20 °C.
To clarify the generality and scope of this asymmetric
reaction, enantioselective oxidations of several prochiral
sulfides were examined. The results are shown in Table
2
. Although this catalyst has proved to be ineffective in
F igu r e 1. ORTEP drawing of compound 2.
the case of dialkyl sulfides (entries 9 and 10), aryl alkyl
sulfoxides with various substituents on the aromatic ring
were obtained in good to high enantioselectivities (entries
butyl hydroperoxide at -20 °C to afford the correspond-
ing sulfoxide in 70% yield, but the enantiomeric excess
was shown to be 10% (entry 1). After screening various
reaction conditions, we found that beneficial effects were
observed in the presence of molecular sieves 4A (MS4A)
1
-8).
A kinetic study was carried out in order to examine
the mechanism of this system using methyl p-tolyl sulfide
as a model substrate. The results are shown in Figure
2
(entry 3). Although the role of MS4A is not clear at
. Enantiomeric excess of the sulfoxide largely depended
present, we consider that it plays an important role in
the formation of the reactive Ti(IV)-diol 1 complex. In
addition, the use of cumyl hydroperoxide instead of tert-
butyl hydroperoxide improved greatly the enantiomeric
excess (entry 4). The solvent showed a marked effect on
on reaction time. For example, at the initial stage of the
reaction the sulfoxide was obtained in 40% ee (5 h, 20%
yield), and after 30 h enantiomeric excess of the product
increased to 95% ee (42% yield). These facts indicate that
kinetic resolution14 of the sulfoxide may follow the
asymmetric oxidation. Accordingly, we next examined
the enantioselective oxidation of racemic methyl p-tolyl
sulfoxide with this chiral titanium-(3S,4S)-1 complex as
a chiral catalyst at -20 °C. The relationship between
optical yield and conversion of sulfoxide is shown in
Figure 3. The optical purity of the sulfoxide increased
(
12) (a) Pitchen, P.; Kagan, H. B. Tetrahedron Lett. 1984, 25, 1049.
(
b) Pitchen, P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B. J . Am.
Chem. Soc. 1984, 106, 8188. (c) Kagan, H. B.; Dunach, E.; Nemecek,
C.; Pitchen, P.; Samuel, O.; Zhao, S. Pure. Appl. Chem. 1985, 57, 1911.
(d) Zhao, S.; Samuel, O.; Kagan, H. B. Tetrahedron 1987, 43, 5135. (e)
Zhao, S.; Samuel, O.; Kagan, H. B. Org. Synth. 1989, 68, 49. (f) Brunel,
J . M.; Diter, P.; Duetsch, M.; Kagan, H. B. J . Org. Chem. 1995, 60,
8
086. (g) Brunel, J . M.; Kagan, H. B. Synlett 1996, 405. (h) Brunel,
J . M.; Kagan, H. B. Bull. Soc. Chim. Fr. 1996, 133, 1109. (i) Furia, F.
D.; Modena, G.; Seraglia, R. Synthesis 1984, 325. (j) Komatsu, N.;
Hashizume, M.; Sugita, T.; Uemura, S. Tetrahedron Lett. 1992, 33,
(13) (a) Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J . Org.
Chem. 1993, 58, 7624. (b) Scettri, A.; Bonadies, F.; Lattanzi, A.;
Senatore, A.; Soriente, A. Tetrahedron: Asymmetry 1996, 7, 657.
(14) (a) Kagan, H. B.; Fiaud, J . C. Kinetic Resolution. In Topics in
Stereochemistry; Allinger, N. L., Eliel, E. L., Eds.; Interscience: New
York, 1987; Vol. 14, p 249. (b) Eliel, E. L.; Wilen, S. H.; Mander, L.
M. Stereochemistry of Organic Compounds; Wiley-Interscience: New
York, 1994; pp 395-415.
5
391. (k) Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J . Org.
