Effect of water on Keck's catalytic asymmetric allylations of aldehydes

Article abstract of DOI:10.1055/s-2005-865202

The complex generated from BINOL, Ti(i-PrO)₄, and unactivated or a large amount of activated 4 ? MS in toluene is very effective in catalytic allylations of aldehydes using allyltributyltin. Allylations with 2.5 mol% of the catalyst provide hom

Full text of DOI:10.1055/s-2005-865202

LETTER
1109
Effect of Water on Keck’s Catalytic Asymmetric Allylations of Aldehydes
E
M
ffectof
W
ater on
K
ec
i
k’s
C
a
c
talytic
A
sy
h
A
lly
i
lations
o
of
A
ldehyde
s
Kurosu,* Miguel Lorca
Department of Chemistry and Biochemistry, The Florida State University, Tallahassee, FL 32306, USA
E-mail: mkurosu@fas.harvard.edu
Received 5 January 2005
2
3 °C.6b Brückner observed large deviations of yield and
Abstract: The complex generated from BINOL, Ti(i-PrO) , and
4
selectivity from the reported results by Keck, and devel-
oped a reliable procedure for allylstannation reactions in
which the allylation of hydrocinnamaldehyde using the
unactivated or a large amount of activated 4 Å MS in toluene is very
effective in catalytic allylations of aldehydes using allyltributyltin.
Allylations with 2.5 mol% of the catalyst provide homoallylic alco-
hols with greater than 95% ee. Very high syn-selective allylations catalyst generated from a 2:1 mixture of (R)-BINOL and
of protected b-hydroxyaldehydes are achieved with 5 mol% of the Ti(EtO) in the absence of MS in CH Cl afforded (S)-1-
4
2
2
BINOL/Ti(i-PrO) complex.
4
phenylhex-5-en-3-ol in 72% yield with 97.6% ee after 12
Key words: catalytic asymmetric allylation, 4 Å molecular sieves, days at –40 °C. Although Brückner’s conditions provide
9
BINOL, Ti(i-PrO) , allyltributyltin
4
homoallylic alcohols with excellent enantiomeric excess
the method needed to be further developed, because: (1)
2
0 mol% of the catalyst is required (with respect to
The additions of the acetate unit to aldehydes plays an im- BINOL); (2) the reactions require very long reaction times
portant role in the syntheses of most natural products of at controlled temperatures; and (3) no generalization has
1
polyketide origin. In a number of total syntheses of such been possible for catalytic asymmetric allylation reactions
molecules asymmetric allylations of aldehydes are often of chiral aldehydes. We now wish to report a very practi-
the start in constructing 1,3-polyol units. The asymmetric cal catalytic asymmetric allylation of aldehydes with the
allylations via stoichiometric amount of chiral allyl- catalyst generated from a 2:1 mixture of BINOL and Ti(i-
2
3
dialkylboranes and allyldialkoxylboranes have been PrO) (Keck’s conditions) in the presence of unactivated
4
4
widely utilized. Although impressive advances have or a large amount of activated 4 Å MS, and its application
been achieved in Lewis acid and Lewis base-catalyzed to the syntheses of syn-1,3-polyol units.
