Rhodium-catalyzed asymmetric conjugate addition of arylboroxines to borylalkenes: Asymmetric synthesis of β-arylalkylboranes

Article abstract of DOI:10.1002/anie.201004980

Asymmetric conjugate addition of arylboroxines to borylalkenes proceed in the presence of a chiral bisphosphine/rhodium complex as a catalyst to give chiral β-arylalkylboranes with high enantioselectivities (see scheme). [O]=H₂O₂/NaOH.

Full text of DOI:10.1002/anie.201004980

Angewandte
Chemie
DOI: 10.1002/anie.201004980
Rhodium Catalysis
Rhodium-Catalyzed Asymmetric Conjugate Addition of
Arylboroxines to Borylalkenes: Asymmetric Synthesis of
b-Arylalkylboranes**
Keigo Sasaki and Tamio Hayashi*
The transition-metal-catalyzed asymmetric conjugate addi-
tion of organometallic reagents to electron-deficient olefins
examined 4-phenyl-1-butenylboronic acid (1a) for the addi-
tion of phenylboroxine (5m, 3 equiv B) in the presence of
À
provides a powerful tool for carbon carbon bond formation
[{Rh(OH)((R)-binap)}2] as a catalyst (5 mol% Rh) in diox-
ane/H2O (10:1) at 608C for 18 hours (Table 1), which is one of
our sets of standard reaction conditions for the rhodium-
catalyzed asymmetric addition reactions.[13] The crude reac-
tion mixture was subjected to oxidation with H2O2 and NaOH
with the simultaneous introduction of a new stereogenic
carbon center at the b position,[1] and the use of chiral
rhodium catalysts for the asymmetric addition of arylboron
reagents has developed rapidly[2] since it was first reported in
1998 where the acceptors were b-substituted a,b-unsaturated
ketones.[3] This asymmetric catalysis by rhodium has been
successfully extended to the addition to olefins bearing
ester,[4] amide,[5] aldehyde,[6] phosphonate,[7] nitro,[8] and
sulfone[9] groups (Scheme 1). Herein, we wish to report that
olefins substituted with a boryl group are good substrates for
Table 1: Addition of phenylboron reagents to borylalkenes.[a]
Scheme 1. Rhodium-catalyzed asymmetric conjugate addition to
À
À
Ph BY2 (5)
carbon carbon double bonds.
Entry
BX2 in borylalkene
Yield [%][b]
1
2
3
4
5
6
7
8
B(OH)2 (1a)
B(pin) (2a)
B(mida) (3a)
B(dan) (4a)
B(dan) (4a)
B(dan) (4a)
B(dan) (4a)
B(dan) (4a)
(PhBO)3 (5m)
(PhBO)3 (5m)
(PhBO)3 (5m)
(PhBO)3 (5m)
PhB(OH)2
PhB(pin)
PhBF3K
Ph4BNa
4[c]
9[c]
0
77
75
26
0
the rhodium-catalyzed asymmetric addition reaction, thus
giving chiral b-arylalkylboranes with high enantioselectivities.
The high efficiency of the reaction was achieved by use of the
1,8-naphthalenediaminatoboryl group, B(dan), as a masking
group for alkenylboronic acids, which has recently been
developed by Suginome and co-workers.[10,11]
0
À
[a] Reaction conditions: borylalkene (0.20 mmol), Ph BY2 (0.60 mmol
B), catalyst (10 mmol Rh, 5 mol%), dioxane/H2O (10:1, 1.1 mL).
[b] Yield of isolated alcohol 6am. [c] 6-Phenyl-2-(2-phenylethyl)-3-hexenol
(7) was formed in 3% yield in both entries 1 and 2.
Considering that the rhodium-catalyzed conjugate addi-
tion has wide applicability for a variety of functionalized
[2]
À
carbon carbon multiple bonds and that alkenylboron
derivatives are reactive substrates, for example, as dieno-
philes in Diels–Alder reactions,[12] we anticipated that alke-
nylboron derivatives would be capable of being Michael
acceptors in the rhodium-catalyzed reactions. First, we
to give a 4% yield of 2,4-diphenyl-1-butanol (6am) as the
desired conjugate-addition product together with 3% yield of
6-phenyl-2-(2-phenylethyl)-3-hexenol (7), which resulted
from the homo addition of 1a (Table 1, entry 1). The low
yield of alcohols 6am and 7 is due in part to decomposition of
the alkylboronic acids, which are generated by cross and
homo addition, probably through transmetalation to rho-
dium(I) under the reaction conditions. In order to inhibit the
homo addition and the decomposition of the cross-addition
product, the alkenylboronic acid derivatives 2a–4a, which are
expected to be less reactive than 1a in the transmetalation to
rhodium(I), were examined under similar conditions. The
reaction of pinacol ester[14] 2a gave a slightly improved yield
of 6am, but mida boronate[15] 3a did not produce 6am
[*] K. Sasaki, Prof. Dr. T. Hayashi
Department of Chemistry, Graduate School of Science
Sakyo, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3988
E-mail: thayashi@kuchem.kyoto-u.ac.jp
[**] This work has been supported by a Grant-in-Aid for Scientific
Research (S) (19105002) from the MEXT (Japan). K.S. thanks the
JSPS for Young Scientists for a research fellowship. We thank
Takasago International Corporation for the gift of (R)-DTBM-
segphos.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201004980.