Chem. 1993, 58, 4529. (l) Hutton, C. A.; White, J . M. Tetrahedron
Lett. 1997, 38, 1643. (m) Yamamoto, K.; Ando, H.; Shuetake, T.;
Chikamatsu, H. J . Chem. Soc., Chem. Commun. 1989, 754. (n) Quite
recently, Rosini et al. reported that the Ti(IV)/(S,S)-hydrobenzoin/H
2
O
system was efficient for asymmetric oxidation of sulfides. Superchi,
S.; Rosini, C. Tetrahedron: Asymmetry 1997, 8, 349.

8
562 J . Org. Chem., Vol. 62, No. 24, 1997
Ta ble 1. Asym m etr ic Oxid a tion of Meth yl p-Tolyl Su lfid ea
Notes
sulfoxide
yield (%)b
sulfone
entry
ROOH
solvent
time (h)
additive
ee (%)c
yield (%)
1
2
3
4
5
TBHPd
TBHP
TBHP
CHP
CHP
toluene
toluene
toluene
toluene
CH2Cl2
30
30
30
30
90
-
70
66
69
42
75
10
14
30
95
41
10
8
14
40
14
H2Of
MS4Ag
MS4A
MS4A
e
a
Sulfide (0.5 mmol), Ti(O Pr)4 (0.025 mmol), (3S,4S)-1 (0.05 mmol). Isolated yield. c Enantiomeric excess was determined by HPLC
i
b
analysis. tert-Butyl hydroperoxide. Cumyl hydroperoxide. f H2O (1 mmol) was added. g MS4A (70 mg) was added.
d
e
Ta ble 2. Asym m etr ic Oxid a tion of Su lfid es to Su lfoxid esa
sulfoxide
sulfone
entry
R1
p-tolyl
Ph
Ph
R2
time (h)
yield (%)b
ee (%)c
configd
yield (%)b
1
2
3
4
5
6
7
8
9
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
30
30
35
55
40
30
60
40
15
25
42
36
40
58
92
30
45
46
80
83
95
87
82
65
33
40
87
80
3
(S)
(S)
(S)
(-)
(-)
(-)
(S)
(S)
(S)
(-)
40
45
51
40
-
55
40
48
p-BrC6H4
o-BrC6H4
p-MeOC6H4
o-MeOC6H4
2-naphthyl
benzyl
trace
trace
n
1
0
octyl
<1
a
Sulfide (0.5 mmol), Ti(O Pr)4 (0.025 mmol), (3S,4S)-1 (0.05 mmol). Isolated yield. c Enantiomeric excess was determined by HPLC
i
b
d
11-13
analysis. Absolute configurations were determined by comparison of the sign of [R]D to literature values.
F igu r e 2. Dependence of yield of products [methyl p-tolyl
sulfoxide (2); methyl p-tolyl sulfone (9)] and optical yield of
methyl p-tolyl sulfoxide (O) on the time (h) in the enantiose-
lective oxidation of methyl p-tolyl sulfide.
F igu r e 3. Kinetic resolution of methyl p-tolyl sulfoxide.
of this catalyst with cumyl hydroperoxide can form
intermediate 4 which reacts with sulfides to afford optical
active sulfoxides. However, this catalytic activity is also
promoted by the accompanying oxidation of the resulting
sulfoxides to sulfone by virtue of coordination of sulfoxide
to Ti(IV). A combination of asymmetric oxidation and
kinetic resolution gave the sulfoxide in high optical
purity.
as the preferential oxidation of the R-isomer to sulfone
took place. The relative rate of oxidation of enantiomers,
k
R
/k
S
, was determined to be ca. 3.0 according to the
1
4a
reported equation.
