Diastereoselectivity in the reduction of acyclic carbonyl compounds with diisopropoxytitanium(III) tetrahydroborate

Article abstract of DOI:10.1021/jo9902906

Diisopropoxytitanium(III) tetrahydroborate, ((i)PrO)₂TiBH₄, formed in situ in dichloromethane from diisopropoxytitanium dichloride and benzyltriethylammonium tetrahydroborate (1:2) reduces α-hydroxyketones/1,2- diketones and β-hydroxyketones/1,3-diketones to the corresponding diols with high stereoselectivity. In the case of α-hydroxyketones and 1,2-diketones, the anti isomer is the major product while reduction of β-hydroxyketones and 1,3-diketones leads to the syn isomer as the major product.

Full text of DOI:10.1021/jo9902906

J . Org. Chem. 1999, 64, 5841-5844
5841
Dia ster eoselectivity in th e Red u ction of Acyclic Ca r bon yl
Com p ou n d s w ith Diisop r op oxytita n iu m (III) Tetr a h yd r obor a te
K. S. Ravikumar,†,‡ Surajit Sinha,† and S. Chandrasekaran*,†
Department of Organic Chemistry, Indian Institute of Science, Bangalore-560 012, India, and
IDL-Nitro Nobel Basic Research Institute, Sankey Road, Malleswaram, Bangalore-560 012, India
Received February 17, 1999
Diisopropoxytitanium(III) tetrahydroborate, (iPrO)2TiBH4, formed in situ in dichloromethane from
diisopropoxytitanium dichloride and benzyltriethylammonium tetrahydroborate (1:2) reduces
R-hydroxyketones/1,2-diketones and â-hydroxyketones/1,3-diketones to the corresponding diols with
high stereoselectivity. In the case of R-hydroxyketones and 1,2-diketones, the anti isomer is the
major product while reduction of â-hydroxyketones and 1,3-diketones leads to the syn isomer as
the major product.
The development of methods for the diastereoselective
reduction of carbonyl group continues to be of interest
in organic chemistry.1,2 This was prompted by the re-
quirements of modern total synthesis in which a mixture
of diastereomers are avoided, together with enhanced
theoretical understanding of stereoselectivity which al-
lows rationalization of the results.3
To extend the scope of the stereoselective reductions
mediated by tetrahydroborate 1, we studied the reduction
of R-hydroxyketones and 1,2-diketones with 1. A number
of R-hydroxyketones (1 equiv) were treated with the
tetrahydroborate 1 (1 equiv) in CH2Cl2 (-20 °C, 5 min),
and all of them led to the formation of the corresponding
anti-1,2-diols (Table 1).
Recently, we reported that diisopropoxytitanium(III)
tetrahydroborate, (iPrO)2TiBH4, 1,4 can be used for di-
astereoselective5 and chemo- and stereoselective reduc-
tion6 of a number of substrates with representative
functional groups. In this paper, we describe our results
on the highly diastereoselective reduction of R-hydroxy-
ketones/1,2-diketones and â-hydroxyketones/1,3 dike-
tones mediated by tetrahydroborate 1.
However, the anti selectivity was reduced to 83% in
the case of 2c when the substituents R1 and R2 were
n-propyl groups. But, interestingly in the reduction of
substrates 2a and 2b having aryl substituents the anti
selectivity was more than 99%, which is comparable with
the result obtained using Zn(BH4)2 (Table 1).1,7a
Maier8 showed that the reduction of symmetrical 1,2-
diketones using LiBH4 in the presence of TiCl4 resulted
in the formation of the anti isomer as the major product.
When tetrahydroborate 1 (2 equiv) in dry CH2Cl2 was
allowed to react with a number of 1,2-diketones (1 equiv,
-20 °C, 10-45 min), the corresponding anti-1,2-diols
were obtained with a high degree of stereoselectivity. The
results are summarized in Table 2. It is evident from
these results that our method is superior to Maier’s
method.
