Nickel-catalyzed borylation of aryl cyclopropyl ketones with bis(pinacolato)diboron to synthesize 4-oxoalkylboronates

Article abstract of DOI:10.1021/jo900071m

Aryl cyclopropyl ketones undergo nickel-catalyzed borylative ring opening with bis(pinacolato)diboron to yield 4-oxoalkylboronates.

Full text of DOI:10.1021/jo900071m

TABLE 1. Optimization of Reaction Conditions
Nickel-Catalyzed Borylation of Aryl Cyclopropyl
Ketones with Bis(pinacolato)diboron to
Synthesize 4-Oxoalkylboronates
Yuto Sumida, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Kyoto-daigaku Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
yori@orgrxn.mbox.media.kyoto-u.ac.jp;
oshima@orgrxn.mbox.media.kyoto-u.ac.jp
entry
catalyst (mol %)
ligand (mol %)
base
yield (%)a
1
2
3
4
5
6
7
8
9
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (10)
Ni(cod)2 (5)
PCy3 (20)
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
MeOK
MeOK
47
18
30
PtBu3 (20)
ReceiVed January 13, 2009
IPr ·HCl (12)
IMes ·HCl (12)
PCy3 (20)
IMes ·HCl (12)
IMes ·HCl (12)
IMes ·HCl (12)
IMes ·HCl (6)
49
33b
27b
77c
88c
92c d
,
a NMR yields. b Toluene/MeOH (30/1) and 1.5 equiv of diboron were
used. c Toluene/MeOH (15/1) and 1.5 equiv of diboron were used. d At
50 °C and isolated yield.
Aryl cyclopropyl ketones undergo nickel-catalyzed borylative
ring opening with bis(pinacolato)diboron to yield 4-oxoalkylbo-
ronates.
According to our previous reports,9 we first attempted the
borylative ring-opening reaction by using the previous standard
conditions. However, the attempt failed to attain high yield.
Specifically, treatment of cyclopropyl phenyl ketone (1a) with
bis(pinacolato)diboron (2) in the presence of a nickel/tricyclo-
hexylphosphine catalyst, sodium hydroxide, and H2O in toluene/
MeOH afforded the corresponding 4-oxoalkylboronate 3a in
47% yield (Table 1, entry 1). Tri-tert-butylphosphine was
inferior to tricyclohexylphosphine (entry 2). When we applied
N-heterocyclic carbene ligands to this reaction, the results were
improved. Among the carbene ligands, IMes ·HCl11 showed the
highest activity (entry 4). Interestingly, palladium catalysis also
effected the ring-opening reaction, albeit in lower yields (entries
5 and 6).
Organoboron compounds are extremely important reagents
in organic synthesis.1 Transition metal-catalyzed borylation of
unsaturated C-C bonds is one of the most powerful methods
to synthesize organoboron reagents.2 Although many examples
of borylation of unsaturated C-C bonds catalyzed by Pt,3 Pd,4
Rh,5 Cu,6 and Au7 are known, there are few examples of bo-
rylation catalyzed by nickel complexes.8
Recently, we reported nickel-catalyzed ꢀ-borylation of R,ꢀ-
unsaturated esters and amides and the borylative ring-opening
reaction of vinylcyclopropanes.9 In the course of these studies,
we found another borylative reaction. Here we report nickel-
catalyzed borylative ring-opening reactions of aryl cyclopropyl
ketones with bis(pinacolato)diboron yielding synthetically useful
4-oxoalkylboronates.10
A higher concentration and an increased amount of diboron
enhanced the reaction (entry 7, 77% yield). To optimize this
transformation, we next investigated the effects of the bases.
After extensive investigations, we found that metal alkoxides
were effective. Thus, a high yield was observed with potassium
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2483. (c) Davison, M.; Hughes, A. K.; Marder, T. B.; Wade, K. Contemporary
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3196 J. Org. Chem. 2009, 74, 3196–3198
10.1021/jo900071m CCC: $40.75 2009 American Chemical Society
Published on Web 03/11/2009

