Asymmetric conjugate addition of alkynylboronates to enones [11]

Full text of DOI:10.1021/ja992922b

1822
J. Am. Chem. Soc. 2000, 122, 1822-1823
Asymmetric Conjugate Addition of Alkynylboronates
to Enones
Scheme 1
J. Michael Chong,* Lixin Shen, and Nicholas J. Taylor
Guelph-Waterloo Centre for Graduate Work in
Chemistry and Biochemistry, Department of Chemistry
UniVersity of Waterloo, Waterloo, Ontario, Canada N2L 3G1
Scheme 2
ReceiVed August 12, 1999
Michael addition of organometallics, particularly organocop-
1
2
pers and organozincs, to R,â-unsaturated carbonyl compounds
is a well-established method for the formation of carbon-carbon
bonds. Over the past two decades, asymmetric versions of these
reactions, particularly with copper reagents, have been developed
which can be highly selective.3 However, one important limita-
tion of organocopper reagents is that they do not efficiently
,4
5
transfer alkynyl groups to organic substrates (Scheme 1). Since
alkynyl groups may be readily manipulated into many other
functionalities,6 we were interested in filling this void by
developing reactions which could stereoselectively add alkynyl
groups in a Michael fashion to R,â-unsaturated carbonyl com-
pounds. We now report the first examples of enantioselective
conjugate additions of alkynyl groups to enones.7
pared by reaction of an alkynyllithium with a borate followed by
treatment of the resulting adduct with HCl or BF
3
2
‚OEt . Since it
Conjugate alkynyl group transfer using achiral reagents had
been achieved with alkynylboron8 and aluminum9 reagents.
is known that transesterification of B-1-alkynylboronates is not
an effective reaction,1 the most straightforward route to boronates
4a
However, it appears that no asymmetric versions of these reactions
have been reported.
2
would be to add alkynyllithiums to a mixed borate such as
14
binaphthyl isopropyl borate (1). However, we were unable to
We reasoned that an alkynylboronate derivative of a chiral diol
prepare compounds such as 1.1
5,16
might be an asymmetric conjugate alkynylation reagent.1
0-12
1,1′-
Eventually it was found that reaction of binaphthol (3a) with
lithium B-1-octynyltriisopropylborate (4a) (with removal of
i-PrOH) provided borate 5a (Scheme 3).17 As expected, this com-
plex was unreactive toward enones. However, it was anticipated
Bi-2-naphthol has been used as a very effective chiral auxiliary
in many asymmetric transformations13 so we directed our initial
efforts to prepare reagents of general structure 2 (Scheme 2). It
has previously been shown14 that alkynylboronates may be pre-
that, in analogy with previous work,1 addition of acid (e.g. HCl
4a
(
1) Lipshutz, B. H.; Sengupta, S. Org. React. 1992, 41, 135-631.
18
or BF
Indeed, treatment of 5a and chalcone in CH
ature with HCl or BF ‚OEt provided the expected 1,4-addition
product cleanly in high yield. The observed enantioselectivity
31% ee) was disappointingly low but showed that enantioselec-
3
‚OEt
2
) would generate the reactive trivalent boronate 2a.
(
2) Jansen, J. F. G. A.; Feringa, B. L. J. Chem. Soc., Chem. Commun. 1989,
2
Cl
2
at room temper-
7
41-742.
(
3) Reviews: (a) Rossiter, B. E.; Swingle, N. M. Chem. ReV. 1992, 92,
3
2
7
71-806. (b) Krause, N. Angew. Chem., Int. Ed. Engl. 1998, 37, 283-285.
(
4) Organozincs: Alexakis, A.; Vastra, J.; Burton, J.; Benhaim, C.;
(
Mangeney, P. Tetrahedron Lett. 1998, 39, 7869-7872 and references therein.
(
5) It has recently been shown that alkynylcuprates will add to enones in
tive conjugate alkynylation using this type of chemistry is possible.
the presence of trialkylsilyl triflates or TMSI: (a) Kim, S.; Park, J. H.; Jon,
S. Y. Bull. Korean Chem. Soc. 1995, 16, 783-786. (b) Eriksson, M.; Iliefski,
T.; Nilsson, M.; Olsson, T. J. Org. Chem. 1997, 62, 182-187.
