J. A m . Chem. SOC.1989, 1 1 1 , 314-321
314
Palladium-Catalyzed Inter- and Intramolecular Cross-Coupling Reactions of B-Alkyl-9-borabicyclo[ 3.3.1 Inonane Derivatives with 1-Halo- 1-alkenes or Haloarenes. Syntheses of Functionalized Alkenes, Arenes, and Cycloalkenes via a Hydroboration-Coupling Sequence' Norio Miyaura, Tatsuo Ishiyama, Hirotomo Sasaki, Masako Ishikawa, Makoto Satoh, and Akira Suzuki* Contribution from the Department of Applied Chemistry, Faculty of Engineering, Hokkaido University, Sapporo 060, Japan. Received March 28, I988
Abstract: The cross-coupling reaction of B-alkyl-9-borabicyclo[3.3.l]nonanes(B-R-9-BBN), readily obtainable from alkenes by hydroboration, with 1-halo-1-alkenes or haloarenes in the presence of a catalytic amount of PdCl,(dppf) and bases, such as sodium hydroxide, potassium carbonate, and phosphate, gave the corresponding alkenes or arenes. Because the reaction is tolerant of a variety of functionalities on either coupling partner, stereochemically pure functionalized alkenes and arenes can be obtained under mild conditions. The utility of the reaction was demonstrated by the stereoselective synthesis of 1,5-alkadienes (7 and 8) and the extension of a side chain in a steroid (11). The hydroboration of haloalkadienes (12), followed by the intramolecular cross-coupling, gave a short-step procedure for synthesis of cycloalkenes, benzo-fused cycloalkenes, and exocyclic alkenes (14 and 16).
T h e cross-coupling reaction2 of organic electrophiles with organometallic reagents in the presence of transition metals is a very mild and most straightforward method of forming carbon-carbon bonds. Although organometallic reagents with alkyl, I-alkenyl, I-alkynyl, and aryl groups have been successfully used for the coupling reactions, those with alkyl groups having sp3 carbons containing 6 hydrogens have been severely limited due to the competive side reactions. Rm
+
ML"
R'X
R= alkyl
R'=
R-R'
alkenyl, aryl
(1)
M: Ni, Pd, Fe
In 1971-1972, K ~ c h i K, ~~ m a d a and , ~ Corriu5 reported independently that the reaction of alkyl Grignard reagents with alkenyl or aryl halides could be markedly catalyzed by Fe(II1) or Ni(I1) complexes. Recent studies by Negishi6 demonstrated the synthetic utility of alkylzincs by use of palladium catalyst. Alkyllithium,' (1) Preliminary communication of this work has appeared: Miyaura, N.; Ishiyama, T.; Ishikawa, M.; Suzuki, A. Tetrahedron Lett. 1986, 27, 6369. (2) For general reviews, see: (a) Collman, J. P.; Hegedus, L. S. Principles, and Applications of Organotransition Metal Chemistry; University Science Books: Mill Valley, CA, 1980. (b) Tsuji, J. Organic Synthesis with Palladium Compounds; Springer-Verlag: Berlin, 1980. (c) Kochi, J. K. Organometallic Mechanisms, and Catalysts; Academic: New York, 1978. (d) Heck, R. F. Palladium Reagents in Organic Syntheses; Academic: New York, 1985. (e) Hartley, F. R. The Chemistry of the Metal-Carbon Bond Patai, S., Ed.; Wiley: New York, 1985. (3) (a) Tamura, M.; Kochi, J. K. J . Am. Chem. SOC.1971, 93, 1487. (b) Tamura. M.; Kochi, J. K. Synthesis 1971,303. (c) Kochi. J. K. Acc. Chem. Res. 1974, 7, 351. (d) Neumann, S. M.; Kochi,'J. K. J . Org. Chem. 1975, 40, 599. (e) Kwan, C. L.; Kochi, J. K. J . A m . Chem. SOC.1976, 98, 4903. (4) (a) Tamao, K.; Sumitani, K.; Kumada, M. J . Am. Chem. SOC.1972, 94, 4374. (b) Tamao, K.; Zembayashi, M.; Kiso, Y.; Kumada, M. J . Organomet. Chem. 1973,55, C91. (c) Tamao, K.; Kiso, Y.; Sumitani, K.; Kumada, M. J . A m . Chem. SOC.1972, 94, 9268. (d) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.; Fujioka, A,; Komada, S.; Nakajima, I.; Minato, A,; Kumada, M. Bull. Chem. SOC.Jpn. 1976, 49, 1958. (e) Kumada, M . Pure Appl. Chem. 1980, 52, 669. (f) Hayashi, T.; Konishi, M.; Fukushima, M., Mise. T.: Kaaotani. M.: Taiika. M.: Kumada. M. J . A m . Chem. SOC.1982. 