Red u ction of r-Hyd r oxyk eton es a n d 1,2-Dik e-
ton es. It has been commonly recognized that reduction
of R-hydroxyketones with hydride reagents is generally
anti selective, whereas hydride reduction of R-alkoxyke-
tones is syn selective.7
Zinc borohydride is known to reduce R-hydroxyketones
to the corresponding anti-diols1,7a with good selectivity
via a chelated transition state. Silylation with the bulky
TBDMS group gave the protected derivatives of R-hy-
droxyketones, which were reduced by Red-Al at -78 °C
preferentially to the syn products via a Felkin transition
state. These complementary methods were used to syn-
thesize various diastereomers of a possible fragment of
polyoxygenated antibiotics.7d
Compounds 5a -c having both substituents as aryl
groups underwent reductions with 1 giving excellent anti
selectivity (92-99%). When one of the substituents was
an alkyl group as in the case of diketone 5d , the
stereoselectivity was found to be 80%. In the reaction of
compound 5e having both alkyl substituents the stereo-
selectivity was completely lost. Reduction is presumed
to go through a titanium-mediated transition state, and
the stereochemical course of the reduction is explained
in terms of Cram’s cyclic model,9 which involves the
assistance of a metal counterion to form a rigid cyclic
transition state (Figure 1). When R2 is bulky, the transi-
tion state A leading to the anti isomer is apparently much
favored over B leading to the syn isomer.
† Indian Institute of Science.
‡ IDL-Nitro Nobel Basic Research Institute.
(1) Oishi, T.; Nakata, T. Acc. Chem. Res. 1984, 17, 338.
(2) Trost, B. M.; Fleming, I. Comprehensive Organic Synthesis:
Selectivity, Strategy and Efficiency in Modern Organic Chemistry;
Pergamon Press: Oxford, 1991; Vol. 8, p 1.
(3) Bartlett, P. A. Tetrahedron 1980, 36, 3.
(4) Ravikumar, K. S.; Baskaran, S.; Chandrasekaran, S. J . Org.
Chem. 1993, 58, 5981.
(5) Ravikumar, K. S.; Chandrasekaran, S. J . Org. Chem. 1996, 61,
826.
(6) Ravikumar, K. S.; Chandrasekaran, S. Tetrahedron. 1996, 52,
9137.
(7) (a) Nakata, T.; Tanaka, T.; Oishi, T. Tetrahedron Lett. 1983,
2653. (b) Katzenellenbogen, J . A.; Bowlus, S. B. J . Org. Chem. 1973,
38, 627. (c) Bowlus, S. B.; Katzenellenbogen, J . A. J . Org. Chem. 1974,
39, 3309. (d) Nakata, T.; Fukui, M.; Ohtsuka, H.; Oishi, T. Tetrahedron
Lett. 1983, 2661. (e) Fujita, M.; Hiyama, T. J . Org. Chem. 1988, 53,
5405.
Red u ction of â-Hyd r oxyk eton es a n d 1,3-Dik e-
ton es. The diastereoselective reduction of â-hydroxyke-
tones to the corresponding syn-1,3-diols has great utility
in synthetic organic chemistry due to the occurrence of
(8) Maier, G.; Roth, C.; Schmitt, R. K. Chem. Ber. 1985, 118, 704.
(9) Cram, D. J .; Wilson, D. R. J . Am. Chem. Soc. 1963, 85, 1245.
10.1021/jo9902906 CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/14/1999

5842 J . Org. Chem., Vol. 64, No. 16, 1999
Ravikumar et al.
Ta ble 1.
Ta ble 3.
sub-
entry strate
time
product
yield
(%)
R1
R2
(min) syn-9/anti-10
product
1,7a
1
2
8a
8b
Ph
p-Me-
C6H4
p-MeO- p-MeO-
C6H4 C6H4
Me
Ph
p-Me-
C6H4
5
5
100:-
100:-
95
93
sub-
time syn-3/ yield Zn(BH4)2
entry strate
R1
R2
(min) anti-4
(%)
syn/anti
1
2
2a
2b
Ph
p-MeO- p-MeO-
C6H4 C6H4
n-Pr n-Pr
Ph
5
5
1:99a
1:99
92
90
1:99
3
8c
10
100:-
89
4
5
6
8d
8e
8f
Ph
Et
Et
15
15
15
80:20
73:27
95:5
97
95
92
3
2c
5
17:83
95
1:99
Ph
Et
1H NMR analysis shows a syn/anti ratio of 1:99 and HPLC
a
shows 3:97.
droxyketones with NaBH4/trialkylborane13 or with NaBH4/
alkoxyborane14 in THF required very a low temperature
(-70 °C) and a longer reaction time to yield syn-1,3-diols.
Ta ble 2.