Although the mechanistic details of this reaction are
not yet clear, we presume the presence of a mononuclear
titanium with two diol ligands as a catalyst. Reaction

Notes
J . Org. Chem., Vol. 62, No. 24, 1997 8563
2
5
p h ola n e (2): colorless cubes; mp 106.5-107.5 °C; [R]
c 1.05, CHCl ); IR (KBr) 2950, 2420, 2380, 2350, 1480, 1370
cm ; H NMR (400 MHz, CDCl ) δ 0.81-1.16 (7H, m), 0.82 (3H,
d, J ) 7.1 Hz), 0.89 (3H, d, J ) 6.8 Hz), 0.92 (3H, d, J ) 6.6 Hz),
.98 (3H, d, J ) 8.3 Hz), 1.25-1.27 (1H, m), 1.46 (1H, m), 1.65
2H, m), 2.02 (1H, m), 2.17 (1H, m), 4.03-4.12 (2H, m), 4.26-
D
-102.8°
(
3
-1 1
3
0
(
4
2
.29 (1H, m); 13C NMR (100 MHz, CDCl
5.6, 25.9, 26.3, 31.5, 34.1, 34.4, 35.1 (d, J ) 2.5 Hz), 43.2, 48.4
3
) δ 16.2, 20.8, 22.0, 23.2,
(
d, J ) 5.8 Hz), 80.3, 87.8 (d, J ) 6.6 Hz), 88.2 (d, J ) 7.4 Hz);
EI MS m/z 370 (M - 2H). Anal. Calcd for C20 P: C,
4.52; H, 11.37. Found: C, 64.82; H, 11.65.
-Bor a n a t o-(1′R,2′S,5′R)-((2′-Isop r op yl-5′-m et h ylcyclo-
h e x y l)o x y )-(4R ,5R )-4,5-d i-t er t -b u t y l-1,3,2-d io x a p h o s -
H
42BO
3
6
2
In conclusion, we prepared enantiopure 2,2,5,5-tetram-
1
6
ethyl-3,4-hexanediol (1) via the diastereomeric phos-
phine-boranes 2 and 3. This chiral diol 1 has been
proved useful as an effective chiral ligand in catalytic
enantioselective oxidation of sulfides to sulfoxides.
p h ola n e (3): colorless plates; mp 84.5-85.5 °C; [R]
c 1.04, CHCl ); IR (KBr) 2950, 2440, 2390, 2350, 1480, 1370
cm ; H NMR (400 MHz, CDCl ) δ 0.84-2.08 (12H, m), 0.85
3H, d, J ) 7.1 Hz), 0.90 (3H, d, J ) 3.4 Hz), 0.92 (3H, d, J )
D
+13.3°
(
3
-
1
1
3
(
13
2
.7 Hz), 0.98 (18H, d, J ) 5.6 Hz), 4.02-4.13 (3H, m); C NMR
) δ 16.1, 21.0, 22.0, 22.9, 25.7, 25.9, 26.1, 31.5,
34.0, 34.4, 35.2 (d, J ) 3.3 Hz), 43.2, 48.4 (d, J ) 5.0 Hz), 80.6
d, J ) 2.9 Hz), 88.0 (d, J ) 7.4 Hz), 88.1 (d, J ) 6.6 Hz); FABMS
m/z 369 (M - 3H). Anal. Calcd for C20 P: C, 64.52; H,
(100 MHz, CDCl
3
Exp er im en ta l Section
(
Melting points were determined in open capillaries using a
Yamato micro melting point apparatus and were uncorrected.
H
42BO
3
1
1.37. Found: C, 64.75; H, 11.31.
1
13
H NMR and C NMR spectra were recorded using a J EOL
X-r a y Cr ysta llogr a p h ic An a lysis of Com p ou n d 2.17
A
1
13
GSX-400 instrument ( H at 400 MHz and C at 100 MHz). IR
spectra were recorded on a Hitachi IR 215 spectrophotometer.