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(Table 1, entries 2 and 3). The use of RCH CHB(dan)[10] (4a)
greatly improved the selectivity giving the cross-addition
product 6am. Thus, the reaction of 4a with 5m gave, after
oxidation, 77% yield (based on 4a) of the alcohol 6am with
no formation of 7 (Table 1, entry 4). The use of PhB(OH)2 in
place of boroxine 5m gave a slightly lower yield of 6am
(Table 1, entry 5). PhB(pin) did not improve the yield of
alcohol 6am, and the addition was not observed at all with
PhBF3K[16] or Ph4BNa[17] (Table 1, entries 6–8).
catalyst from [Rh(acac)(C2H4)2] and (R)-binap provided
essentially the same result (Table 2, entry 6). The enantiose-
lectivity was a little higher (90% ee) with (R)-segphos[18] as a
ligand (Table 2, entry 7), and (R)-DTBM-segphos[18] showed
the highest selectivity (97% ee) although the yields are lower
because of incomplete conversion of starting 4a (Table 2,
entries 8 and 9). The absolute configuration of 6am was
determined to be R by comparison of its optical rotation with
the reported value.[19]
=
In the reaction of 4a with 5m, the conjugate-addition
product before oxidation was isolated as a pinacol borane 8 in
high yield by treatment of the crude reaction product with
pinacol under acidic conditions, and the oxidation of isolated
pinacol borane 8 gave a higher yield of alcohol 6am than the
direct oxidation of crude alkylB(dan). Thus, the rhodium-
catalyzed addition under the same conditions as in Table 1,
entry 4, followed by pinacol borane formation, gave 93%
yield of 8 and 87% yield of 6am (based on 4a; Table 2,
entry 1). The enantioselectivity of the present asymmetric
addition to alkenylB(dan) 4a is strongly dependent on the
solvent and chiral ligand employed (Table 2). Although the
yield was high in the reaction with [{Rh(OH)((R)-binap)}2] as
catalyst in dioxane/H2O, the enantiomeric purity was not
particularly high (77% ee; Table 2, entry 1). Of the alcohols
examined as solvent, tBuOH gave the best results (89% yield,
87% ee) with [{Rh(OH)((R)-binap)}2] as a catalyst (Table 2,
entries 2–5). The in situ generation of the Rh/(R)-binap
In addition to the oxidation into alcohol 6am, the pinacol
borane (R)-8 obtained here with high ee (97%) was readily
À
applied to C C bond-forming reactions by taking advantage
of the wide synthetic utility of alkylboronates (Scheme 2).
Scheme 2. Synthetic reactions of chiral alkylborane (R)-8.
Thus, for example, the alkyltrifluoroborate generated from 8
was subjected to the palladium-catalyzed cross-coupling
reaction under Molander conditions[20] to give a 66% yield
(based on 8) of (S)-9 without loss of enantiomeric purity. One-
carbon homologation with a lithium carbenoid according to
Mattesonꢀs protocol[21] followed by the oxidation gave alde-
hyde (S)-10 with the same ee.
Table 2: Asymmetric addition of phenylboroxine (5m) to alkenylborane
4a.[a]
Table 3 summarizes the results obtained for the asym-
metric addition of arylboroxines 5 to alkenylB(dan) 4. Aryl
groups (5n–5p) having electronically different substituents
were successfully introduced onto 4a to give, after oxidation,
the corresponding alcohols 6 with high enantioselectivity (93–
97% ee) using segphos or DTBM-segphos (Table 3, entries 2–
Entry Catalyst
Solvent
Yield [%][b] ee
[%][c]
=
4). Conjugate addition to RCH CHB(dan)ꢀs 4b–4d, which
1
[{Rh(OH)((R)-binap)}2]
dioxane/H2O
(10:1)
87
(93)[d]
50
37
61
89
84
82
56
77
possess other arylalkyl or alkyl substituents at the b position,
also proceeded with high selectivity to give the corresponding
alcohols 6bm, 6cm, and 6do with the selectivity around 90%
(entries 5–7).
In summary, we have described the development of a
rhodium-catalyzed asymmetric addition of arylboroxines to
borylalkenes giving b-arylated alkylboron compounds with
high enantioselectivity, which was realized by use of B(dan) as
a boryl group in the borylalkenes.