TABLE 2. Scope of Cyclopropyl Ketones
SCHEME 1. Reaction of Disubstituted Cyclopropanes
entry
Ar
product
temp (°C)
yield (%)a
1
2
3
4
5
6
4-MeC6H4 (1b)
4-MeOC6H4 (1c)
4-FC6H4 (1d)
2-naphthyl (1e)
2-furyl (1f)
3b
3c
3d
3e
3f
50
40
50
50
40
70
79
88
79
95
54b
16b c
,
2-MeC6H4 (1g)
3g
a Isolated yields. b 10 mol % of Ni(cod)2 and 12 mol % of IMes ·HCl
were used. c NMR yields.
SCHEME 2. Plausible Mechanism
methoxide (entry 8). Moreover, the reaction proceeded smoothly
at 50 °C and gave product 3a in 92% isolated yield, even if an
amount of the catalyst was reduced to 5 mol % (entry 9).12
Having optimum conditions in hand, a borylative opening
reaction was carried out with various aryl cyclopropyl ketones.
The reactions of 1b and 1c with 2 gave 3b and 3c in 79% and
88% yields, respectively (Table 2, entries 1 and 2). The
borylation reaction of 1c required a slightly lower temperature
since 3c was unstable at 50 °C or higher. Fluorine-containing
1d and 2-naphthyl ketone 1e were converted to the desired
products 3d and 3e in 79% and 95% yields, respectively (entries
3 and 4). In addition, heterocyclic compound 1f can be employed
to afford 3f in moderate yield (entry 5). Probably because the
methyl group of 1g blocks interaction between 1g and active
nickel species, the reaction of 1g was sluggish to afford 3g in
only 16% yield (entry 6). Unfortunately, the product was not
obtained with alkyl cyclopropyl ketones under this catalytic
system (vide infra).
We also investigated the borylative reaction of aryl cyclo-
propyl ketones having an additional substituent on the cyclo-
propane ring. There are two C-C bonds that may be cleaved
in 1,2-disubstituted cyclopropyl ketones 1h and 1i. Fortunately,
the reactions of trans-1-benzoyl-2-phenylcyclopropane (1h) and
trans-1-benzoyl-2-methylcyclopropane (1i) led to 3h and 3i as
sole products in 79% and 59% yields, respectively (Scheme 1,
eqs 1 and 2). It showed that the cleavage of the C-C bond
took place selectively on the less sterically hindered side.
Furthermore, 1-methylcyclopropyl phenyl ketone (1j) also
underwent this transformation in high yield (Scheme 1, eq 3).
On the basis of our studies on nickel-catalyzed borylation,9
we assume the reaction mechanism as follows (Scheme 2).
Formation of oxanickelacycle intermediate 4 would occur by
oxidative cyclization of cyclopropyl ketone to nickel(0), which
was reported by the groups of Ogoshi and Kurosawa13 and
Montgomery.14 In this step, Lewis acidic bis(pinacolato)diboron
might activate the cyclopropyl ketone and promote oxidative
cyclization. Transmetalation would then take place to give
alkylnickel intermediate 5 bearing a boron enolate moiety (path
A). Reductive elimination produces the boron enolate of 3a,
which is protonated in situ to afford 3a, with regeneration of
the initial nickel(0) complex. The reaction required base, which
would activate the boron species.15 The roles of MeOH and
H2O are not clear at this point according to this mechanisim.16
Another mechanism (path B) that involves a formation of
alkoxynickel intermediate 6 by protonolysis of 4 with MeOH
may operate.17 In this mechanism, transmetalation between 6
and diboron 2 easily occurred to provide alkylnickel intermediate
5′ (path B).18
In the cases of alkyl cyclopropyl ketones, oxidative cyclization
to nickel(0) would be sluggish, because alkyl cyclopropyl
ketones are electron rich compared to aryl cyclopropyl ketones.
Furthermore, oxanickelacycle generated from alkyl cyclopropyl
ketone with nickel(0) would be less stable than that generated
from aryl cyclopropyl ketones.
Finally, we subjected 4-oxoalkylboronates to the Suzuki-
Miyaura cross coupling reaction (Scheme 3). After conversion
of 3a to trifluoroborate 3k in 92% yield, 3k reacted with
4-bromoanisole in the presence of 5 mol % of Pd(OAc)2, 10
mol % of RuPhos (2-dicyclohexylphosphino-2′,6′-diisopropoxy-
(9) (a) Hirano, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9, 5031–
5033. (b) Sumida, Y.; Yorimitsu, H.; Oshima, K. Org. Lett. 2008, 10, 4677–
4679.
(10) (a) Knochel, P. J. Am. Chem. Soc. 1990, 112, 7431–7433. (b) Molander,
G. A.; Bobbitt, K. L.; Murray, C. K. J. Am. Chem. Soc. 1992, 114, 2759–2760.
(c) Pereira, S.; Srebnik, M. Tetrahedron Lett. 1995, 36, 1805–1808. (d) Lopez-
Ruiz, H.; Zard, S. Z. Chem. Commun. 2001, 2618–2619.
(11) (a) Arduengo, A. J., III.; Krafczyk, R.; Schmutzler, R.; Craig, H. A.;
Goerlich, J. R.; Marshall, W. J.; Unverzagt, M. Tetrahedron 1999, 55, 14523–
14534. (b) Jafarpour, L.; Stevens, E. D.; Nolan, S. P. J. Organomet. Chem. 2000,
606, 49–54.
(14) Liu, L.; Montgomery, J. J. Am. Chem. Soc. 2006, 128, 5348–5349.
(15) When only 10 mol % of MeOK was used to generate carbene ligand,
an 11% NMR yield of 3a was observed.
(16) When MeOH was not used, the yield of 3a was only 33% (NMR yield).
(17) Mannathan, S.; Jeganmohan, M.; Cheng, C.-H. Angew. Chem., Int. Ed.
2009, 48, 2192–2195.
(12) A 78% isolated yield of 3a was obtained in larger scale (5 mmol of 1a).
(13) Ogoshi, S.; Nagata, M.; Kurosawa, H. J. Am. Chem. Soc. 2006, 128,
5350–5351.
(18) (a) Dible, B. R.; Sigman, M. S.; Arif, A. M. Inorg. Chem. 2005, 44,
3774–3776. (b) Lee, C. H.; Laitar, D. S.; Mueller, P.; Sadighi, J. P. J. Am. Chem.
Soc. 2007, 129, 13802–13803.
J. Org. Chem. Vol. 74, No. 8, 2009 3197