19
It was gratifying to find that when 3,3′-diphenylbinaphthol 3b
was used in place of the parent binaphthol 3a, addition to chalcone
was considerably more selective (Table 1). In general, reactions
gave high yields of 1,4-addition products with no detectable side-
products. In all cases, reactions using the 3,3′-diphenylbinaphthol
reagent were much more selective than those with the unsubsti-
tuted binaphthol. In fact, with aryl groups in the â-position,
enantioselectivities were uniformly high, ranging from 85 to
(
6) Hudrlik, P. F.; Hudrlik, A. M. Applications of Acetylenes in Organic
Synthesis. In The Chemistry of the Carbon-Carbon Triple Bond; Patai, S.,
Ed.; John Wiley and Sons: Chichester, 1978; Part 1, pp 199-273.
(
7) An account of preliminary work was presented at the 81st Canadian
Society for Chemistry Conference and Exhibition, Whistler, BC, Canada, May
3
1-June 4, 1998, abstract No. 297.
8) (a) Sinclair, J. A.; Molander, G. A.; Brown, H. C. J. Am. Chem. Soc.
977, 99, 954-956. (b) Fujishima, H.; Takada, E.; Hara, S.; Suzuki, A. Chem.
(
1
Lett. 1992, 695-698.
(
9) (a) Hooz, J.; Layton, R. B. Can. J. Chem. 1973, 51, 2098-2101. (b)
(15) It has been suggested that reaction of binaphthol with triphenylborate
generates the “expected” mixed borate but it has not been isolated or
spectrocopically characterized: refs 13b and 13c.
Schwartz, J.; Carr, D. B.; Hansen, R. T.; Dayrit, F. M. J. Org. Chem. 1980,
4
5
5, 3053-3061. (c) Yoshino, T.; Okamoto, S.; Sato, F. J. Org. Chem. 1991,
6, 3205-3207.
(
(16) Many attempts to prepare mixed alkyl binaphthyl borates gave a boron
bridged trimer of binaphthol: Kaufmann, D.; Boese, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 545-546.
10) (a) Matteson, D. S.; Man, H.-W.; Ho, O. C. J. Am. Chem. Soc. 1996,
1
18, 4560-4566. (b) Roush, W. R. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 2, pp
(17) Borate 4a was easily prepared by addition of 1-octynyllithium to
1
-79.
(
triisopropyl borate. The formation of 5a could be assayed by the position of
1
11) Asymmetric conjugate addition of aryl- and alkenylboronic acids has
the isopropyl methine signal in the H NMR (CDCl
3 6
/DMSO-d ) spectra: 4a,
been described: Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.; Miyaura,
δ 3.98; 5a, δ 4.41.
N. J. Am. Chem. Soc. 1998, 120, 5579-5580.
(18) Attempts to isolate boronate 2a were only partially successful.
(
12) Alkynylboranes have been used in asymmetric alkynylations of
Treatment of borate 5a with BF
3
‚OEt followed by removal of volatiles in
2
1 13
aldehydes: Corey, E. J.; Cimprich, K. A. J. Am. Chem. Soc. 1994, 116, 3151.
vacuo gave a white solid which exhibited H and C NMR spectra consistent
with 2a but containing signals for other related compounds as well. The
intensities of these other signals increased with time, suggesting slow
decomposition of boronate 2a.
(
13) (a) Rosini, S.; Franzini, L.; Rafaelli, A.; Salvadori, P. Synthesis 1992,
5
3
03-517. (b) Hattori, K.; Yamamoto, H. J. Org. Chem. 1992, 57, 3264-
265. (c) Ishihara, K.; Miyata, M.; Hattori, K.; Tada, T.; Yamamoto, H. J.
Am. Chem. Soc. 1994, 116, 10520-10524. (d) Shibasaki, M.; Sasai, H.; Arai,
(19) Addition of substituents in the 3,3′-positions of binaphthol can
dramatically increase enantioselectivities: (a) Kelly, T. R.; Whiting, A.;
Chandrakumar, N. S. J. Am. Chem. Soc. 1986, 108, 3510-3512. (b) Maruoka,
K.; Itoh, T.; Shirasaka, T.; Yamamoto, H. J. Am. Chem. Soc. 1988, 110, 310-
312. (c) Ishihara, K.; Kurihara, H.; Matsumoto, M.; Yamamoto, H. J. Am.
Chem. Soc. 1998, 120, 6920-6930.
T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1236-1256.
2
(14) Unsymmetric borates of general structure (R′O) BOR have been used
to prepare alkynylboronates: (a) Brown, H. C.; Bhat, N. G.; Srebnik, M.
Tetrahedron Lett. 1988, 29, 2631-2634. (b) Deloux, L.; Srebnik, M. J. Org.
Chem. 1994, 59, 6871-6873.
1
0.1021/ja992922b CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/12/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 8, 2000 1823
Scheme 3
Figure 1. Cyclic 6-membered chair-transition states.
surprising to find that 2b did not react with 2-cyclohexenone.