104, 180: (gy Hayashi,'T.;Konishi,' M.; Kobori, Y.; Kumada, M.; Higuchi; T.: Hirotsu. K. Ibid. 1984. 106. 158. '(5) Corriu, R. J. P ; Masse, J:P. J . Chem. SOC.,Chem. Commun. 1972, 144. (6) (a) Negishi, E.; Valente, L. F.; Kobayashi, M. J . Am. Chem. SOC.1980, 102, 3298. (b) Kobayashi, M.; Negishi, E. J . Org. Chem. 1980, 45, 5223. (c) Negishi, E. Acc. Chem. Res. 1982, 15, 340. (7) (a) Murahashi, S.; Yamamura, M.; Yanagisawa, K.; Mita, N.; Kondo, K. J . Org. Chem. 1979,44, 2408. (b) Kondo, K.; Murahashi, S. Tetrahedron Lett. 1979, 1237. 0002-7863/89/1511-03 14$01.50/0
Table I. Reaction Conditions: Cross-Coupling of B-Octyl-9-BBN with
Iodobenzene (Eq 2)O base % temp, catalvst (eauiv) solvent yieldb OC 1 99 65 PdC12(dppf) NaOH (3) THF-H,O (5:l) 2 20 19 PdCli(dppf) TlOH (1.5) THF-Hi0 (5:l) 65 98 3 PdCl;(dppf) NaOMe (1.5) THF 4 PdCl,(dppf) NaOMe (1.5) THF-MeOH (5:l) 65 18 5 PdCl,(dppf) K2CO3 (2) DMF 50 98 94 50 DMF 6 PdC12(dppf) K3P0, 84 65 NaOH (3) THF-H,O ( 9 1 ) 7 Pd(PPh3), 97 80 NaOH (31 benzene-H,O 8 Pd(PPh2L "Reactions were carried out in 5 mL of solvent for 16 h with 3 mol % of palladium catalyst, bases, iodobenzene (1 mmol), and B-octyl-9-BBN (1.1 mmol). *GLC yields are based on the iodobenzene employed.
entry -
~A
-tin,* and-aluminum9 reagents were also used for the cross-coupling reactions. Among these studies dichloro[ 1,3-bis(diphenylphosphino)propane]nickel(II) [NiC12(dppp)14' and dichloro[l,l'-bis(diphenylphosphino)ferrocene]pa~ladium(II) [PdCI2( d ~ p f ) ] , ~reported g by Kumada, Tamao, and Hayashi, a r e recognized a s the most selective catalysts, which suppress the unavoidable side reactions, e.g., the isomerization of alkyl groups and the reduction of halides, caused by hydridopalladium species generated by 6-hydride elimination from alkylpalladium complexes. T h e alkyl-aryl or alkyl-alkenyl coupling involving secondary or even tertiary alkylmagnesium halides proceeds selectively. The recent discovery by Castle and Widdowsonlo that even alkyl iodides undergo the coupling reaction with Grignard reagents in the presence of PdC12(dppf) should be a great success of this catalyst in the field of the cross-coupling reaction. W e have previously reported the palladium-catalyzed crosscoupling reaction of 1-alkenyl-" and arylboronI2 compounds with (8) (a) Kosugi, M.; Simizu, Y.; Migita, T. Chem. Lett. 1977, 1423. (b) Kosugi, M.; Hagiwara, I.; Migita, T. Ibid. 1983, 839. (c) Milstein, D.; Stille, J. K. J . Am. Chem. SOC.1979, 101, 4992. (d) Scott, W. J.; Crisp, G. T.; Stille, J. K. Ibid. 1984, 106, 4630. (e) Scott, W. J.; Stille, J . K. Ibid. 1986, 108, 3033. (f) Echavarren, A. M.; Stille, J. K. Ibid. 1987, 109 5478. (9) (a) Giacomelli, G.; Lardicci, L. Tetrahedron Lett. 1978, 19, 2831. (b) Takai, K.; Oshima, K.; Nozaki, H. Ibid. 1980, 21, 2531. (IO) Castle, P.L.; Widdowson, D. A. Tetrahedron Lett. 1986, 27, 6013. (11) (a) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J . A m . Chem. SOC.1985, 107, 972. (b) Miyaura, N.; Suginome, H.; Suzuki, A. Tetrahedron 1983, 39, 3271. (c) Miyaura, N.; Satoh, M.; Suzuki, A. Tetrahedron Lett. 1986,27,3745. (d) Satoh, M.; Miyaura, N.; Suzuki, A. Chem. Lett. 1986, 1329. (e) Ishiyama, T.; Miyaura, N.; Suzuki, A. Ibid. 1987, 25. (f) Suzuki, A. Arc. Chem. Res. 1982, 15, 178. (g) Suzuki, A. Pure Appl. Chem. 1985, 57, 1749.