catalytic asymmetric allylation of aromatic and reactive
aldehydes, few procedures can be applied to the synthesis
of large quantities of optically active homoallylic alcohols
from various types of aldehydes. Among the catalytic
asymmetric allylation reactions developed so far, the cat-
A 1:1 mixture of BINOL and Ti(i-PrO) in strictly anhy-
4
5
drous CH Cl2 forms the BINOL/Ti(i-PrO)2 complex
2
1
10
which can be characterized by H NMR spectroscopy;
however, this complex did not catalyze allylstannations of
aldehydes. We observed that addition of unactivated 4 Å
alysts prepared from BINOL)/Ti(i-PrO) (Keck’s condi-
11
4
MS to a 2:1 mixture of BINOL and Ti(i-PrO) was very
4
6
7
8
tions), BINOL /TiCl (i-PrO) , and BINOL/Zr species
2
2
effective in the formation of an active catalyst; the allyl-
stannation of hydrocinnamaldehyde using 10 mol% of the
catalyst generated from a 2:1 mixture of (S)-BINOL and
using allyltributyltin would be applicable to a variety of
aldehydes including chiral aldehydes. The active catalysts
for allylstannations of aldehydes can be generated repro-
ducibly by mixing a 1:1 mixture of BINOL and Zr species
Ti(i-PrO) in the presence of unactivated 4 Å MS (50 mg
4
of unactivated 4 Å MS against 200 mg of BINOL) in
8
c
in the presence of 4 Å molecular sieves (MS). However,
CH Cl afforded (R)-1-phenylhex-5-en-3-ol in 95% yield
2
2
in our hands a 1:1 mixture of BINOL and Ti(i-PrO) did
12
4
with 97.8% ee after 1.5 hours at –15 °C. In our studies
on the structure elucidation of the BINOL-group IVB
transition metal complexes by Fourier transform ion cy-
not form an effective complex that catalyzed allylstanna-
tions of aldehydes in a catalytic manner with a useful level
of enantioselectivity. Keck originally reported that a 1:1
13
clotron resonance (FT-ICR) mass spectroscopy, a 2:1
mixture of BINOL and Ti(i-PrO) in the presence of 4 Å
4
mixture of BINOL and Ti(i-PrO)4 in CH Cl in the
2
2
MS under reflux in CH Cl or a 2:1 mixture of BINOL and
2
2
presence of unactivated 4 Å MS formed a large cluster
which contains multiple Ti atoms (calculated
Ti(i-PrO) in the presence of 4 Å MS and a catalytic
4
6
a
amount of TfOH in CH Cl afforded effective catalysts.
1
2
2
mass = 1819.0445). H NMR spectral analyses of the
Later, Keck modified the procedures in which allylstanna-
tions of the aromatic and aliphatic aldehydes via 20 mol%
of the complex generated from a 2:1 mixture of BINOL
and Ti(i-PrO)4 in the absence of MS afforded the
corresponding homoallylic alcohols in 89–96% ee at 0–
complex revealed that a mixture of an uncharacterizable
BINOL/Ti complex and BINOLs exists in CD Cl ; how-
2
2
ever, hydroxyl groups of unclustered BINOLs were shift-
14
ed from 5.05 ppm to 5.12 ppm. The low field change in
chemical shift observed for BINOL-OHs indicates that
unclustered BINOLs coordinate with the BINOL/Ti com-
plex. Ti(i-PrO) is known to form Ti-oxo species such as
4
SYNLETT 2005, No. 7, pp 1109–1112
Advanced online publication: 14.04.2005
DOI: 10.1055/s-2005-865202; Art ID: S00205ST
0
2.
0
5.