Maier15 studied the reduction of symmetrical diketones
and showed that LiBH4 reduction of 1,3-diketones pro-
duced the anti isomer as the major product but prior
addition of TiCl4 to 1,3-diketones gave the syn isomer.
To realize stereoselectivity in the reduction, the con-
formations of â-hydroxyketones have to be controlled. We
expected that stable chelate complexes of â-hydroxyke-
tones with Ti3+ reagent would be sufficiently rigid to
control the approach of the hydride in an intramolecular
pathway. On the basis of this consideration, we examined
at first the reduction of â-hydroxyketones. The tetrahy-
droborate 1 (1 equiv) in dry CH2Cl2 was allowed to react
with a number of â-hydroxyketones (1 equiv, -20 °C,
5-15 min), and the corresponding syn-1,3-diols were
obtained with a high degree of stereoselectivity. The
results are summarized in Table 3. For example, exclu-
sive (100%) 1,3-syn selectivity was obtained when R1 and
R2 were aromatic groups. However, the syn selectivity
was lowered if one of the substituents was an alkyl group.
Thus, in the reaction of â-hydroxy ketones 8d and 8e with
1 under the reaction conditions the syn selectivity was
only 72-80%. Surprisingly, when both the substituents
were ethyl groups as in substrate 8f the syn selectivity
was very high (95%). In general, the stereoselectivity
obtained in the reduction of â-hydroxy ketones with aryl
substituents is good or better than that achieved using
alkoxydialkylboranes,14 but in the case of some alkyl-
substituted substrates the stereoselectivity obtained with
our reagent is not as good.
product
time syn-6/ yield LiBH4
(min) anti-7 (%) syn/anti
TiCl4 +
8
sub-
entry strate
R1
R2
4
5
5a
5b
Ph
Ph
15
15
4:96#
8:92
94
93
20:80
24:76
p-MeO- p-MeO-
C6H4
o-MeO- Ph
C6H4
C6H4
6
5c
45
1:99
82
7
8
5d
5e
Ph
Me
Me
15
10
20:80
46:54
82
87
Me
1H NMR analysis and HPLC shows syn/anti ratio of 4:96.
a
F igu r e 1.
The syn selectivity in the reduction of â-hydroxyke-
tones can be explained by a model shown in Figure 2.12
During the reduction, the tetrahydroborate 1 may first
react with the â-hydroxy group to give a TiO species
leading to a six-membered ring chelation. Subsequent
intramolecular delivery of hydride from the top face
affords the syn diastereomer, whereas the axial hydrogen
on the R-carbon prevents the approach of the reducing
agent from the bottom face.
these fragments in biologically active natural products.10
Many reagents have been developed for the reduction of
â-hydroxyketones to syn-1,3-diols.11,12 Reduction of â-hy-
(10) (a) Ma, P.; Martin, V. S.; Masamune, S.; Sharpless, K. B.; Vitti,
S. M. J . Org. Chem. 1982, 47, 1378. (b) Lipshutz, B. H.; Kozlowski, J .
A. J . Org. Chem. 1984, 49, 1147. (c) Kiyooka, S. I.; Sasaoka, H.;
Fujiyama, R.; Heathcock, C. H. Tetrahedron Lett. 1984, 25, 5331.
(11) Kathawala, F. G.; Prager, B.; Prasad, K.; Repic, O.; Shapiro,
M. J .; Stabler, R. S.; Widler, L. Helv. Chim. Acta 1986, 69, 803.
(12) (a) Kiyooka, S.; Kuroda, H.; Shimasaki, Y. Tetrahedron Lett.
1986, 27, 3009. (b) Sarko, C. R.; Collibee, S. E.; Knorr, A. L.; DiMare,
M. J . Org. Chem. 1996, 61, 868.
(13) Narasaka, K.; Pai, F. C. Tetrahedron 1984, 40, 2233.
(14) Chen, K. M.; Hardtman, G. E.; Prasad, K.; Repic, O. Tetrahe-
dron Lett. 1987, 28, 155.
(15) Maier, G.; Schmitt, R. K.; Seipp, U. Chem. Ber. 1985, 118, 722.