2
3
4
5
6
7
8
[{Rh(OH)((R)-binap)}2]
[{Rh(OH)((R)-binap)}2]
[{Rh(OH)((R)-binap)}2]
[{Rh(OH)((R)-binap)}2]
[Rh(acac)(C2H4)2]/(R)-binap
[Rh(acac)(C2H4)2]/(R)-segphos
[Rh(acac)(C2H4)2]/
(R)-DTBM-segphos
[Rh(acac)(C2H4)2]/
(R)-DTBM-segphos
MeOH
EtOH
iPrOH
tBuOH
tBuOH
tBuOH
tBuOH
89
81
72
87
87
90
97
9[e]
tBuOH
77
97
(82)[d]
[a] Reaction conditions: alkenylborane 4a (0.20 mmol), boroxine 5m
(0.20 mmol, 3 equiv of B), catalyst (10 mmol Rh, 5 mol%), solvent
(1.0 mL). [b] Yield of isolated alcohol 6am (based on 4a). [c] Determined
by HPLC analysis (Chiralpak AS-H) of 6am. [d] Yield of isolated
alkylboronic acid pinacol ester 8. [e] Reaction with 0.40 mmol of 5m
and 10 mol% of the catalyst for 40 h. binap=2,2’-bis(diphenylphos-
phanyl)-1,1’-binaphthyl.
Experimental Section
A solution of [Rh(acac)(C2H4)2] (5.2 mg, 20 mmol Rh, 10 mol% Rh)
and (R)-DTBM-segphos (25.9 mg, 22 mmol) in CH2Cl2 (0.50 mL) was
stirred at room temperature for 10 min. The solvent was removed
under vacuum, and 4-phenyl-1-butenylB(dan) (4a) (59.6 mg,
0.20 mmol), phenylboroxine (5m) (125 mg, 0.40 mmol, 1.2 mmol of
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Chemie
Table 3: Asymmetric addition to alkenylboranes 4.[a]
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Entry
R (4)
Ar (5)
Chiral ligand
Yield [%][b]
ee [%][c]
1[d]
2[d]
3
Ph(CH2)2 (4a)
Ph(CH2)2 (4a)
Ph(CH2)2 (4a)
Ph(CH2)2 (4a)
Ph(CH2)3 (4b)
PhCH2 (4c)
Ph (5m)
4-MeC6H4 (5n)
4-ClC6H4 (5o)
4-FC6H4 (5p)
Ph (5m)
(R)-DTBM-segphos
(R)-DTBM-segphos
(R)-segphos
(R)-segphos
(R)-DTBM-segphos
(R)-segphos
77 (6am)
74 (6an)
70 (6ao)
85 (6ap)
65 (6bm)
70 (6cm)
86 (6do)
97 (R)
97 (R)
94 (R)
93 (R)
95 (R)
93 (R)
87 (R)
4
5[d]
6
Ph (5m)
4-ClC6H4 (5o)
7
n-C5H11 (4d)
(R)-segphos
[a] Reaction conditions: alkenylborane 4 (0.20 mmol), boroxine 5 (0.20 mmol, 3 equiv B), [Rh(acac)-
(C2H4)2] (10 mmol, 5 mol%), chiral ligand (11 mmol), tBuOH (1.0 mL). [b] Yield of isolated alcohol 6.
[c] Determined by HPLC analysis. The absolute configuration R for 6am and 6 cm was determined from
their optical rotations, and that for other alcohols 6 was assigned by analogy of the stereochemical
pathway. [d] Reaction with 0.40 mmol of 5 and 10 mol% of the catalyst for 40 h.
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B), and tert-butyl alcohol (1.0 mL) were added successively. The
mixture was stirred at 608C for 40 h. The reaction mixture was
directly passed through a pad of silica gel with hexane/EtOAc (3:1)
and the solvent was removed under vacuum. 2m H2SO4 (1.0 mL) and
pinacol (118 mg, 1.0 mmol) were added to a solution of the crude
alkylB(dan) obtained above in tetrahydrofuran (2.0 mL). The mix-
ture was stirred at room temperature overnight, before it was diluted
with H2O and the aqueous layer was extracted with Et2O. The
combined organic layers were dried over MgSO4, filtered, and
concentrated under vacuum. The residue was subjected to column
chromatography on silica gel (hexane/EtOAc = 20:1) to give (R)-2,4-
diphenylbutylboronic acid pinacol ester (8; 55.1 mg, 82% yield,
97% ee).
[13] T. Hayashi, M. Takahashi, Y. Takaya, M. Ogasawara, J. Am.
Chem. Soc. 2002, 124, 5052. Binap: 2,2’-bis(diphenylphosphino)-
1,1’-binaphthyl.
Received: August 10, 2010
Published online: September 20, 2010
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Keywords: alkylboranes · asymmetric catalysis · borylalkenes ·
conjugate addition · rhodium
.
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