Pd-catalyzed cross-coupling of Baylis-Hillman acetate adducts with bis(pinacolato)diboron: An efficient route to functionalized allyl borates

Article abstract of DOI:10.1021/jo0492618

The cross-coupling of Baylis-Hillman acetate adducts and bis(pinacolato)diboron proceeds readily in high yields in the presence of palladium catalyst to produce 3-substituted-2-alkoxycarbonyl allylboronates. These allylboronates can be transformed to stab

Full text of DOI:10.1021/jo0492618

TABLE 1. Op tim izin g Rea ction Con d ition s for th e
P r ep a r a tion of Allylbor on a te 3a fr om Ba ylis-Hillm a n
a d d u ct 1a
P d -Ca ta lyzed Cr oss-Cou p lin g of
Ba ylis-Hillm a n Aceta te Ad d u cts w ith
Bis(p in a cola to)d ibor on : An Efficien t Rou te
to F u n ction a lized Allyl Bor a tes
George W. Kabalka,* Bollu Venkataiah, and Gang Dong
The University of Tennessee, Departments of Chemistry and
Radiology, Knoxville, Tennessee 37996-1600
solvent
catalysta
ligandb
yield (GC-MS)
kabalka@utk.edu
THF
THF
THF
THF
THF
THF
ether
toluene
Toluene
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2
PdCl2(dppf)
Pd2(dba)3c
Pd(OAc)2
PPh3
dppf
36
48
92
0
Received April 30, 2004
0
Abst r a ct : The cross-coupling of Baylis-Hillman acetate
adducts and bis(pinacolato)diboron proceeds readily in high
yields in the presence of palladium catalyst to produce
95
82
96
96
Pd(OAc)2
3
-substituted-2-alkoxycarbonyl allylboronates. These allyl-
Pd2(dba)3c
boronates can be transformed to stable allyl trifluoroborate
salts by addition of excess aqueous KHF2. Both the allylbo-
ronate and allyltrifluoroborate derivatives react with alde-
hydes to afford functionalized homoallylic alcohols stereo-
selectively.
a
b
5
mol % catalyst was used unless otherwise mentioned. 10
c
mol % ligand was used. 3 mol % catalyst was used.
2
-alkoxycarbonylallylboronates by carbocupration of
1
0
alkynoate esters. These results encouraged us to in-
vestigate the preparation of substituted 2-alkoxycarbonyl
allylboron reagents from Baylis-Hillman adducts.
The Baylis-Hillman reaction has great synthetic util-
ity as it converts simple starting materials into densely
functionalized products11 that are useful in a variety of
synthetic transformations. In a continuation of our study
of reactions involving organoboron reagents,1 we inves-
tigated the cross-coupling reaction of bis(pinacolato)di-
boron, 2, with acetates of Baylis-Hillman adducts 1 in
the presence of palladium to form highly functionalized
allyl boronates and the corresponding trifluoroborates.
The preparation of allylboronate 3a using the Baylis-
Hillman adduct methyl 3-acetoxy-3-phenyl-2-methylene-
propanoate, 1a , and bis(pinacolato)diboron in the pres-
ence of different palladium catalysts was first investi-
Allylmetal reagents of boron, silicon, and tin have
found widespread use in organic synthesis. The addition
1
of allylmetal reagents to carbonyl compounds has proven
to be enormously successful for the synthesis of homoal-
lylic alcohols and is widely used in organic synthesis.
Among allylmetal reagents, allylboron compounds are
very useful because of the high yield and excellent
stereocontrol they provide in reactions with carbonyl
compounds via a six-membered, cyclic chair transition
state characterized by internal activation of the aldehyde
2
2
3
4
5
by the boron. Brown, Hoffman, and Roush investi-
gated this transformation in detail. However, availability