Reduction of Acyclic Carbonyl Compounds
J . Org. Chem., Vol. 64, No. 16, 1999 5843
Exp er im en ta l Section
1
Gen er a l Rem a r k s. H NMR spectra were recorded at 90,
200, 270, and 300 MHz in CDCl3. TLC were performed on 0.25
mm precoated silica plates (60F-254). All the products were
purified by flash column chromatography on silica gel. HPLC
analysis was performed using a normal-phase silica column
(5 µm, length ) 25 cm). The melting points are uncorrected.
A stock solution of diisopropoxytitanium(III) dichloride in dry
CH2Cl2 (11.8% w/v) was used.16 Benzyltriethylammonium
tetrahydroborate was prepared according to the literature
procedure.5
F igu r e 2. syn-1,3-diol.
Ta ble 4.
Gen er a l P r oced u r e for th e P r ep a r a tion of Diisop r o-
p oxytita n iu m (III) Tetr a h yd r obor a te, 1 (2 m m ol). To a
stirred solution of (iPrO)2TiCl2 (4 mL, 2 mmol) was slowly
added benzyltriethylammonium tetrahydroborate (0.828 g, 4
mmol) in dry CH2Cl2 (8 mL) under N2 at -20 °C. The reaction
mixture was stirred for 30 min, and this solution was used as
such for reductions.
P r ep a r a tion of r-Hyd r oxyk eton es a n d 1,2-Dik eton es.
Benzoin,17 4,4′-dimethoxybenzoin,17 butyroin,18 benzil,19 4,4′-
dimethoxybenzil,19 2-methoxybenzil,20 and 1-phenyl-1,2-pro-
panedione21 were prepared according to the literature proce-
dure. Biacetyl was purchased from Aldrich and purified using
steam distillation before use.
product
TiCl4 +
15
sub-
entry strate
time syn-12/ yield LiBH4
R′ (min) anti-13 (%) syn/anti
R
7
8
9
11a
11b
11c
Me
Ph
Me
Me
15
120
120
46:54
88:12
85:15
92
82
79
88:12
92:8
85:15
Gen er a l P r oced u r e for th e Red u ction of r-Hyd r oxy-
k eton es. The R-hydroxy ketone 2a (0.392 g, 2 mmol) in dry
CH2Cl2 (2 mL) was added into a stirred solution of 1 (2 mmol)
at -20 °C, and the reaction mixture was stirred for 5 min at
the same temperature. A solution of saturated K2CO3 (10 mL)
was added and stirred for an additional 15 min (25 °C). The
reaction mixture was extracted with ether (3 × 20 mL), and
it was washed with brine and dried (Na2SO4). Removal of
solvent followed by flash chromatography on silica gel (ether-
petroleum ether 30:70) afforded the diastereomeric (syn/anti)
mixture of 1,2-diphenyl-1,2-ethandiol (3a /4a ) as a colorless
solid and was found to be identical with an authentic sample.
1H NMR analysis of the product 3a /4a 22a,15 (0.394 g, 92%)
shows a syn/anti ratio of 1:99, and HPLC shows 3:97 (petro-
leum ether, flow rate 0.4 mL/min, retention time 9.75 and 9.21
p-MeO- Me
C6H4
1
respectively). IR (thin film): 3330 cm-1. H NMR (CDCl3): δ
4.68 (s, 1H), 4.84 (s, 1H).
syn - an d a n ti-1,2-Bis(4-m eth oxyph en yl)-1,2-eth an ediol,
3b/4b.15,22a Yield: 0.493 g, 90%. Mp: 167 °C (lit.22a mp 164
°C) (syn/anti ) 1:99). IR (thin film): 3300 cm-1
(CDCl3): δ 4.55 (s, 1H), 4.70 (s, 1H).
.
1H NMR
F igu r e 3.
syn - a n d a n ti-4,5-Octa n ed iol, 3c/4c.7b Yield: 0.274 g, 95%
1
(syn/anti ) 17:83). IR (neat): 3340 cm-1. H NMR (CDCl3): δ
The results of the reduction of 1,3-diketones, containing
gem-dimethyl groups, are given in Table 4. In this case,
the selectivity is reduced in comparison to â-hydroxyke-
tones and can be explained on the basis of two possible
chairlike conformations as shown in Figure 3.15 In this
case, the conformation C causes steric hindrance involv-
ing the substituents R and R′. Therefore, the selectivity
largely depends on the substituents (R and R′). When
both are methyl groups, the interactions are relieved in
the conformation D, and therefore, the formation of the
anti isomer is preferred more than syn isomer. Although
the conformer C predominates at equilibrium, in the case
of substrates 11b and 11c the phenyl ring can align itself
in the pseudoaxial position without significant 1,3-diaxial
interaction. However, the selectivity is reduced since it
is not as rigid as in the reduction of â-hydroxy carbonyl
compounds.
