Catalytic asymmetric prop-2-ynylation involving the use of the bifunctional synergetic reagent Et2BSPri

Article abstract of DOI:10.1039/a700540g

Efficient catalytic asymmetric prop-2-ynylation of achiral aldehydes with allenyltributylstannane promoted by a BINOL-Ti^IV complex (10 mol%) is achieved with high enantioselectivity by the use of Et₂BSPrⁱ.

Full text of DOI:10.1039/a700540g

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Catalytic asymmetric prop-2-ynylation involving the use of the bifunctional
synergetic reagent Et2BSPri
Chan-Mo Yu,* Sook-Kyung Yoon, Ha-Soon Choi and Kwangwoo Baek
Department of Chemistry, Sung Kyun Kwan University, Suwon 440-746, Korea
Efficient catalytic asymmetric prop-2-ynylation of achiral
aldehydes with allenyltributylstannane promoted by a
BINOL–TiIV complex (10 mol%) is achieved with high
enantioselectivity by the use of Et2BSPri.
added dropwise Et2BSPri (1.2 equiv.) in CH2Cl2. After 9 h at
220 °C, the reaction mixture was quenched by the addition of
saturated aqueous NaHCO3. Work up and silica gel chromatog-
raphy (SiO2, deactivated with 1% of Et3N in hexane; eluent,
hexane–EtOAc) afforded the alcohol 4 (R = CH2CH2Ph) in
86% isolated yield and 94% ee. Using these optimal conditions,
a range of experiments on the catalytic asymmetric prop-
2-ynylation of aldehydes was carried out. From Table 2 it can be
seen that asymmetric prop-2-ynylations were conducted on a
variety of aldehydes under identical conditions to furnish
alcohols 4 with excellent enantioselectivities. Reaction times
and chemical yields, as indicated in Table 2, were dependent on
the steric environment of the substrates. It is worthy of note that
the reaction also produced trace amounts of isomeric allenyl
alcohol ( < 2%) according to analysis of the 1H NMR spectra of
the crude products. A reduced dosage of chiral catalyst 5
We report here a useful catalytic method for the enantioselec-
tive synthesis of but-3-yn-1-ols from the reaction of an
allenyltin reagent with achiral aldehydes promoted by a chiral
Lewis acid together with a synergetic reagent. Among the
fundamental asymmetric reactions, allylic transfer from chiral
reagents to a carbonyl functionality, forming enantiomeric rich
homoallylic alcohols, attracts considerable attention from the
synthetic community since the resulting products serve as chiral
building blocks for multi-step syntheses.1 In spite of the
structural versatility of the prop-2-ynylic system, there have
been few reports in this area compared with the allylic system,
mainly due to a lack of reactivity and regiochemical problems.2
While a couple of chiral allenyl reagents employing chiral
auxiliaries have been developed to realize a highly enantio- and
regio-selective synthesis of but-3-yn-1-ols,3 catalytic chiral
Lewis acids have been introduced in the reaction of aldehydes
with allenylstannane.4 Nonethless, the method for catalytic
asymmetric prop-2-ynylation employing chiral Lewis acids is
not ideal, mainly due to poor catalytic ability (50–100 mol%)
and long reaction times (72–100 h). The method described