of functionalized allylboron reagents remains limited. In
addition to traditional methods,5
a,6
the prerequisite al-
lylboronates can be prepared via transition metal medi-
gated (Table 1).13 Among the catalysts used, Pd(OAc)
Pd (dba) worked well without additional ligand require-
ments. The reactions were most efficient in THF and tol-
uene. The highest yields were obtained utilizing Pd (dba)
and
7
2
ated processes, cross-metathesis reactions of olefins and
8
2
3
allylboronates, and a three-component assembly of al-
9
lenes, acyl chlorides, and bis(pinacolato)diboron. Re-
2
3
,
cently, Kennedy and Hall reported the preparation of
but the allylboronate products readily decomposed during
*
To whom correspondence should be addressed. Phone: (865) 974-
260. Fax: (865)974-2997.
1) (a) Denmark, S. E.; Fu, J . Chem. Rev. 2003, 103, 2763. (b)
Kennedy, J . W. J .; Hall, D. G. Angew. Chem., Int. Ed. 2003, 42, 4732.
3
(7) (a) Watanabe, T.; Miyaura, N.; Suzuki, A. J . Organomet. Chem.
1993, 444, C1. (b) Falck, J . R.; Bondlela, M.; Ye, J .; Cho, S. D.
Tetrahedron Lett. 1999, 40, 5647. (c) Ishiyama, T.; Ahiko, T. A.;
Miyaura, N. Tetrahedron Lett. 1996, 37, 6889. (d) Sebelius, S.; Wallner,
O. A.; Szabo, K. J . Org. Lett. 2003, 5, 3065.
(
(
2) Li, Y.; Houk, K. N. J . Am. Chem. Soc. 1989, 111, 1236.
(3) (a) Brown, H. C.; Bhat, K. S. J . Am. Chem. Soc. 1986, 108, 293.
(
1
b) Brown, H. C.; J adhav, P. K.; Bhat, K. S. J . Am. Chem. Soc. 1988,
10, 1535. (c) Brown, H. C.; Racherla, U. S.; Pellechia, P. J . J . Org.
Chem. 1990, 55, 1868.
4) (a) Hoffmann, R. W.; Zeiss, H. J . Angew. Chem., Int. Ed. Engl.
(8) Goldberg, S. D.; Grubbs, R. H. Angew. Chem., Int. Ed. 2002, 41,
807.
(9) Yang, F.-Y.; Wu, M.-Y.; Cheng, C.-H. J . Am. Chem. Soc. 2000,
122, 7122.
(
1
2
980, 19, 218. (b) Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1982,
1, 555. (c) Hoffmann, R. W. Pure Appl. Chem. 1988, 60, 123.
(10) Kennedy, J . W. J .; Hall, D. G. J . Am. Chem. Soc. 2002, 124,
898.
(
5) (a) Roush, W. R.; Adam, M. A.; Walts, A. E.; Harris, D. J . J . Am.
(11) (a) Drewes, S. E.; Ross, G. H. P. Tetrahedron 1988, 44, 4653.
(b) Basavaiah, D.; Rao, A. J .; Satyanarayana, T. Chem. Rev. 2003, 103,
811.
Chem. Soc. 1986, 108, 3422. (b) Roush, W. R.; Banfi, L.; Park, J . C.;
Hoong, L. K. Tetrahedron Lett. 1989, 30, 6457. (c) Roush, W. R.; Ando,
K.; Powers, D. B.; Polkowitz, A. D.; Halterman, R. L. J . Am. Chem.
Soc. 1990, 112, 6339.
(12) (a) Yu, S.; Li, N.-S.; Kabalka, G. W. J . Org. Chem. 1999, 64,
5822. (b) Kabalka, G. W.; Wu, Z.; J u, Y. Org. Lett. 2002, 4, 3415. (c)
Kabalka, G. W.; Dong, G.; Venkataiah, B. Org. Lett. 2003, 5, 893. (d)
Kabalka, G. W.; Guchhait, S. K. Org. Lett. 2003, 5, 4129.
(13) During preparation of this manuscript a related synthesis of
allylboronates, 3, using copper catalysts was reported: Ramachandran,
P. V.; Pratihar, D.; Biswas, D.; Srivastava, A.; Reddy, M. V. R. Org.
Lett. 2004, 6, 481.
(
6) (a) Brown, H. C.; DeLue, N. R.; Yamamoto, Y.; Maruyama, K.;
Kasahara, T.; Murahashi, S.-I.; Sonda, A. J . Org. Chem. 1977, 42, 4088.
b) Matteson, D. S.; Majumdar, D. Organometallics 1983, 2, 230. (c)
Hoffmann, R. W.; Zeiss, H. J . Angew. Chem., Int. Ed. Engl. 1979, 18,
(
3
1
06. (d) Wuts, P. G. M.; Thompson, P. A.; Callen, G. R. J . Org. Chem.
983, 48, 8, 5400.
1
0.1021/jo0492618 CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/29/2004
J . Org. Chem. 2004, 69, 5807-5809
5807

