Potassium alkenyl- and aryltrifluoroborates: Stable and efficient agents for rhodium-catalyzed addition to aldehydes and enones

Article abstract of DOI:10.1021/ol9910767

(matrix presented). Potassium alkenyl- and aryltrifluoroborates undergo addition to enones and aldehydes in the presence of Rh(I) catalysts to give β-functionalized ketones and allylic/benzylic alcohols, respectively. Reaction proceeds more rapidly than with the corresponding boronic acids, and the choice of phosphine ligand does not signifcantly influence the overall efficiency of addition.

Full text of DOI:10.1021/ol9910767

ORGANIC
LETTERS
1999
Vol. 1, No. 10
1683-1686
Potassium Alkenyl- and
Aryltrifluoroborates: Stable and Efficient
Agents for Rhodium-Catalyzed Addition
to Aldehydes and Enones
Robert A. Batey,* Avinash N. Thadani, and David V. Smil
Department of Chemistry, Lash Miller Chemical Laboratories, UniVersity of Toronto,
Toronto, Ontario, Canada, M5S 3H6
rbatey@chem.utoronto.ca
Received September 22, 1999
ABSTRACT
Potassium alkenyl- and aryltrifluoroborates undergo addition to enones and aldehydes in the presence of Rh(I) catalysts to give â-functionalized
ketones and allylic/benzylic alcohols, respectively. Reaction proceeds more rapidly than with the corresponding boronic acids, and the choice
of phosphine ligand does not signifcantly influence the overall efficiency of addition.
The use of organometallics as nucleophilic reagents is
arguably the most important method for the formation of
C-C bonds.1 Two of the most widely used reactions are
additions to carbonyl groups and conjugate additions to R,â-
unsaturated carbonyls by organolithium/Grignard and organo-
copper/zinc reagents, respectively. A variety of other organo-
metallic reagents have also been employed for these trans-
formations. Recently, Miyaura and co-workers extended the
scope of reagents to include organoboron compounds,
demonstrating the rhodium(I)-catalyzed addition of aryl- and
alkenylboronic acids to aldehydes2 and enones.3 A catalytic
asymmetric 1,4-addition to enones has also been reported
by the same authors.3b A major advantage over existing
methods is the relative stability of boronic acids to air and
moisture. As part of an ongoing program in organoboron
research,4 we have also been developing nucleophilic addition
reactions of organoboron compounds, including the use of
stable potassium allyl- and crotyltrifluoroborate salts as
efficient reagents for allylation and crotylation of aldehydes
and pyruvates,4a and the addition of alkenyl- and aryl-
boronates to N-acyliminium ions.4b We now report the Rh(I)-
catalyzed addition of air- and moisture-stable potassium
alkenyl- and aryltrifluoroborates 1 to enones and aldehydes.
One strategy to improve the conditions under which Rh(I)-
catalyzed nucleophilic additions of C-B reagents can occur,
is to utilize more reactive boron reagents. Such reagents
would also be useful for optimization studies, new catalyst
development, asymmetric variants, and applications to com-
binatorial library synthesis. Organotrifluoroborate salts
(RBF3M, M ) alkali metal) have only recently been applied
in organic synthesis.4a,5 Advantages of these reagents com-
pared to the corresponding boronic acids, are their greater
stability to air/water,4a,5f,h their ease of isolation, and the
avoidance of trimer formation that can occur with boronic
acids. With these potential advantages in mind, we decided
(1) For reviews, see: (a) Devant, R. M.; Radunz, H.-E. In Houben-Weyl,
StereoselectiVe Synthesis; Helmchen, G., Hoffmann, R. W., Mulzer, J.,
Schaumann, E., Eds.; Georg Thieme Verlag Stuttgart: Stuttgart, Germany,
1995; Vol. E21, pp 1151-1334. (b) Yamamoto, Y. In Houben-Weyl,
StereoselectiVe Synthesis; Helmchen, G., Hoffmann, R. W., Schaumann,
E., Eds.; Georg Thieme Verlag Stuttgart: Stuttgart, Germany, 1995; Vol.
E21, pp 2041-2067.
(2) Sakai, M.; Euda, M.; Miyaura, N. Angew. Chem., Int. Ed. 1998, 37,
3279-3281.
(3) (a) Sakai, M.; Hayashi, H.; Miyaura, N. Organometallics 1997, 16,
4229-4331. (b) Takaya, Y.; Ogasawara, M.; Hayashi, T.; Sakai, M.;
Miyaura, N. J. Am. Chem. Soc. 1998, 120, 3379-3380. (c) Takaya, Y.;
Ogasawara, M.; Hayashi, T. Tetrahedron Lett. 1998, 39, 8479-8482.
(4) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Tetrahedron Lett. 1999,
40, 4289-4292. (b) Batey, R. A.; MacKay, D. B.; Santhakumar, V. J. Am.
Chem. Soc. 1999, 121, 5075-5076. (c) Batey, R. A.; Thadani, A. N.; Lough,
A. J. J. Am. Chem. Soc. 1999, 121, 450-451. (d) Batey, R. A.; Smil, D. V.
Angew. Chem., Int. Ed. 1999, 38, 1798-1800. (e) Batey, R. A.; Thadani,
A. N.; Lough, A. J. Chem. Commun. 1999, 475-476.
10.1021/ol9910767 CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/10/1999