herein is successful with a variety of aldehydes in the presence
of a catalyst employing a bifunctional synergetic reagent and
affords products of high enantiomeric purity. The process
utilizes a readily available alkylthioborane as a synergetic
reagent.
Our initial studies began with hydrocinnamaldehyde 1 and
allenyltributylstannane 2.5 Treatment of 1 with 2 in the presence
of (S)-BINOL–TiIV (10 mol%) in CH2Cl2 at 220 °C for 24 h
afforded only a barely detectable amount of adduct 4. We
subsequently observed that synergetic reagents, which were
previously utilized for catalytic asymmetric allylation,6 can also
be employed for catalytic asymmetric prop-2-ynylation. After
surveying series of alkylthioboranes and alkylthiosilanes,
several key points emerged: (i) Et2BSPri was generally superior
to other reagents, including Me3SiSPri; (ii) a 1:1 mixture of the
BINOL–Ti(OPri)4† or BINOL–Zr(OPri)4‡ complexes proved to
be the most effective catalyst; (iii) the new systems exhibited a
dramatic acceleration of the reaction rate as well as significantly
increasing catalytic ability in comparison with the non-
accelerator system;4 (iv) optimal chemical yields and enantiose-
lectivities were observed with the use of CH2Cl2 as a solvent
compared to other solvents such as toluene, diethyl ether or
propionitrile. Selected results for the preliminary studies are
summarised in Table 1. Especial encouraging were entries 2 and
5; therefore, chiral catalysts BINOL–TiIV and –ZrIV with
Et2BSPri were chosen for systematic studies because they
exhibited high level of enanatioselectivity with reasonable
chemical yields.
Table 1 Selected data for preliminary investigations
(S)-BINOL–MX2
(10 mol%)
3
SnBu3
H
HO
R
H
RCHO
+
Accelerator
–20 oC, CH2Cl2
1
2
4
R = CH2CH2Ph
Entry
MX2
Accelerator
t/h
Yield (%)
Ee (%)
a
a
b
a
d
1
2
3
4
5
Ti(OPri)2
Ti(OPri)2
Ti(OPri)2
Ti(OPri)2
Control
20
9
9
9
8
Trace
86
84
57c
72
—
94
93
—
92
Et2BSPri
Et2BSPri
Me3SiSPri
Et2BSPri
Zr(OPri)2
a
b
c
BINOL–Ti(OPri)4 = 1:1. BINOL–Ti(OPri)4 = 2:1. Isolated yield
after desilylation (Bu4NF). d BINOL + Zr(OPri)4.
Table 2 Catalytic prop-2-ynylation promoted by the BINOL–TiIV com-
plexa,b
SnBu3
(S)-BINOL–TiIV
Et2BSPri
5
HO
R
H
RCHO
+
H
–20 oC, CH2Cl2
1
2
4
Entry
R
5 (mol%) t/h
Yield (%)c
Ee (%)d
1
2
3
4
5
6
7
PhCH2CH2
PhCH2CH2
C6H11
10
5
10
5
10
10
10
9
18
9
18
15
15
15
86
65
75
51
73
61
52
94
91
92
88
91
95
92
C6H11
c-C6H11
Me2CHCH2
Ph
a All reactions were run at 220 °C. b Absolute configurations were verified
by comparison of specific rotation sign with authentic and/or literature
The prop-2-ynylation reaction was performed according to
the following procedure: all reactions were carried out in the
presence of 4 Å molecular sieves to remove any trace of water.
To a solution of 1 (R = CH2CH2Ph, 1 equiv.) and 2 (1.3 equiv.
in the presence of (S)-BINOL–TiIV 5 (10 mol%) at 220 °C was
c
d
values. Yields refer to isolated and purified products. Enantiomeric
excess values were determined by preparation of (+)-MTPA ester
derivatives, analysis by 1H NMR spectroscopy (CHOR) and comparison
with authentic and racemic samples.
Chem. Commun., 1997
763