0 1989 American Chemical Society
J . A m . Chem. SOC.,Vol. 1 1 1 , No. 1 , 1989 315
Cross-Coupling Reactions of' B - A l k y l - 9- BBN Dericatiues organic halides. T h e reaction proceeds readily and stereo- and i egioselectively to give conjugated alkadienes or alkenynes in high yields. T h e configuration of both the haloalkenes and l-alkenylboranes are retained during the reaction, thus providing versatile and reliable procedures for the syntheses of stereodefined conjugated (E,E)-, (E,Z)-, (Z,E)-, and (2,Z)-alkadienes and enynes under mild conditions." However, organoboranes with alkyl groups have not been used successfully for the coupling reaction. Alkylboranes are readily prepared by h y d r o b o ~ a t i o n of ' ~ alkenes, which is essentially quantitative, proceeds through a &-Markovnikov addition from the less hindered side of double bond, and can tolerate various functional groups. Since alkylboranes thus obtained are also quite inert toward many functional groups, the couplings can be carried out without protecting these groups. Herein, we report on the scope and limitations of the palladiumcatalyzed coupling reaction of such alkylboranes with haloalkenes or haloarenes, a s well as its synthetic application.
Table 11. Coupling Reaction of lodobenzene with Various B-Alkylboron Compoundsu entrv borane 7c yieldb
Results and Discussion
OReactions were conducted in T H F at refluxing temperature with 3 mol % of PdCl,(dppf), 3 M NaOH in H,O (I mL), iodoben~ene( I mmol), and 8-alkylboron compounds ( 1 . 1 mrnol). unless otherui\e noted. b C L C yields are based on the iodobenzene employed. '3 M KOH in H 2 0 (1 mL) was used as a base. Biphenyl (10-30%) was also obtained.
Reaction Conditions. A series of reactions was examined with llnonane (B-octyl-9iodobenzene and B-octyl-9-borabicyclo[3.3. BBK] as partners to establish the reaction conditions (eq 2 and Table I). As reported previously,' iodobenzene coupled in high Phi
+
CBdYI
-
Ph(CH,hCH,
(2)
yields with B-octyl-9-BBN in the presence of 1-3 mol % of PdCl,(dppf) and 3 equiv of sodium hydroxide in refluxing THF-water (5:l) to give octylbenzene. T h e base is essential for the success of the reaction. T h e reaction did not proceed a t a detectable rate in the absence of a base, and the reaction also failed when weak bases such a s sodium acetate were used. Thallium(1) hydroxide, successfully utilized by Kishi14 for the cross-coupling reaction of 1-alkenylboronic acids, also accelerated the reaction even a t room temperature. W h e n there a r e no functionalities sensitive to bases on either the alkylboranes or the organic halides, a combination of PdCl,(dppf) and sodium hydroxide in T H F - H 2 0 worked nicely in most cases. For the functionalized alkylboranes and halides, aprotic conditions were desirable. Although it was found that powdered sodium methoxide suspended in THF accelerated the reaction with iodobenzene, such conditions were less effective with vinylic halides, as shown later. A more promising coupling was achieved by using powdered potassium carbonate or phosphate suspended in D M F a t 50 OC (Table I, entries 5 and 6). Under these conditions, a wide variety of functional groups, such as ester, cyano, and carbonyl groups, can be tolerated on either coupling partner as shown in Tables I11 and IV. Although PdC12(dppf) was used in most of the present work, Pd(PPh,), is perhaps more commonly used for such a coupling reaction. The reaction in the presence of 3 mol% of Pd(PPh3)4 and sodium hydroxide in benzene gave octylbenzene in a yield of 97% (entry 8 in Table I). A comparison of various B-octylylboron compounds in the reaction with iodobenzene demonstrated that the representative hydroborating reagents, such as 9-BBN, disiamylborane, dicyclohexylborane, and borane, can be used for the present reaction (entries 1-4 in Table 11). O n e of three alkyl groups in tri(12) Miyaura, N.; Yanagi. T.;Suzuki, A. Synth. Commun. 