to explore the utility of organotrifluoroborates as nucleophiles
in the aforementioned Rh(I)-catalyzed reactions to extend
the scope of this useful transformation (Scheme 1).
Table 1. Comparative Efficiency of Conjugate Addition of
Potassium Phenyltrifluoroborate and Phenylboronic Acid to
Methyl Vinyl Ketone
Scheme 1
yield (%) of 2a a
t (h)
PhBF3-K+ (1a )
PhB(OH)2
1
4
8
16
52
79
91
11
39
56
82b
16
The formation of the potassium alkenyl- and aryltrifluoro-
borates 1 was achieved via the corresponding boronic acids
as first described by Vedejs and co-workers.5a The requisite
boronic acids were either commercially available or readily
prepared by standard hydroboration methodology (Scheme
2).
a Isolated Yields. b 99% GC yield reported in ref 3a.
dropping slightly to 84% after 16 h. Reaction with Wilkin-
son’s catalyst (Aldrich Chemicals, 3 mol %) resulted in a
42% isolated yield of 2a after 16 h. Reduction of the amount
of trifluoroborate salt 1a to 1.1 equiv resulted in a modest
drop in the isolated product yield to 82%. When the reaction
was conducted in dry DME or with just 10 equiv of water,
the reaction was slower, with product to starting material
ratios at 16 h of 25:75 and 80:20, respectively.
Scheme 2
Other potassium alkenyl- and aryltrifluoroborates 1 also
reacted with MVK using the standard protocol, giving
comparable isolated yields of the products 2 (Table 2).
Table 2. Conjugate Arylation and Alkenylation of MVK with
Potassium Aryl- and Alkenyltrifluoroborates
To focus upon the effect of the boron-based reagent on
conjugate additions to enones, we elected to use the same
catalyst and reaction conditions as those reported by Miyaura
and co-workers.3a Potassium phenyltrifluoroborate 1a and
methyl vinyl ketone (MVK) were chosen as representative
substrates. By using 2 equiv of 1a in the presence of
Rh(acac)(CO)2 (3 mol %) and 1,4-bis(diphenylphosphino)-
butane (dppb) (3 mol %), reaction proceeded to full conver-
sion after 16 h in MeOH/water (6:1) at 50 °C. The relative
rate of reaction for 1a was greater than that for phenylboronic
acid under otherwise identical conditions, as determined at
1, 4, 8, and 16 h (Table 1).
The reaction was also effective using triphenylphosphine
as a ligand (2 equivalents), with the isolated yield of 2a
(5) (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf, M.
R. J. Org. Chem. 1995, 60, 3020-3027, and references therein. (b) Vedejs,
E.; Fields, S. C.; Hayashi, R.; Hitchcock, R.; Powell, D. R.; Schrimpf, M.
R. J. Am. Chem. Soc. 1999, 121, 2460-2470. (c) Petasis, N. A.; Yudin, A.
K.; Zavialov, I. A.; Prakash, G. K. S.; Olah, G. A. Synlett 1997, 606-608.
(d) Darses, S.; Geneˆt, J.-P. Tetrahedron Lett. 1997, 38, 4393-4396. (e)
Darses, S.; Michaud, G.; Geneˆt, J.-P. Tetrahedron Lett. 1998, 39, 5045-
5048. (f) Darses, S.; Michaud, G.; Geneˆt, J.-P. Eur. J. Org. Chem. 1999, 5,
1875-1883. (g) Xia, M.; Chen, Z.-C. Synth. Commun. 1999, 29, 2457-
2465. (h) Chambers, R. D.; Clark, H. C.; Willis, C. J. J. Am. Chem. Soc.
1960, 82, 5298-5301.
Particularly noteworthy is the addition of the electron-
deficient trifluoroborate 1b to MVK. We determined that
the corresponding 3-nitrophenylboronic acid does not add
1684
Org. Lett., Vol. 1, No. 10, 1999