Optical rotations were measured with a J ASCO DIP-370 digital
polarimeter with 1-dm-long cell. Optical purities were deter-
mined by HPLC analysis performed on a Hitachi L-6000 pump
and Hitachi L-4000 UV detector with an appropriate chiral
column. Recycling preparative HPLC was performed on J AI LC-
well-shaped orthorhombic crystal of 2 was obtained by recrys-
tallization from methanol: C20H42BO P; space group P2 2 2
3 1 1 1
-3
(
#19); Z ) 4; D ) 1.035 g/cm ; cell constants a ) 10.727(5) Å,
3
b ) 23.211(4) Å, c ) 9.600(2) Å, V ) 2390(1) Å ; temperature of
data collection 300 K; 1306 unique reflections (I > 3.00σ(I)); R
)
(
(
0.070, Rw ) 0.086. Selected bond distances (Å) and angles
deg): P(1)-B(1) 1.87(1), P(1)-O(1) 1.591(5), P(1)-O(2) 1.600-
5), P(1)-O(3) 1.566(6), O(1)-P(1)-B(1) 116.4(4), O(2)-P(1)-
9
08 and RI Detector RI-5. Mass spectra were obtained on J EOL
J MS-HX110. Microanalysis were performed on a Perkin-Elmer
40B at the Chemical Analysis Center of Chiba University.
B(1) 117.7(4), O(3)-P(1)-B(1) 113.9(4), O(2)-P(1)-O(3) 102.4(3),
O(1)-P(1)-O(3) 108.1(3), O(1)-P(1)-O(2) 96.2(3).
2
Tetrahydrofuran (THF) was distilled from sodium benzophenone
ketyl under argon prior to use. Toluene and methylene chloride
were distilled from CaH and stored over molecular sieves 4A.
2
Titanium(IV) tetraisopropoxide was distilled before use. Dichrolo-
P r ep a r a tion of En a n tiom er ica lly P u r e 2,2,5,5-Tetr a m -
eth yl-3,4-h exa n ed iol fr om P h osp h in e-Bor a n es 2 a n d 3.
Diastereomerically pure 2 (3.7 g, 10 mmol) in toluene (50 mL)
2
was treated with MeLi (33 mL of 1.5 M Et O solution, 50 mmol)
(
l-menthyloxy)phosphine was prepared by reaction of lithium
at rt for 5 h. The reaction mixture was poured into vigorously
stirred water. The organic layer was separated, and the aqueous
layer was extracted with ethyl acetate three times. The
1
0c
l-menthoxide with PCl (bp 105 °C/2 mmHg; lit. 120-122 °C/3
3
mmHg). 2-Naphthyl methyl sulfide, o-bromophenyl methyl
sulfide, o-anisyl methyl sulfide, and p-anisyl methyl sulfide were
prepared from the corresponding thiophenol derivatives by
methylation with iodomethane in the presence of DBU.15 tert-
Butyl hydroperoxide (5.0-6.0 M decane solution) was purchased
from Aldrich, and cumyl hydroperoxide was obtained as a gift
from NOF Corporation. All experiments were carried out under
argon atmosphere. The products were isolated by preparative
TLC on silica gel (Wakogel B-5F) or column chromatography on
silica gel (Wakogel C-200).
combined extracts were washed with brine and dried over Na
SO . The solvent was evaporated under reduced pressure, and
the residue was purified by flash column chromatography
CHCl ) to give crude (3S,4S)-1 as a white powder (1.7 g, 95%).
It was recrystallized from hexane to afford enantiomerically pure
3S,4S)-1 as colorless needles. In a similar manner, enantio-
merically pure antipode (3R,4R)-1 was obtained from 3 (1.6 g,
0%).
3S,4S)-2,2,5,5-Tet r a m et h yl-3,4-h exa n ed iol:
2
-
4
(
3
(
9
(
colorless
+4.1° (c 1.06, CHCl ); IR
KBr) 3360, 2950, 2920, 2860, 1480, 1410, 1360, cm ; H NMR
P r ep a r a tion of Dia ster eom er ica lly P u r e P h osp h in e-
Bor a n es 2 a n d 3. To a solution of dl-2,2,5,5-tetramethyl-3,4-
hexanediol (8.7 g, 50 mmol) in THF was added n-BuLi (61 mL
of 1.63 M hexane solution, 100 mmol) at 0 °C. The mixture was
added to a solution of dichloro(l-menthyloxy)phosphine (12.1 g,
25
needles; mp 146.0-147.5 °C; [R]
D
3
-1
1
(
(
13
400 MHz, CDCl
NMR (100 MHz, CDCl
Anal. Calcd for C10
H, 13.02.