TABLE 2. P r ep a r a tion of Su bstitu ted Allylbor on Rea gen ts fr om Ba ylis-Hillm a n Aceta te Ad d u cts (1)a
a
b
The cross-coupling reaction was performed at 50 °C for 3 h using 5 mol % Pd(OAc)2 in THF unless otherwise noted. Struc-
tures confirmed using spectral ( H, C, F) analyses. c 3 mol % Pd2(dba)3 used. d E:Z ratio is 97:3. e Reaction time was 6 h. GC-MS
yield.
1
13
19
f
8
silica gel chromatography. To solve this problem, we
trifluoroborate derivatives, 4 (Scheme 1). Trifluoroborates
are air- and moisture-stable but chemically reactive.
1
4,15
converted the boronate products, 3, to the corresponding
5
808 J . Org. Chem., Vol. 69, No. 17, 2004

SCHEME 1
SCHEME 2
The reaction procedure is straightforward. The Baylis-
Hillman acetate adduct 1 is allowed to react with bis-
Allyl trifluoroborate salt 4, prepared using the present
method, reacts with p-nitrobenzaldehyde in the presence
of tetrabutylammonium iodide to give the corresponding
homoallylic alcohols in high yield with excellent diaste-
reoselectivity (eq 1, Scheme 2).1 We also studied al-
lylboration reactions without isolating the boron inter-
mediates (eq 2).18 For example, addition of p-nitrobenzalde-
hyde to the crude cross-coupling reaction mixture readily
(pinacolato)diboron in the presence of 5 mol % Pd(OAc)
2
or 3 mol % Pd (dba) in THF at 50 °C for 3 h. This
2
3
5c
produces 2-alkoxycarbonyl-3-substituted allylboronate
pinacol ester 3, which is then treated with excess aqueous
KHF and stirred at room temperature for 20 min to
2
obtain the (E)-2-alkoxy-3-substituted allyltrifluoroborate
potassium salt 4. The stereochemistry of the allylbor-
furnished the corresponding homoallylic alcohols in the
1
13
19
onate was determined to be E, using H and C spec-
presence of 30 mol % BF
3
2
‚Et O at room temperature.
1
6
troscopy as well as protonolysis. The results are con-
In conclusion, we have shown that Baylis-Hillman
acetate adducts couple with bis(pinacolato)diboron to give
3-substituted-2-alkoxycarbonyl allylboronates 3, which
can be transformed into air- and water-stable allyltrif-
sistent with earlier studies.1
4c,17
It is important to note
that allyl trifluoroborate salts are air- and water-stable
solids and can be stored at room temperature, whereas
allylboronates are unstable to moisture.
2
luoroborate salts 4 by addition of aqueous KHF . Alter-
Several types of Baylis-Hillman acetate adducts readily
participate in the reaction. As shown in Table 2, Baylis-
Hillman acetate adducts derived from methyl acrylate
natively, they can be utilized directly in allylboration
reactions with carbonyl compounds to obtain highly
functionalized homoallylic alcohols 5. It is noteworthy
that the reaction is E-stereoselective and is applicable
to Baylis-Hillman acetate adducts derived from aryl,
heteroaryl, and aliphilic aldehydes.
(1a -h ) and methyl vinyl ketone 1i were transformed into
the corresponding (E)-allylborates.
(
14) (a) Vedejs, E.; Chapman, R. W.; Fields, S. C.; Lin, S.; Schrimpf,
Ack n ow led gm en t. We thank the Robert H. Cole
foundation for support of this research.
M. R. J . Org. Chem. 1995, 60, 3020. (b) Molander, G. A.; Bernardi, C.
R. J . Org. Chem. 2002, 67, 8424. (c) Molander, G. A.; Ribagorda, M. J .
Am. Chem. Soc. 2003, 125, 11148. (d) Darses, S.; Genet, J .-P. Eur. J .
Org. Chem. 2003, 4313. (e) Kabalka, G. W.; Venkataiah, B.; Dong, G.
Org. Lett. 2003, 5, 3803.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic data for compounds, 4a -g, 4i, 5a ,
and 5h . This material is available free of charge via the
Internet at http://pubs.acs.org.
(
15) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Tetrahedron Lett.
999, 40, 4289. (b) Lautens, M.; Raeppel, S.; Quellet, S. Angew. Chem.
Int. Ed.. 2000, 39, 4079. (c) Thadani, A. N.; Batey, R. A. Org. Lett.
002, 4, 3827.
16) Reaction of Baylis-Hillman adduct 1a with bis(pinacolato)-
diboron in the presence of Pd(OAc) in THF gave allylboronate 3a in
1
2
J O0492618
(
2
(18) In both cases (Scheme 2, eqs 1 and 2) the diastereoselectivity
1
9
2% yield (GC-MS); however, when the reaction mixture was exposed
to air, formation of (E)-2-methyl cinnamic acid methyl ester from 3a
was observed.
(
was found to be >98% by H NMR analysis.
(19) (a) Kennedy, J . W. J .; Hall, D. G. J . Am. Chem. Soc. 2002, 124,
11586. (b) Ishiyama, T.; Ahiko, T.-A.; Miyaura, N. J . Am. Chem. Soc.
2002, 124, 12414. (c) Lachance, H.; Lu, X.; Gravel, M.; Hall, D. G. J .
Am. Chem. Soc. 2003, 125, 10160.
17) Wang, S.-Z.; Yamamoto, K.; Yamada, H.; Takahashi, T. Tetra-
hedron 1992, 48, 2333.
J . Org. Chem, Vol. 69, No. 17, 2004 5809