3.37 (m, 1H), 3.56 (m, 1H). 13C NMR (CDCl3): δ 71.6, 74.3.
Gen er a l P r oced u r e for th e Red u ction of 1,2-Dik e-
ton es. To a stirred solution of tetrahydroborate 1 (2 mmol)
was added R-dione 5a (0.21 g, 1 mmol) in dry CH2Cl2 (2 mL),
and the reaction mixture was stirred for 15 min at -20 °C. A
solution of saturated K2CO3 (10 mL) was added and the
mixture stirred for an additional 15 min (25 °C). The reaction
mixture was extracted with ether (3 × 20 mL), and it was
washed with brine and dried (Na2SO4). Removal of solvent
(16) (a) Dijkgraaf, C.; Rousseau, J . P. G. Spectrochim. Acta 1968,
24A, 1213. (b) Reetz, M. T.; Steinbach, R.; Kebeler, K. Angew. Chem.,
Suppl. 1982, 1899.
(17) Vogel,s Textbook of Practical Organic Chemistry, 5th ed.; ELBS
& Longman: Singapore, 1989; p 1044.
(18) Snell, J . M.; McElvain, S. M. Organic Syntheses; Wiley: New
York, 1943; Collect. Vol. II, p 114.
(19) (a) Vogel,s Textbook of Practical Organic Chemistry, 5th ed.;
ELBS & Longman: Singapore, 1989; p 1045. (b) Wasserman, H.
H.; Ives, J . L. J . Org. Chem. 1985, 50, 3573.
In all the reductions discussed above we believe that
the hydride delivery with our reagent takes place in an
intramolecular fashion. This is based on the observation
that the stereoselectivities achieved in our reaction are
generally greater than those obtained by Maier8,15 involv-
ing the use of LiBH4/TiCl4sreactions that clearly involve
intermolecular hydride delivery to a chelated keto alcohol-
titanium complex.
(20) (a) Asahira, Y.; Terasaka, M. J . Pharm. Soc. J pn. 1923, 494,
219. (b) Asahira, Y.; Ishidate, M. J . Pharm. Soc. J pn. 1925, 521, 624.
(21) (a) Vogel,s Textbook of Practical Organic Chemistry, 5th ed.;
ELBS & Longman: Singapore, 1989; p 1009. (b) Hartung, W. H.;
Crossley, F. Organic Syntheses; Wiley: New York, 1943; Collect. Vol.
II, p 363. (c) Hartman, W. W.; Roll, L. J . Organic Syntheses; Wiley:
New York, 1955; Collect. Vol. III, p 20.
(22) (a) Imuta, M.; Ziffer, H. J . Org. Chem. 1978, 43, 3319. (b)
Yamamoto, K.; Hiroyuki, A.; Takashi, S.; Hiroaki, C. Chem. Commun.
1989, 754.

5844 J . Org. Chem., Vol. 64, No. 16, 1999
Ravikumar et al.
followed by flash chromatography on silica gel (ether-
petroleum ether 30:70) afforded the diastereomeric mixture
of 1,2-diphenylethane-1,2-diol 6a /7a as a colorless solid and
reaction mixture was extracted with ether (3 × 20 mL), and
it was washed with brine and dried (anhyd Na2SO4). Removal
of solvent followed by flash chromatography on silica gel
(ether-petroleum ether 30:70) afforded 1,3-diol 9a /10a 14 (0.432
g, 95%). Mp: 106-107 °C (lit.10c mp (meso) 106-107 °C), only
1
was found to be identical with an authentic sample. H NMR
analysis and HPLC (petroleum ether, flow rate 0.3 mL/min,
retention time 13.24 and 12.54, respectively) of the product
6a /7a 22a,15 (0.196 g, 92%) showed a syn/ anti ratio of 4:96.
syn isomer. IR (thin film): 3240 cm-1 1H NMR (CDCl3): δ
.