under otherwise identical conditions, demonstrating the
greater reactivity of the tetracoordinate trifluoroborate salts
for the conjugate additions.
(Table 4).6 The use of 2 equiv of the trifluoroborate salt was
again found to be optimal, with the isolated yields of 3a
Having established the feasibility of Rh(I)-catalyzed
conjugate addition of 1 to MVK, we briefly studied the scope
of the process with terminally monosubstituted and cyclic
enones as substrates. Under the optimized conditions, cyclo-
hexenone and (E)-4-phenyl-3-buten-2-one reacted with 1f
and 1a, respectively, to furnish the substituted ketones 2g
and 2h in high yield (Scheme 3).
Table 4. Arylation and Alkenylation of Aldehydes with
Potassium Aryl- and Alkenyltrifluoroborates
yield (%)
entry
R1BF3-K+
R2
(aldehyde)
1
2
3
4
5
6
7
8
9
1a
1a
1e
1a
1a
1d
1a
1d
1f
Ph
79 (3a )
85 (3b)
82 (3c)
88 (3d )
85 (3e)
88 (3f)
87 (3g)
85 (3h )
80 (3i)
71 (3j)
71 (3k )
86 (3l)
Scheme 3
4-O2NC6H4
4-O2NC6H4
3-O2NC6H4
2-O2NC6H4
2-O2NC6H4
4-NCC6H4
4-NCC6H4
4-NCC6H4
4-MeOOCC6H4
4-MeOOCC6H4
C6H11
10
11
12
1a
1e
1a
The potassium trifluoroborate salts 1 were also useful
reagents for nucleophilic additions to aldehydes. For initial
studies we again opted to adapt the conditions developed
by Miyaura and co-workers for the alkenylation and arylation
of aldehydes.2 Reaction of benzaldehyde with 2 equiv of 1a
with Rh(acac)(CO)2 (3 mol %) and 1,1′-bis(diphenylphos-
phino)ferrocene (dppf) (3 mol %) resulted in the formation
of 3a. The reaction proceeded to full conversion after 16 h
in DME/water (1:1) at 80 °C. The trifluoroborate salt 1a is
again more reactive than phenylboronic acid (Table 3). When
dropping to 69% and 28% with 1.5 and 1.1 equiv of 1a
respectively. Nitro-substituted aldehydes that reacted ef-
ficiently in our studies were found to be unreactive when
the corresponding boronic acids were used under otherwise
identical conditions.2
Finally, we briefly studied the effect of the ligand upon
the reaction of phenyltrifluoroborate 1a with 4-nitrobenz-
aldehyde. Significantly, the ligands dppb (1 equiv) and
triphenylphosphine (2 equiv) were found to be effective in
the reaction, with yields dropping from 85% with dppf to
83% with PPh3 and 76% with dppb. This is in sharp contrast
to the results obtained in the addition of phenylboronic acid
to aldehydes, in which no reaction occurs with PPh3 as a
ligand.2 This suggests that the P-Rh-P angle does not
significantly affect catalyst activity under our conditions, an
observation which may be useful in the design of more active
or asymmetric catalysts for the reaction.
Table 3. Comparative Efficiency of Potassium
Phenyltrifluoroborate and Phenylboronic Acid Addition to
Benzaldehyde
The greater effectiveness of the potassium trifluoroborate
salts in the Rh(I) catalyzed additions to enones and aldehydes,
compared to the boronic acids, presumably reflects more