SCHEME 3. Application of 3a to Suzuki-Miyaura Cross
Coupling
In summary, we have developed a new borylation reaction
under nickel catalysis by using aryl cyclopropyl ketones as
substrates, which allows the synthesis of functionalized alkyl-
boronates for synthetic use.
Experimental Section
Typical Procedure for Borylative Ring Opening. Ni(cod)2 (2.8
mg, 0.010 mmol), IMes ·HCl (8.2 mg, 0.012 mmol), and MeOK
(28 mg, 0.4 mmol) were placed in a 20-mL reaction flask under
argon. After toluene (0.5 mL) was added, the resulting suspension
was stirred for 10 min at room temperature. Cyclopropyl ketone
1a (29 mg, 0.20 mmol) and bis(pinacolato)diboron (2, 76 mg, 0.30
mmol) in toluene (1.0 mL) were then added. Methanol (0.10 mL)
and H2O (10 µL) were added, and the mixture was allowed to warm
to 50 °C and stirred for 5 h. The reaction mixture was filtered by
alumina (Wako, activated), followed by concentration in vacuo to
afford an oil. The crude oil was purified on silica gel (Kanto
Chemical, silica gel 60N, hexane/ethyl acetate ) 5:1) by using a
dry ice/acetone-jacketed chromatographic column to yield 3a (51
mg, 0.18 mmol) in 92% yield.
SCHEME 4. Diastereoselective Reduction of 3h
1-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-bu-
tanone (3a): IR (neat) 2978, 2935, 1684, 1373, 1317, 1145, 691
cm-1; 1H NMR (CDCl3) δ 0.89 (t, J ) 8.0 Hz, 2H), 1.25 (s, 12H),
1.86 (tt, J ) 8.0, 7.5 Hz, 2H), 2.98 (t, J ) 7.5 Hz, 2H), 7.45 (dd,
J ) 8.0, 7.5 Hz, 2H), 7.54 (dd, J ) 8.0, 7.5 Hz, 1H), 7.97 (dd, J
) 8.0, 7.5 Hz, 2H); 13C NMR (CDCl3) δ 19.3, 24.8, 40.9, 83.1,
128.1, 128.5, 132.8, 137.1, 200.6. The signal for the carbon that is
attached to the boron atom was not observed. Found: C, 70.19; H,
8.65. Calcd for C16H23O3B: C, 70.09; H, 8.45.
1,1′-biphenyl), and K2CO3 in toluene/H2O at 80 °C19 to provide
the corresponding product 7 in 74% yield.
Molander et al. developed highly diastereoselective reduction
of 2-substituted-4-oxoalkylboronates, wherein intramolecular
coordination of the carbonyl oxygen to the boronate ester plays
a key role.10b The procedure was applicable to the reduction of
3h. Treatment of boronate 3h with BH3 ·THF as a reductant
followed by oxidation and esterification afforded the corre-
sponding diester 8 in 74% yield with good diastereoselectivity
(Scheme 4).
Acknowledgment. This work was supported by Grants-in-
Aid for Scientific Research and Global COE Research Programs
from JSPS.
Supporting Information Available: NMR spectra of prod-
ucts. This material is available free of charge via the Internet at
http://pubs.acs.org.
(19) Molander, G. A.; Petrillo, D. E. Org. Lett. 2008, 10, 1795–1798.
JO900071M
3198 J. Org. Chem. Vol. 74, No. 8, 2009