3
) δ 0.92 (18H, s), 2.35 (2H, d), 3.30 (2H, d);
C
+
3
) δ 25.8, 35.2, 74.9; FABMS m/z 174 (M ).
H O : C, 68.92; H, 12.72. Found: C, 69.14;
22 2
5
0 mmol) in THF at -78 °C, and the reaction mixture was
warmed to rt. The flask was immersed in an ice-water bath
and then BH -THF (50 mL of 1.0 M THF solution, 50 mmol)
(
3R,4R)-2,2,5,5-Tet r a m et h yl-3,4-h exa n ed iol:
colorless
-4.3° (c 0.95, CHCl ); IR
KBr) 3360, 2950, 2920, 2860, 1480, 1410, 1360 cm ; H NMR
3
1
4
needles; mp 146.0-148.0 °C; [R]
D
3
was added. The reaction mixture was slowly added to vigorously
stirred water. The organic layer was separated, and the aqueous
layer was extracted with ethyl acetate three times. The
-
1 1
(
(
1
3
400 MHz, CDCl
3
) δ 0.92 (18H, s), 2.38 (2H, d), 3.33 (2H, d);
C
+
NMR (100 MHz, CDCl ) δ 25.8, 35.2, 74.9; FABMS m/z 174 (M ).
HRMS calcd for C10H O m/z 174.1620, found m/z 174.1633.
3
2 4
combined extracts were washed with brine and dried (Na SO ).
22 2
The solvent was evaporated under reduced pressure, and the
residue was dissolved in hexane. The solution was passed
through a short column packed with silica gel (hexane/ethyl
acetate ) 100/1). The eluent was evaporated to give a mixture
of 2 and 3 as a white powder (15.3 g, 82%). It was recrystallized
from MeOH to give a pure diastereomer 2 (5.0 g). Another
diastereomer 3 was obtained from the mother solution (4.5 g).16
Deter m in a tion of En a n tiom er ic P u r ity of Op tica lly
Active 2,2,5,5-Tetr a m eth yl-3,4-h exa n ed iol. To a solution of
(3S,4S)-2,2,5,5-tetramethyl-3,4-hexanediol (87 mg, 0.5 mmol) in
THF, n-BuLi (0.6 mL of 1.63 M hexane solution, 1 mmol) was
added. The contents were added to a solution of dichlorophe-
nylphosphine (67 µL, 0.5 mmol) in THF at -78 °C. After the
addition, the reaction mixture was warmed to rt. The flask was
2
-Bor a n a t o-(1′R,2′S,5′R)-((2′-Isop r op yl-5′-m et h ylcyclo-
immersed in an ice-water bath, and then BH
3
-THF (0.5 mL of
h e x y l)o x y )-(4S ,5S )-4,5-d i-t er t -b u t y l-1,3,2-d io x a p h o s -
1
.0 M THF solution, 0.5 mmol) was added. The reaction mixture
was poured into vigorously stirred water. The organic layer was
separated, and the aqueous layer was extracted with ethyl
(
15) Ono, N.; Miyake, H.; Saito, T.; Kaji, A. Synthesis 1980, 952.
(16) The mother solution was concentrated under reduced pressure,
and the residue was dissolved in hot MeOH. The solution was seeded
with optically pure diastereopure 3 (ca. 20 mg), which was obtained
by preparative HPLC (ODS) using MeOH as the eluent. It was kept
overnight at room temperature to give 4.5 g of diastereomer 3 as
colorless plates.
(17) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.