facile transmetalation to form the active Rh-C species.
Although a full mechanistic study is required to confirm this
hypothesis, other tetracoordinate boron compounds may
offer a similar improvement in reactivity.
conversion (%)a
t (h)
PhBF3-K+
PhB(OH)2
1
4
8
20
75
90
<10
20
45
In conclusion, we have successfully demonstrated the
viability of alkenyl- and aryltrifluoroborates as air- and
16
>99
>98
a Determined by H NMR of the crude reaction mixture.
1
(6) Representative Procedure. A suspension of potassium 3-thiophene-
trifluoroborate 1f (323 mg, 2.00 mmol) and 4-cyanobenzaldehyde (131 mg,
1.00 mmol), Rh(acac)(CO)2 (8 mg, 0.03 mmol), and dppf (17 mg, 0.03
mmol) in a 1:1 mixture of DME/water (6 mL) was stirred at 80 °C for 16
h. The reaction mixture was then diluted with benzene (20 mL), and the
layers were separated. The aqueous layer was extracted with benzene (3 ×
5 mL). The combined organic extracts were dried (MgSO4), filtered, and
concentrated in vacuo to afford a brown oil. Silica gel chromatography
(20% EtOAc/80% hexanes) afforded 3i as a clear, colorless oil (172 mg,
80%).
1a was used, conversion was almost complete after 8 h,
whereas less than half of the aldehyde had undergone reaction
with phenylboronic acid.
A variety of aldehydes were functionalized in this manner
to give the corresponding allylic and benzylic alcohols 3
Org. Lett., Vol. 1, No. 10, 1999
1685

moisture-stable agents for nucleophilic additions to enones
and aldehydes. This is a significant practical improvement
over existing conditions, expanding the scope of substrates
which can be applied in the reaction, and further validating
the utility of this very important transition metal-catalyzed
reaction. We are currently working toward establishing the
nature of the active intermediates within the catalytic cycle
and the development of asymmetric variants for the additions
to aldehydes. Extensions of this methodology to other
substrates, and its application in combinatorial synthesis will
also be reported in due course.
of Canada. A.N.T. thanks the NSERC of Canada for a
postgraduate scholarship. R.A.B. gratefully acknowledges
AstraZeneca, AstraZeneca R&D Montre´al, Bio-Me´ga/
Boehringer Ingelheim Recherche Inc., the Environmental
Science and Technology Alliance Canada, Merck-Frosst, the
Ontario Research and Development Challenge Fund, and
Uniroyal Chemicals Inc. for additional support. We thank
Dr. A. B. Young for mass spectroscopic analyses.
Supporting Information Available: Preparation proce-
dures and characterization data for 1b-d, 1f, 2a-f, and 3a-
l. This material is available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgment. This work was supported by the
National Science and Engineering Research Council (NSERC)
OL9910767
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Org. Lett., Vol. 1, No. 10, 1999