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In conclusion, the enantioselective prop-2-ynylation of
achiral aldehydes, a process of clear synthetic potential, has
been advanced to a new level of practicality and stereoselectiv-
ity as a result of the utilization of a molecular accelerator to
increase catalytic ability and reactivity. Studies are in progress
to extend this chemistry to more highly functionalised tin
reagents, including racemic allenylstannanes for kinetic resol-
utions. We believe that further studies will provide a better
understanding of this chemical phenomenon.
Generous financial support of this work by grants from the
Ministry of Education (BSRI 96-3420) and the Korea Science
and Engineering Foundation (KOSEF 94-0501-08-01-03) is
gratefully acknowledged.
resulted in diminished chemical yields, longer reaction times
and poorer stereoselectivites.
Catalytic asymmetric prop-2-ynylation promoted by the
(S)-BINOL– ZrIV‡ complex was also investigated under similar
conditions to those described above. Most of the isolated major
alcohols were contaminated with a trace of the isomeric allenyl
alcohol ( < 3%), but in the case of cyclohexanecarbaldehyde the
product ratio proved to be 93:7 as judged by 1H NMR
spectroscopic analysis of the crude products. The data sum-
marised in Table 3 allow the following points to be stated: (i) as
expected, the process using the molecular accelerator is
effective in terms of reaction time as well as chemical yield; (ii)
in general, the ZrIV complex provides modest to excellent
enantioselectivities, which are somewhat lower than those of
the TiIV complex; (iii) the enantioselectivities correlate with the
degree of steric hindrance in the substrates.
The work disclosed here is innovative mainly because of the
reinforcement of catalytic ability outlined, especially with the
less reactive allenylstannane.8 However, further extension of
the understanding of this chemistry is required in the following
areas: (i) the exact mechanism by which Et2BSPri accelerates
the catalytic process,which involves dissociation of the product
from the reaction complex and regeneration of the chiral
catalyst; (ii) the origin of isomeric allenyl alcohols is also
unclear, and may involve equilibration between allenyl- and
prop-2-ynyl-tin reagents or a- and g-orientation to tin in the
transition state.
Footnotes
† The (S)-BINOL–TiIV complex was prepared from the reaction of
(S)-BINOL with Ti(OPri)4 in the presence of activated powdered 4 Å
molecular sieves at 20 °C for 3 h (ref. 4).
‡ The (S)-BINOL–ZrIV complex was prepared from the reaction of
(S)-BINOL with Zr(OPri)4 in the presence of activated powdered 4 Å
molecular sieves at 20 °C for 2 h (ref. 7).
References
1 For comprehensive reviews, see Y. Yamamoto and N. Asao, Chem. Rev.,
1993, 93, 2207; J. A. Marshall, Chem. Rev., 1996, 96, 31; M. Santell and
J.-M. Pons, Lewis Acids and Selectivity in Organic Chemistry, CRC
Press, New York, 1996, pp. 91–184.
2 H. Yamamoto, in Comprehensive Organic Synthesis: Propargyl and
Allenyl Organometallics, ed. C. H. Heathcock, Pergamon, Oxford, 1991,
vol. 2, pp. 81–98.
Table 3 Catalytic prop-2-ynylation promoted by the BINOL-ZrIV com-
plex
3 N. Ikeda, I. Arai and H. Yamamoto, J. Am. Chem. Soc., 1986, 108, 483;
E. J. Corey, C.-M. Yu and D.-H. Lee, J. Am. Chem. Soc., 1990, 112,
878.
4 G. E. Keck, D. Krishnamurthy and X. Chen, Tetrahedron Lett., 1994, 35,
8323.
(S)-BINOL–ZrIV
10 mol %
6
SnBu3
H
HO
R
H
RCHO
+
Et2BSPri
–20 oC, CH2Cl2
5 H. Tanaka, A. K. M. Abdul Hai, H. Ogawa and S. Torri, Synlett, 1993,
835.
1
2
4
6 C.-M. Yu, H.-S. Choi, W.-H. Jung and S.-S. Lee, Tetrahedron Lett.,
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7 P. Bedeshi, S. Casolari, A. L. Costa, E. Tagliavini and A. Umani-Ronchi,
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Entry
R
t/h
Yield (%)
72
71
67
65
44
Ee (%)
1
2
3
4
5
PhCH2CH2
C6H11
c-C6H11
Me2CHCH2
Ph
9
92
87
68
91
71
9
15
15
15
8 J. A. Marshall, J. A. Jablonowski and G. S. Welmaker, J. Org. Chem.,
1996, 61, 2904 and references cited therein.
Received in Cambridge, UK, 23rd January 1997; Com.
7/00540G
a All conditions were identical with those of Table 2.
764
Chem. Commun., 1997