Similarly, no reaction was observed with a â,â-disubstituted enone
(
dypnone). Reactions of Z enones gave essentially the same
20
selectivities as their E counterparts.
The adducts 7i and 8i were prepared particularly to shed some
light on the absolute configuration of the addition products. Using
R binaphthol 3b produced alkynyl ketones 7i and 8i with R
stereochemistry (X-ray). This stereochemistry is the stereochem-
istry predicted based on a cyclic six-membered transition state
similar to that proposed by Brown for additions of alkynyl 9-BBN
Table 1. aEnantioselective Conjugate Addition of Alkynyl Groups
to Enones
8a
reagents to enones and also by Noyori for the asymmetric
2
1
reduction of alkyl aryl ketones with BINAL-H (Figure 1). This
model is also consistent with the enhanced selectivity observed
with 3,3′-substituents. Thus, of the two possible types (based on
the diastereotopicity of the binaphthoxy oxygens) of chair-
transition states 10 and 11, structure 10 is disfavored due to steric
interactions. With structures such as 11, there would be two
possible diastereomeric transition states with 11R favored over
11S. This model fits well with the observed dependence of
enantioselectivity on both the size and electronic nature of the
â-substituent on the enone.22
In conclusion, we have found that alkynylboronates 2 can
transfer alkynyl groups regioselectively and enantioselectively to
enones.23 These represent the first enantioselective conjugate al-
kynylations. We are currently investigating the effects of other diol
ligands on this reaction and will report these results in due course.
b
c
b
c
Acknowledgment. We thank the Natural Sciences and Engineering
Research Council of Canada (NSERC) for financial support and the
Ontario Government for an Ontario Graduate Scholarship (to L.S.).
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6
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b
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c
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2a
2a
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2b
2b
2b
2b
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7b
7c
7a
7b
7d
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7e
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8i
Supporting Information Available: Experimental details and spec-
troscopic data for the preparation of binaphthol 3b, boronates 4a, 5a,
and 5b, enones 6c-i, and adducts 7a-i, 8a, 8h, 8i, and 9h; X-ray
structural information on 7i and 8i (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
91
93
90
99
87
95
75
90
98
90
e
6h
9h
81 >98d
JA992922B
a
Reactions run at room temperature as described in ref 23. b Isolated
(20) When 2b was allowed to react with Z-6a and Z-6d, 7a and 7d were
produced in 90% and 4% ee, respectively. In both cases, the major isomer
was the same as that produced using the E enone, suggesting isomerization
to the E isomer occurred under the reaction conditions.
c
yields of chromatographed material. Determined by HPLC using a
Chiralcel OD column. Minor isomer not detected by HPLC analysis.
d
(
21) Noyori, R.; Tomino, I.; Tanimoto, Y.; Nishizawa, M. J. Am. Chem.
>
98% ee. With alkyl groups in the â-position, there was a
Soc. 1984, 106, 6709-6716.
pronounced steric effect wherein selectivities increased with the
size of the substituent. There was also an increase in selectivity
when the size of the aryl group in the â-position was increased.
Overall, it seems that alkynylboronates 2 efficiently transfer
alkynyl groups to enones; an aryl group directly attached to the
carbonyl carbon of the enone is important for high reactivity while
both the size and electronic character of the â-substituent are
important for selectivity. Best selectivities were observed with
â-substituents which have electron-rich π-systems.
(22) The absolute configurations of the other adducts in Table 1 are
unknown at this time, but it is expected that they will also be consistent with
our working model.
(
23) Representative preparative procedures follow. Borate 5b: To a cooled
(
0 °C) mixture of binaphthol 3b (0.416 mmol) and 4a (0.345 mmol) under
Ar was added THF (15 mL). The mixture was stirred at 0 °C for 1 h, then at
room temperature for 3 h. The solvent was removed and the resulting white
solid was dried in vacuo overnight to give compound 5b in quantitative yield.
Alkynylation: To a mixture of adduct 5b (0.345 mmol), an enone (0.232
mmol), and CH
2
Cl
2
(15 mL) was added BF
3
2
‚OEt (58 µL, 0.461 mmol). After
4
reaction was complete (or no further change by TLC, 1-24 h), saturated NH -
Cl (2 mL) and water (2 mL) were added to quench the reaction. Standard
aqueous workup afforded the 1,4-addition product (see Table 1 for yields)
and 3b (>95% recovery).
Since it is known that alkynyl 9-BBN reagents add only to
enones capable of achieving an s-cis conformation,8a it was not