2
0
0
5
[
Ti O ](OR) , [Ti O ](OR) , and [Ti O ](OR) with
7 4 20 8 6 20 12 16 16
15
trace amounts of water through Ti(i-PrO) (OH). On the
3
©
Georg Thieme Verlag Stuttgart · New York

1
110
M. Kurosu, M. Lorca
LETTER
basis of the irreproducibility of the formation of an active plied the optimized conditions to structurally diverse
catalyst in strictly anhydrous CH Cl and by analyses of aldehydes and representative results are summarized in
2
1
2
an active catalyst via FT-ICR and H NMR spectroscopy, Table 1. In most cases the enantioselectivities of the prod-
it was concluded that trace amounts of water contaminat- ucts were remarkably high; allylations of the achiral alde-
ing the reaction mixture were responsible for the forma- hydes were complete within 36 hours and the isolated
tion of an active catalyst. In active catalyst formation products exhibited greater than 95% ee (entries 1–5). The
unactivated 4 Å MS were efficient as a water donor allylation of the alkynal gave rise to the propargyl alcohol
source. Interestingly, an active catalyst could also be gen- with satisfactory selectivity (entry 6); asymmetric allyla-
1
6
erated with a large amount of activated 4 Å MS (more tions of alkynals that are controlled via the cyclic transi-
than 200 mg of activated 4 Å MS against 200 mg of tion state usually result in unsatisfactory selectivities (75–
1
7
BINOL). We observed pronounced solvent effect; when 85% ee). Thus, the catalytic asymmetric allylation reac-
the reaction was carried out in toluene, the allylstannation tions described here can be utilized for the syntheses of
of hydrocinnamaldehyde using 2.5 mol% catalyst gener- relatively large amounts of optically active homoallylic
ated in the presence of activated 4 Å MS afforded (R)-1- alcohols; we have demonstrated allylation of the alde-
phenylhex-5-en-3-ol in 90% yield with 97.8% ee after 36 hydes on a 10 g scale (Table 1, entries 1 and 2), however,
hours at –15 °C. On the other hand, the same reaction in theses conditions were not applicable to aromatic alde-
CH Cl required 5 mol% catalyst to attain the same con- hydes and cinnamaldehyde (Table 1, entries 7–9).
2
2
version yield with comparable selectivity. We have ap-
RO
OAc
RO
OAc
1
) 5 mol%
S)-BINOL-Ti(OPr)4
Å MS, –15 °C
SnBu3
i
C H
7 15
C H
(
7
15
4
2a R = H
3a R = H
5)
5)
MPMO
O
2b R = MTPA
3b R = MTPA
1
2.8
C7H15
37.2
2
) Ac2O, py
3) separation
) DDQ
(
±)-1
RO
OAc
RO
OAc
4
C7H15
C7H15
4
a R = H
5a R = H
5)
4
b R = MTPA
50
0
Scheme 1 Catalytic allylstannation of (±)-1
Table 1 Catalytic Asymmetric Allylstannations of Aldehydesa
i
(
S)-BINOL-Ti(OPr)4
O
OH
4
Å MS (H2O)
SnBu3
+
R
R
toluene
–15 °C
Entry
Aldehyde (R)
PhCH CH
Catalyst (mol%)
Time (h)
36
Yield (%)
ee (%)
97.8b
95.0c
95.0b
95.5b
97.5b
90.0c
95.0b
–
1
2
3
4
5
6
7
8
2.5
2.5
2.5
2.5
2.5
2.5
10
90
85
75
90
93
85
30
10
15
2
2
C H
36
8
17
TBSOCH CH
36
2
2
BnOCH CH
36
2
2
TBDPSOCH (CH) CH
2
36
2
3
C H C≡C
24
5
11
Ph
36
p-MeOPh
trans-PhCH=CH
All reactions were carried out at 2.0 M concentration.
10
36
9
10
36
–
a
b
c
Determined by the HPLC analysis on a Chiralcel OD column.
1
Determined by H NMR spectroscopic analysis of its Mosher ester.
Synlett 2005, No. 7, 1109–1112 © Thieme Stuttgart · New York

LETTER
Effect of Water on Keck’s Catalytic Asymmetric Allylations of Aldehydes
1111
Although catalytic asymmetric allylations through acyclic system can be utilized for the syntheses of anti-1,3-diol
transition states would be useful for chiral aldehydes such units, on the other hand, the BINOL-Ti system furnishes
as b-hydroxyaldehydes, few such applications were found high syn-1,3-diol products.