8
564 J . Org. Chem., Vol. 62, No. 24, 1997
Notes
acetate three times. The combined extracts were washed with
brine and dried (Na SO ). The solvent was evaporated under
toluene (1 mL) was added in a flask containing MS4A (70 mg)
and (3S,4S)-2,2,5,5,-tetramethyl-3,4-hexanediol (0.05 mmol, 8.9
mg). This solution was stirred for 2 h at rt, and then methyl
p-tolyl sulfide (68 µL, 0.5 mmol) was added. The solution was
cooled to -20 °C, and 80% cumyl hydroperoxide (190 µL, 1 mmol)
was added. After stirring for 30 h at the same temperature,
the reaction was quenched with ca. 10% aqueous solution of
sodium sulfite. The aqueous layer was extracted with ethyl
acetate three times. The combined organic layer was washed
2
4
reduced pressure, and the residue was purified by column
chromatography (hexane/ethyl acetate ) 10/1) to give 2-bo-
ranato-2-phenyl-(4S,5S)-di-tert-butyl-1,3,2-dioxaphospholane as
colorless needles (135 mg, 93%). The enantiomeric excess was
determined to be 100% ee by chiral HPLC analysis: Chiralcel
OJ (Daicel, hexane/2-propanol ) 9/1, flow rate ) 1.00 mL/min):
t
r
(S,S) ) 4.8 min, t
r
(R,R) ) 6.4 min.
(
4S,5S)-2-P h en yl-2-bor a n a to-4,5-d i-ter t-1,3,2-d ioxa p h os-
2 4
with brine and dried over Na SO . The solvent was evaporated
2
0
p h ola n e: colorless needles; mp 139.0-140.0 °C; [R]
c 1.19, CHCl ); IR (KBr) 3000, 2420, 2360, 2330, 1480 cm ; H
NMR (400 MHz, CDCl ) δ 0.68 (9H, s), 1.09 (9H, s), 4.18-4.26
D
-38.8°
under reduced pressure, and column chromatography (ethyl
acetate) on silica gel afforded 32 mg of (S)-methyl p-tolyl
sulfoxide (42%, 95% ee) and 34 mg of methyl p-tolyl sulfone
-
1 1
(
3
3
1
3
(
2
2H, m), 7.26-7.72 (5H, m); C NMR (100 MHz, CDCl
6.5, 34.3, 35.2 (J ) 5.2 Hz), 89.1 (J ) 6.6 Hz), 89.2 (J ) 5.8
3
) δ 26.2,
(40%). The enantiomeric excess was measured by chiral HPLC
analysis using Chiralcel OD-H column. Absolute configuration
was assigned by comparison of the sign of specific rotation with
literature data.1
Hz), 128.3, 129.7, 129.8, 132.0 (J ) 1.7 Hz), 135.0, 135.5; FABMS
m/z 291 (M -3H); HRMS calcd for C16
2
H25BO P m/z 291.1685,
1-13
found m/z 291.1696.
(
4R,5R)-2-P h en yl-2-bor a n a to-4,5-d i-ter t-1,3,2-d ioxa p h os-
2
0
p h ola n e: colorless needles; mp 136.0-138.0 °C; [R]
c 1.09, CHCl ); IR (KBr) 3000, 2420, 2360, 2330, 1480 cm ; H
NMR (400 MHz, CDCl ) δ 0.68 (9H, s), 1.09 (9H, s), 4.18-4.26
D
+39.0°
Ack n ow led gm en t. The authors thank Professor
Kentaro Yamaguchi, Chemical Analysis Center of Chiba
University, and Mr. Masayoshi Nishiura for the X-ray
analysis. We are grateful to NOF Corporation for a
generous gift of cumyl hydrperoxide. This research was
supported by the Ministry of Education, Science, Sports
and Culture, J apan.
-
1 1
(
3
3
1
3
(
2
2H, m), 7.26-7.72 (5H, m); C NMR (100 MHz, CDCl
3
) δ 26.2,
6.5, 34.3, 35.2 (J ) 5.2 Hz), 89.1 (J ) 6.6 Hz), 89.2 (J ) 5.8
Hz), 128.3, 129.7, 129.8, 132.0 (J ) 1.7 Hz), 135.0, 135.5; FABMS
m/z 291 (M - 3H); HRMS calcd for C16
2
H25BO P m/z 291.1685,
found m/z 291.1690.
A Typ ica l Exp er im en ta l P r oced u r e for th e Asym m etr ic
i
Oxid a tion . A solution of Ti( OPr)
4
(7.4 µL, 0.025 mmol) in
J O971004Y