1.97 (dt, J ) 14.6, 2.9 Hz, 1H), 2.16 (m, 1H), 3.38 (br s, 2H),
5.03 (dd, J ) 10.1, 2.7 Hz, 2H), 7.2-7.4 (m, 10H). 13C NMR
(CDCl3): δ 47.4, 74.7, 125.6, 127.5, 128.3, 144.0.
syn -
a n d
a n ti-1-(2-Meth oxyp h en yl)-2-p h en yl-1,2-
eth a n ed iol, 6c/7c.22b Yield: 0.199 g, 82% (syn/anti ) 1:99).
IR (thin film): 3350 cm-1. H NMR (CDCl3): δ 2.65-2.95 (br,
1
syn -1,3-Bis(4-m et h ylp h en yl)-1,3-p r op a n ed iol, 9b /10b .
s, 2H), 3.69 (s, 3H), 4.92 (d, J ) 5.5 Hz, 1H), 5.15 (d, J ) 5.4
Hz, 1H), 6.80-6.91 (m, 2H), 7.1-7.3 (m, 7H). 13C NMR
(CDCl3): δ 55.2, 73.2, 76.5, 110.1, 120.4, 127.1, 127.4, 128.1,
128.4, 140.0, 156.4. MS (m/z): 227 [(M+ + 1) - H2O], 137, 121,
107, 77, 65, 51, 39.
Yield: 0.478 g, 93%. Mp: 61 °C, only syn isomer. IR (thin
1
film): 3340 cm-1. H NMR (CDCl3): δ 1.91 (dt, J ) 14.6, 3.0
Hz, 1H), 2.11 (m, 1H), 2.3 (s, 6H), 3.36 (br, 2H), 4.96 (dd, J )
10.0, 2.9 Hz, 2H), 7.11-7.27 (m, 8H). 13C NMR (CDCl3): δ 21.0,
47.3, 74.5, 125.6, 129.0, 137.1, 141.2. MS m/z (rel intensity)
237 [(M+ - H2O), 25], 222 (9), 189 (5), 147 (9), 118 (100), 105
(9), 91 (23), 77 (13).
syn - a n d a n ti-1-P h en yl-1,2-p r op a n ed iol, 6d /7d .7c Yield:
0.125 g, 82% (syn/ anti ) 20:80). IR (thin film): ν 3300 cm-1
.
1H NMR (CDCl3): δ 0.96 (d, J ) 6.4 Hz, 3H), 0.99 (d, J ) 6.5
Hz, 3H), 3.81 (m, 1H), 3.94 (m, 1H), 4.28 (d, J ) 7.7 Hz, 1H),
4.64 (d, J ) 3.9 Hz, 1H). 13C NMR (CDCl3): δ 16.6, 18.5, 71.2,
72.0, 77.1, 79.3.
syn -1,3-Bis(4-m eth oxyp h en yl)-1,3-p r op a n ed iol, 9c/10c.
Yield: 0.51 g, 89%. Mp: 80 °C, only syn isomer. IR (thin
film): 3400 cm-1 1H NMR (CDCl3): δ 1.64 (br s, 1H), 1.91
.
(dt, J ) 14.5,2.9 Hz, 2H), 3.80 (s, 6H), 4.96 (dd, J ) 10.1, 2.7
syn - a n d a n ti-2,3-Bu ta n ed iol, 6e/7e.8 Yield: 0.078 g, 87%
Hz), 6.84-7.32 (m, 8H). 13C NMR (CDCl3): δ 47.5, 55.2, 74.4,
(syn/ anti ) 46:54). IR (neat): 3350 cm-1 1H NMR (CDCl3):
.
113.8, 126.9, 136.5, 158.9. MS m/z (rel intensity) 287 [(M+
1), 2.4], 269 (13), 205 (3), 180 (4), 151 (5), 134 (100), 119 (11),
109 (14), 91 (10), 77 (15).
-
δ 1.10 (d, J ) 6.3 Hz, 3H), 1.14 (d, J ) 5.4 Hz, 3H), 3.48 (m,
1H), 3.76 (m, 1H). 13C NMR (CDCl3): δ 16.80, 19.2, 70.8, 72.4.
P r ep a r a tion of â-Hyd r oxyca r bon yl Com p ou n d s. â-Hy-
droxycarbonyl compounds were prepared according to the
literature procedure.23
syn - a n d a n ti-1-P h en yl-1,3-bu ta n ed iol, 9d /10d .12 Yield:
0.317 g, 97% (syn/ anti ) 80:20). IR (thin film): 3320 cm-1
.