1
8
in the literature. In addition, the diastereoselectivities of
allylated products seem to be significantly influenced by
the protecting groups used. As described above a 2:1 mix-
In conclusion, allylstannations of aldehydes can be
achieved with low catalytic loading of the BINOL/Ti
complex which is effectively generated from a 2:1 mix-
ture of BINOL and Ti(i-PrO) in the presence of unacti-
4
ture of BINOL and Ti(i-PrO) in the presence of unacti-
4
vated 4 Å MS formed a rather large catalyst which might
interact with the functional groups at the b-position of al-
dehydes. To investigate how the BINOL/Ti catalyst ig-
nores the b-chiral center of aldehydes, we first conducted
an allylation reaction of a racemic b-hydroxyaldehyde
possessing a MPM protecting group, (±)-1. As illustrated
in Scheme 1, the separation of diastereomers of the ace-
tates 2a and a mixture of 3a and 4a followed by analyses
of their Mosher’s esters revealed that catalytic allylation
of (±)-1 afforded 37.2:12.8 ratio of anti- and syn-products
which originated from (S)-3-(4-methoxybenzyloxy) deca-
nal [(S)-1]. On the other hand, under these conditions (R)-
vated or a large amount of activated 4 Å MS, which act as
a controllable water donor source. The allylation reactions
of achiral aldehydes proceeded within 36 hours at –15 °C
and the enantiomeric excess of the homoallylic alcohols
are greater than 95%. The catalytic asymmetric allylstan-
nations via the BINOL-Ti(i-PrO) system are very useful
4
for the syntheses of syn-1,3-polyol units.
(
R)-Undec-1-en-4-ol; Typical Procedure (Table 1, entry 2)
2
2
To a stirred mixture of (S)-BINOL (560 mg, 1.96 mmol) and
activated 4 Å MS (1.12 g) in anhyd toluene (150 mL) was added
1
9
1
was converted to the syn-product exclusively. The syn-
Ti(i-PrO) (278 mg, 0.98 mmol). The reaction mixture was stirred
4
selective catalytic asymmetric allylation observed for a for 2.5 h at r.t. At –15 °C allyltributyltin (39 g, 118 mmol) and oc-
racemic aldehyde was confirmed by the catalytic tanal (10.0 g, 78.4 mmol) were added. After 36 h at –15 °C, a 2:1
mixture of powdered CsF/CsOH (20 g) and silica gel (40 g) were
asymmetric allylations of several optically pure (R)-3-hy-
2
3
droxylaldehyde derivatives, 6a–c and 7 (Scheme 2).20
added. The reaction mixture was stirred for an additional 2 h and
all volatiles were evaporated in vacuo. Purification by silica gel
chromatography (hexanes–EtOAc–CH Cl , 20:1:2 to 10:1:2)
2
2
1
1
R O
O
R O
OH
27
5
mol%
afforded (R)-undec-1-en-4-ol (11.4 g, 85%), [a]D +6.9 (c 1.0,
i
(
S)-BINOL-Ti(OPr)4
CHCl3).
R
R
6a–c
4 Å MS
SnBu3
8a–c
+
toluene
–15 °C
Acknowledgment
O
O
O
O
O
OH
This work was supported by The Florida State University. Dr. Alan
Marshall and Mr. Robert Bossio are gratefully acknowledged for
high-resolution mass spectral measurements. We thank Dr. Albet E.
Stiegman for a useful discussion on the Ti oxides.
R
R
7
9
products
MPMPO
C7H15
OH
BnO
OH
MOMO
OH
References
C7H15
C7H15
8
a
8b
8c
85% (93.4% de)
(1) (a) Heathcock, C. H. In Asymmetric Synthesis, Vol. 3;
Morison, J. D., Ed.; Academic Press: New York, 1984, 111.
9
0% (97.0% de)
89% (96.5% de)
(
b) Evans, D. A.; Nelson, J. V.; Taber, T. R. Top.
Stereochem. 1982, 13, 1. (c) Mukaiyama, T. Org. React.
N.Y.) 1982, 28, 203.
O
O
OH
(
TIPSO
9
(2) Brown, H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewiez, M.;
85% (92.0% de)
Racherla, U. S. J. Am. Chem. Soc. 1990, 112, 2389.