1981, I ! , 513. See also: (a) Gronowitz, S.: Lawitz, K. Chem. Scr. 1983, 22, 265. (b) Thompson, W . J.; Gaudino, J. J . Org. Chem. 1984, 49, 5237. (c) Ishikura, M.; Kamada, M.: Terashirna, M. Synthesis 1984, 936. (d) Miller, R. B.; Dugar, S. Organomerallics 1984, 3, 1261. (e) Sharp, M. J.; Snieckus, V. Tetrahedron Letr. 1985, 26, 5997. ( 1 3) For reviews concerning the selective hydroboration, see: (a) Brown, H. C. Organic Synrhesis cia Boranes; Wiley: New York, 1975. (b) Cragg, G. M . L. Organobornnes in Organic Synrhesis; Marcel Dekker: New York, 1973. (c) Lane, C. F. Synthetic Reagents; Pizey, J. S., Ed.; Ellis Harwood: New York, 1977: Vol. 3 . (d) Mikhailov, Yu. N. Organoboron Compounds in Organic Synthesis; OPA: Amsterdam, 1984, (f) Suzuki, A,; Dhillon, R. S. Topics in Current Chemistry; Springer-Verlag: Berlin, 1986; Vol. 130, p 23. (14) Uenishi, J.; Beau, J-M.; Armstrong, R. W.: Kishi, Y. J . A m . Chem. SOC.1987, 109, 4156.
1
o c t y l - B ~
2 3
octyl-B(Sia),
4
(octyl),B
5
octyl-B!]
6
(2-butyl),B
7
3-
8
O
o
c
t
y
l
-
99
B
~
~
~
2
82 93
98 1
0
40' 65' 5 5.
B
___--
octylborane participated in the coupling (entry 4), and the leaving ability of the primary alkyl on the boron atom was shown to be higher than that of a secondary alkyl group. Under all the reaction conditions examined, none of the coupling products with secondary alkyls were detected in the crude reaction mixture (entries 1-3). 2-Octyl- 1,3-dioxaborinane was almost inactive under the conditions indicated (entry 5 ) . Entries 6-8 demonstrate that the coupling between secondary alkylboron compounds and iodobenzene can occur in moderate yields by using 3 M KOH in water as a base. Lower yields in the coupling of secondary alkyls may not be due t o p-elimination, but rather to the slow rate of transmetalation of secondary alkylboranes to PhPdI. Indeed, the yields of n-butylbenzene and benzene derived from p-elimination were less than 1% in the coupling of tri-2-butylborane (entry 6), whereas 1C-30% biphenyl, arising from homo-coupling, was obtained (entries 6-8). Although we have not studied the reaction mechanism in detail, the synthetic study described above has been carried out on the assumption that the desired coupling reaction of alkylboranes may proceed by a pathway similar to that of palladium-catalyzed cross-coupling reactions of organometallics2-'0 which involves (a) oxidative addition, (b) transmetalation, and (c) reductive elimination (eq 3). Due to the low nucleophilicity of alkylboranes, the transmetalation may be the rate-determining stepis among these three steps. It has been reported t h a t the addition of sodium hydroxide exerts a remarkable effect on the reaction of alkylboranes with mercuric,16 silver,17 auric,'7b and p l a t i n i ~ "halides. ~ It is also known that some of the M-OR reagents, such as Hg( O A C ) ~ ,Hg(OR)2,16d'e '~ and Ago,'' undergo the transmetalation reaction with alkylboranes in the absence of bases. Our preliminary experiments indicated that trioctylborane ( I equiv) reacts with P ~ ( O A Cin) ~refluxing benzene by forming metallic palladium to give octane (59%) and octene (3%), whereas no reactions were observed with PdC12, PdCI2(PPh3),, and PhPd(PPh,),I under such neutral conditions. T h e results suggested t h a t the r a t e of transmetalation is highly dependent on the ligands on the palladium (11) complexes, as observed in our previous study1Ia on the cross-coupling reaction of 1-alkenylboron compounds. On the other hand, lithium tetraalkylborates, which led to unsatisfactory results in the case of l-alkenyltrialkylb~rates,~'~~'~ brought about a clean coupling reaction. For instance, the reaction of the a t e (1 5 ) Negishi, E.; Takahashi, T.; Baba, S.; Van Horn, D. E.; Okukado, N. J . A m . Chem. SOC.1987, 109, 2393. (16) (a) Honeycutt, J . B.; Riddle, J. M. J . A m . Chem. SOC.1959,81, 2593. (b) Honeycutt, J. B.; Riddle, J. M. Ibid. 1960, 82, 3051. (c) Larock, R. C.; Brown, H. C. Ibid. 1970, 92, 2467. (d) Larock, R. C. J . Organomer. Chem. 1974, 67, 353. (e) Larock, R. C. (bid. 1974, 72, 35. (17) (a) Snyder, H. R.; Kuck, J. A,; Johnson, J. R. J . A m . Chem. SOC. 1938, 60, 105. (b) Brown, H. C.; Hebert, N. C.; Snyder, C. H. Ibid. 1961, 83. 1001. (c) Brown. H. C.; Snyder, H. C. Ibid. 1961, 83, 1002.