1H NMR (CDCl3): δ 1.23 (d, J ) 6.2 Hz, 3H), 1.24 (d, J ) 6.1
Hz, 3H), 4.94 (dd, J ) 9.7, 9.5 Hz, 1H), 5.06 (dd, J ) 7.0, 6.8
Hz, 1H). 13C NMR (CDCl3): δ 64.5, 67.9, 70.7, 74.1.
1,3-Dip h en yl-1-h yd r oxy-3-p r op a n on e, 8a .24 Yield: 2.08
g, 92%. Mp: 44-45 °C (lit.24 mp 44-46 °C). IR (thin film): ν
3450, 1670, 1600, 1580 cm-1 1H NMR (CDCl3): δ 1.7 (br s,
.
syn - a n d a n ti-1-P h en yl-1,3-p en ta n ed iol, 9e/10e.26
Yield: 0.341 g, 95% (syn/ anti ) 73:27). IR (thin film): 3300
1H), 3.35 (d, J ) 5.5 Hz, 1H), 3.60 (d, J ) 3.3 Hz, 1H), 5.35
(dt, J ) 6.4, 2.7 Hz, 1H), 7.2-7.61 (m, 8H), 7.8-8.1 (m, 2H).
1,3-Bis(4-m eth ylp h en yl)-1-h yd r oxy-3-p r op a n on e, 8b.24
Yield: 1.09 g, 86%. Mp: 45 °C. IR (thin film): 3450, 1675,
1
cm-1. H NMR (CDCl3): δ 4.95 (dd, J ) 6.4, 6.6 Hz, 1H), 5.07
(dd, J ) 4.2, 4.1 Hz, 1H). 13C NMR (CDCl3): δ 69.8, 70.9, 73.3,
1
1605, 1575 cm-1. H NMR (CDCl3): δ 2.3 (s, 3H), 2.4 (s, 3H),
74.5.
syn - a n d a n ti-Hep ta n e-3,5-d iol, 9f/10f.27 Yield: 0.243 g,
3.3 (d, J ) 6.4 Hz, 2H), 3.6 (br s, 1H), 5.25 (dt, J ) 5.7, 1.8 Hz,
1H), 7.1-7.4 (m, 6H), 7.75-7.95 (m, 2H).
92% (syn/ anti ) 95:5). IR (neat): 3350 cm-1
(CDCl3): δ 3.6-3.9 (m), 4.0-4.2 (m).
.
1H NMR
1,3-Bis(4-m eth oxyph en yl)-1-h ydr oxy-3-pr opan on e, 8c.24
Yield: 1.29 g, 90%. Mp: 101-103 °C. IR (thin film): 3500,
P r ep a r a tion of 1,3-Dik eton es. 11a ,28 11b,29 and 11c29
1675 cm-1 1H NMR (CDCl3): δ 3.3 (m, 2H), 3.65 (br s, 1H),
.
were prepared according to the literature procedure.
3.80 (s, 3H), 3.85 (s, 3H), 5.25 (dt, J ) 6.1, 2.0 Hz, 1H), 6.8-
7.0 (m, 4H), 7.25-7.45 (m, 2H), 7.85-8.00 (m, 2H).
Gen er a l P r oced u r e for t h e R ed u ct ion of 1,3-Dion es
w ith 1. To a stirred solution of tetrahydroborate 1 (2 mmol)
was added 1,3-diketone 11a (0.100 g, 1 mmol) in dry CH2Cl2
(2 mL), and the reaction mixture was stirred for 15 min at
-20 °C. A solution of saturated K2CO3 (10 mL) was added and
the mixture stirred for an additional 15 min (25 °C). The
reaction mixture was extracted with ether (3 × 20 mL), and
it was washed with brine and dried (anhy. Na2SO4). Removal
of solvent followed by flash chromatography on silica gel
afforded the diastereomeric (syn/ anti) mixture of 1,3-diol 12a /
1-P h en yl-1-h yd r oxy-3-bu ta n on e, 8d .25 Yield: 0.344 g,
42%. IR (neat): 3380, 1695, 1595 cm-1 1H NMR (CDCl3): δ
.
2.15 (s, 3H), 2.74 (dd, J ) 13.0, 2.6 Hz, 1H), 2.85 (dd, J )
13.0, 6.6 Hz, 1H), 3.41 (br, 1H), 5.10 (dd, J ) 6.5, 2.4 Hz, 1H),
7.20-7.32 (m, 5H).