(
3) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Park, J.-C. J.
Org. Chem. 1990, 55, 4109.
Scheme 2 Catalytic asymmetric allylstannations of chiral
aldehydes
(4) For other useful chiral allylating reagents see: (a) Riediker,
M.; Duthaler, R. O. Angew. Chem., Int. Ed. Engl. 1989, 28,
4
94. (b) Hafner, A.; Duthaler, R. O.; Marti, R.; Rihs, J.;
In general due to the high oxophilicity of Lewis acids, al-
Rothe-Streit, P.; Schwarzenbach, F. J. Am. Chem. Soc. 1992,
lylstannations of chiral b-hydroxyaldehydes results in fa-
9
9
2, 807. (c) Duthaler, R. O.; Hafner, A. Chem. Rev. 1992,
2, 807; and references cited therein.
2
1
vor of chelation-controlled products (anti-products). We
reported that BINOL-Zr(t-BuO) mediated anti-selective
4
(5) (a) Furuta, K.; Miwa, Y.; Iwanaga, K.; Yamamoto, H. J. Am.
Chem. Soc. 1988, 54, 1481. (b) Furuta, K.; Mouri, M.;
Yamamoto, H. Synlett 1991, 561. (c) Marshall, J. A.; Tang,
Y. Synlett 1992, 653. (d) Ishihara, K.; Mouri, M.; Gao, Q.;
Maruyama, T.; Furuta, K.; Yamamoto, H. J. Am. Chem. Soc.
catalytic asymmetric allylstannations of b-hydroxyalde-
hydes protected with a variety of protecting groups. The
diastereoselectivities observed in the allylation reactions
of a series of chiral aldehydes using the BINOL/Zr com-
plex clearly indicates that it is difficult to attain high syn-
1
993, 115, 11490. (e) Denmark, S. E.; Coe, D. M.; Pratt, N.
E.; Griedel, B. D. J. Org. Chem. 1994, 59, 6161.
f) Kobayashi, S.; Nishio, K. J. Am. Chem. Soc. 1995, 117,
392. (g) Iseki, K.; Mizuno, S.; Kuroki, Y.; Kobayashi, Y.
8
c
selectivity. Therefore, BINOL/Ti mediated syn-selec-
tive catalytic allylstannations of b-alkoxyaldehydes is
complementary to the BINOL/Zr system; the BINOL-Zr
(
6
Tetrahedron 1999, 55, 977. (h) Nakajima, M.; Saito, M.;
Synlett 2005, No. 7, 1109–1112 © Thieme Stuttgart · New York

1
112
M. Kurosu, M. Lorca
LETTER
Shiro, M.; Hashimoto, S. J. Am. Chem. Soc. 1998, 120, 641.
(15) (a) Jones, A. C.; Leedham, T. J.; Wright, P. J.; Crosbie, M.
J.; Fleeting, K. A.; Otway, D. J.; O’Brien, P.; Pemble, M. E.
J. Mater. Chem. 1998, 8, 1773. (b) Hubert-Pfalzgraf, L. G.
J. Mater. Chem. 2004, 14, 3113; and references cited therein.
(16) Powdered 4 Å MS (available from Aldrich) were activated
at 200 °C under high vacuum for 12 h, it is believed that
water still remained inside activated 4 Å MS. Activated 3 Å
and 5 Å MS were less effective in the formation of an active
catalyst than 4 Å MS.
(
i) Chataigner, I.; Piarulli, U.; Gennari, C. Tetrahedron Lett.
999, 120, 6419. (j) Hanawa, H.; Kii, S.; Asao, N.;
Maruoka, K. Tetrahedron Lett. 2000, 41, 5543.
k) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763; and
1
(
references cited therein. (l) For catalytic asymmetric
Barbier-type reactions see: Kurosu, M.; Lin, M.-H.; Kishi,
Y. J. Am. Chem. Soc. 2004, 126, 12248; and references cited
therein.