316 J . Am. Chem. SOC.,Vol. 1 1 1 , No. 1, 1989
Miyaura et al.
Table 111. Cross-Coupling Reaction of 9-Alkvl-9-BBN with Haloarenes (Ea 6 ) 7% yielda
entry
haloarene
alkene
product
procedure Ab
Cb
Bb
1-octene
1-octene
CH2=C
jH3 'CK3
CH,=CH(CH,),CO,Me CH,=CH(CH,),CN
CH,=CH(CH,),CO,Me
"GLC yields are based on the haloalkenes employed, and the isolated yields are in parentheses. b9-Alkyl-9-BBN was prepared by the usual method from alkene (1.1 equiv) and 9-BBN (1.1 equiv). The coupling reaction with haloarene (1 equiv) was conducted under the following conditions. Procedure A: PdCl,(dppf) (3 mol 5%) and NaOH (3 equiv) in T H F at 65 OC. Procedure B: PdCl,(dppf) (3 mol %), NaOMe (1.5 equiv) in 30% yield of 7-(4-acetylphenyl)-2T H F at 65 OC. Procedure C: PdCl,(dppf) (3 mol%) and K2C03 (2 equiv) in DMF-THF at 50 OC. methylheptane-1,2-diol was also obtained. Table IV. Cross-Coupling Reaction of 9-Alkyl-9-BBN with I-Halo-1-alkenes (Eq 7) entry
haloalkene
alkene
5% vield" procedure Ab
product
1
I-octene
85 ( X = Br),C70 (X = 1)'
2
1-octene
90d
3
1 -octene
94
4
CH2=CH(CH,),CO2Me
5
I-octene
Cb
Db
82'
69 98
6
7
8
9
10
4
Me02C
&
85
A ( CH2) IOCN
"GLC yields are based on the haloalkenes employed, and the isolated yields are in parentheses. bThe 9-alkyl-9-BBN obtained by hydroboration of alkene (1.1 equiv) with 9-BBN (1.1 equiv) was directly used for the next coupling reaction with 1-halo-1-alkene ( 1 equiv). Procedure A: PdCI*(dppf) (3 mol %) and NaOH (3 equiv) in T H F at 65 "C. Procedure C: PdCl,(dppf) (3 mol %) and K2C0, (2 equiv) in DMF-THF at 50 OC. Procedure D: PdCI2(dppf) (3 mol %) and K3P04 (1 equiv) in DMF-THF at 50 OC. '&Halostyrene ( E / Z = 99/1) gave decenylbenzene ( E / Z = 99/1). d/3-Bromostyrene ( E / Z = 1/99) gave decenylbenzene ( E / Z = 3/97).
J . Am. Chem. Soc., Vol. 111, No. I , 1989 317
Cross-Coupling Reactions of B-Alkyl-9- BBN Dericatives complex, obtained from B-octyl-9-BBN and 1 equiv of BuLi, with iodobenzene in refluxing T H F in the presence of 3 mol % of PdCl,(dppf) was complete in 5 h to give octylbenzene (50%) and butylbenzene (30%). On the basis of these results, the role of bases can be attributed to the increase in t h e nucleophilicity of alkylboranes by their coordination with the boron atoms, thereby facilitating the transfer of the alkyl group from boron to palladium to make complexes 2 (eq 3 and 4 ) . Although it is not clear a t present whether the R'
with B-alkyl-9-BBN having an epoxy group (entry 6 in Table HI), the expected coupling product was obtained in only 52% yield, contaminated with a 30% yield of 7-(4-acetylphenyl)-2-methylheptane-1,2-diol, which was formed as a result of the epoxide ring opening with K 2 C 0 3 . The usefulness of the present method was demonstrated by the synthesis of 1,Salkadienes and the extension of a side chain in a steroid (eq 8-11). Although the coupling reaction of two
R'
.^
5
(3)
X
R
1
2
6
(4)
I 0R '
or R-B