1-P h en yl-3-h yd r oxy-1-p en ta n on e, 8e.25 Yield: 0.516 g,
1
58%. IR (neat): 3420, 1650 cm-1. H NMR (CDCl3): δ 1.05 (t,
J ) 6.3 Hz, 3H), 1.60 (qd, J ) 6.3, 1.3 Hz, 2H), 2.65 (br s, 1H),
3.05 (d, J ) 6.3 Hz, 1H), 3.10 (d, J ) 1.3 Hz, 1H), 4.15 (m,
1H), 7.4-7.6 (m, 3H), 7.8-8.1 (m, 2H).
13a 8 (0.123 g, 92%) in a 46:54 ratio. IR (thin film): 3350 cm-1
.
1H NMR (CDCl3): δ 0.70 (s, 3H), 0.87 (s, 6H), 0.89 (s, 3H). 13
NMR (CDCl3): δ 39.9, 40.40, 74.0, 76.6.
C
3-Hyd r oxyh ep ta n -5-on e, 8f.25 Yield: 0.676 g, 52%. IR
(neat): 3400, 1700 cm-1. 1H NMR (CDCl3): δ 1.05 (t, 6H), 1.3-
1.7 (qd, 2H), 2.15 (s, 1H), 2.2-2.5 (m, 2H), 2.6 (d, 2H), 3.8-
4.2 (m, 1H).
2,2-Dim eth yl-1,3-d ip h en yl-1,3-p r op a n ed iol, 12b/13b.8
Yield: 0.137 g, 82% (based on starting material recovery of
0.088 g, syn/ anti ) 88:12). IR (thin film): 3350, 1610 cm-1
.
Gen er a l P r oced u r e for th e Red u ction of â-Hyd r oxy-
k eton es. The â-hydroxyketone 8a (0.452 g, 2 mmol) in dry
CH2Cl2 (2 mL) was added into a stirred solution of 1 (2 mmol)
at -20 °C, and the reaction mixture was stirred for 5 min at
the same temperature. A solution of saturated K2CO3 (10 mL)
was added and stirred for an additional 15 min (25 °C). The
1H NMR (CDCl3): δ 0.45 (s, 3H), 0.85 (s, 6H), 0.97 (s, 3H),
4.68 (s, 1H), 4.84 (s, 1H). 13C NMR (CDCl3): δ 81.1, 83.3.
2,2-D i m e t h y l-1,3-b i s (4-m e t h o x y p h e n y l)-1,3-p r o -
p a n ed iol, 12c/13c.8 Yield: 0.145 g, 79% (based on starting
material recovery of 0.131 g, syn/ anti ) 85:15). IR (thin
film): 3340, 1615 cm-1. 1H NMR (CDCl3): δ 0.4 (s, 3H), 0.8 (s,
6H), 0.9 (s, 3H), 4.60 (s, 1H), 4.65 (s, 1H).
(23) (a) Huckin, S. N.; Weiler, L. Can. J . Chem. 1974, 52, 2157. (b)
Mukaiyama, T. Org. React. 1982, 28, 203. (c) Evans, D. A.; Chapman,
K. T.; Carreira, E. M. J . Am. Chem. Soc. 1988, 110, 3560.
(24) Hasegawa, E.; Ishiyama, K.; Horaguchi, T.; Shimizu, T. J . Org.
Chem. 1991, 56, 1631.
(25) Gaudemar-Bardone, F.; Gaudemar, M. J . Organomet. Chem.
1976, 104, 281.
(26) Emerson, W. S. J . Org. Chem. 1945, 10, 464.
(27) Fauve, A.; Veschambre, H. Biocatalysis 1990, 3(1-2), 95.
(28) Choudhary, A.; Baumstark, A. L. Synthesis 1989, 688.
(29) Fuson, R. C.; Walker, J . T. Organic Syntheses; Wiley: New
York, 1943; Collect. Vol. II, p 169.
Ack n ow led gm en t. We are grateful to the Depart-
ment of Science and Technology, New Delhi, for finan-
cial support. One of the authors (K.S.R) thanks the
Management of IDL Chemicals Ltd. and Dr. G. D.
Prasad, Chief Executive, INBRI division, for sponsor-
ship to the Ph.D. program.
J O9902906