(
6) (a) Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem.
Soc. 1993, 115, 8268. (b) Keck, G. E.; Geraci, L. S.
Tetrahedron Lett. 1993, 34, 7827. (c) Yu, C.-M.; Choi, H.-
S.; Yoon, S.-K.; Jung, W.-H. Synlett 1997, 889.
7) Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.;
Umani-Ronchi, A. J. Am. Chem. Soc. 1993, 115, 7001.
8) (a) Bedeschi, P.; Casolari, S.; Costa, A. L.; Tagliavini, E.;
Umani-Ronchi, A. Tetrahedron Lett. 1995, 36, 7897.
(17) The allylstannation of hydrocinnamaldehyde using the
complex generated in the presence of 50–100 mg of
activated 4 Å MS [against 200 mg of (S)-BINOL] afforded
(R)-1-phenylhex-5-en-3-ol in 70–80% yields with 60–70%
ee. The same scale experiment using the complex generated
with 150 mg of activated 4 Å MS afforded the product in
82% yield with 85% ee.
(18) (a) Molinski, T. F.; Searle, P. A. J. Am. Chem. Soc. 1996,
118, 9422. (b) Roush, W. R.; Champoux, J.; Peterson, B. C.
Tetrahedron Lett. 1996, 37, 8989.
(19) We believe that the procedures described here are an
expeditious method for the analysis of selectivity of chiral
reagent against chiral substrates. For an analogous concept
for resolutions of chiral racemic ketons via a chiral reducing
reagent see: Kurosu, M.; Kishi, Y. J. Org. Chem. 1998, 63,
6100.
(
(
(
b) Casolari, S.; Cozzi, G. C.; Orioli, P.; Tagliavini, E.;
Umani-Ronchi, A. Chem. Commun. 1997, 2123.
c) Kurosu, M.; Lorca, M. Tetrahedron Lett. 2002, 43, 1765.
9) Weigand, S.; Brückner, R. Chem.–Eur. J. 1996, 2, 1077.
(
(
(
(
(
10) Terada, M.; Matsumoto, Y.; Nakamura, Y.; Mikami, K.
Inorg. Chim. Acta 1999, 296, 267.
11) Powdered 4 Å MS (available from Aldrich) were used for
this study.
12) In our hands the same reaction under the reported conditions
by Keck6b afforded (R)-1-phenylhex-5-en-3-ol in 50% yield
with 75.0% ee. For an analogous observation see reference
(20) Stereochemistry of the skipped-triols were confirmed by
using Kishi’s universal NMR databases see: (a) Kobayashi,
Y.; Tan, C.-H.; Kishi, Y. Angew. Chem. Int. Ed. 2000, 39,
4279. (b) Higashibayashi, S.; Kishi, Y. J. Am. Chem. Soc.
2003, 125, 1437; and references cited therein.
9.
(13) Senko, M. W.; Hendrickson, C. L.; Emmett, M. R.; Shi, S.
D. H.; Marshall, A. J. Am. Soc. Mass Spectrom. 1997, 8, 970.
(21) (a) Nagaoka, H.; Kishi, Y. Tetrahedron 1981, 37, 3873.
(b) Keck, G. E.; Abbott, D. E. Tetrahedron Lett. 1984, 25,
1883.
1
(
14) H NMR spectra (300 MHz, CD Cl ) of (S)-BINOL and the
2
2
active BINOL/Ti complex.
(
22) (S)-BINOL was purchased from Kankyo Kagaku Center Co.
Ltd.
(
23) A mixture of powdered CsF/CsOH (2:1) and silica gel was
effective to remove both Sn and Ti species see: Edelson, B.
J.; Stoltz, B. M.; Corey, E. J. Tetrahedron Lett. 1999, 40,
6729.
Figure 1
Synlett 2005, No. 7, 1109–1112 © Thieme Stuttgart · New York