Synthesis of pinacol allylic boronic esters via olefin cross-metathesis between pinacol allylboronate and terminal or internal alkenes

Article abstract of DOI:10.1055/s-2002-19356

The ruthenium-catalyzed olefin cross-metathesis between pinacol allylboronate, CH₂=CHCH₂B(O₂C₂Me₄), and RCH=CH₂ giving RCH=CHCH₂B(O₂C₂Me₄) was carried out in refluxing CH₂Cl₂ in the presence of an alkylidene-ruthenium complex (3 mol%).

Full text of DOI:10.1055/s-2002-19356

128
LETTER
Synthesis of Pinacol Allylic Boronic Esters via Olefin Cross-Metathesis
between Pinacol Allylboronate and Terminal or Internal Alkenes
S
ynthesis of Pinac
a
ol
A
llylic
B
s
oronic Es
u
ters via
O
lef
n
inCross-Met
o
athesis ri Yamamoto, Miki Takahashi, Norio Miyaura*
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Fax +81(11)7066561; E-mail: miyaura@org-mc.eng.hokudai.ac.jp
Received 10 October 2001
Abstract: The ruthenium-catalyzed olefin cross-metathesis be-
tween pinacol allylboronate, CH2=CHCH2B(O2C2Me4), and
RCH=CH2 giving RCH=CHCH2B(O2C2Me4) was carried out in re-
fluxing CH2Cl2 in the presence of an alkylidene-ruthenium complex
(3 mol%).
R
R
Bpin
5
6
3 or 4
(3 mol%)
1
pinB
+
Bpin
CH2Cl2, reflux
Key words: allylboron, olefin cross-metathesis, ruthenium catalyst
Bpin
O
Bpin = -B
O
R
2
R
7
Reactions of allylboranes with aldehydes or ketones have
proved to be very efficient for diastereoselective building
of several adjacent chiral centers.1 Allylboronic esters can
be best synthesized by transmetalation between an allyl-
magnesium or -lithium reagent and (RO)3B.2 A more gen-
eral approach including synthesis of chiral allylboronates
is to add an isomerically pure alkenylmetal to a ( -ha-
loalkyl)boronic ester.3 These methods utilizing lithium or
magnesium reagents are convenient for unfunctionalized
derivatives, but they are limited by the lack of compatibil-
ity with functional groups. Herein, we report an alterna-
tive method for the synthesis of allylic boronic esters via
olefin cross-metathesis4–6 between a pinacol allylboronate
2 and a terminal or internal alkene (Scheme 1). Grubbs
alkylidene-ruthenium complexes 3, 4 in refluxing CH2Cl2
provided variously functionalized allylboronic esters 5 in
high yields. Although the metathesis reaction has been
used much less frequently for the preparation of orga-
noboron compounds, synthesis of cyclic alkenylboronates
via ring-closing metathesis has recently been demonstrat-
ed by Renaud and Ouellet.7
N
N
Mes
Cl
Cl
PCy3
Mes
Ph
PhCHO
Cl
Cl
Ru
PCy3
3
Ru
PCy3
Ph
OH
OH
4
+
Ph
Ph
R
R
9
8
Scheme 1 Olefin cross-metathesis for synthesis of allylboronates 5
2,2-dimethyl-1,3-propanediol ester or 1,2-ethanediol es-
ter.
The reaction of 2 with a stoichiometric amount of styrene
giving the desired cross-metathesis product 5 (R = Ph,
40%) was accompanied by the formation of two ho-
modimerization products 6 (20%) and 7 (R = Ph, trace).
The product ratio was highly depended on the stoichiom-
etry of added styrene. For example, homodimerization of
2 afforded a high yield of 6 (85%), whereas it was very
slow for styrene (7: R = Ph, 37%). Thus, all reactions were
carried out in the presence of a large excess of alkene, typ-
ically 2 equivalents of a terminal or internal alkene, to
minimize the formation of 6. Under these conditions, pi-
nacol cinnamylboronate 5 (R = Ph) was selectively pro-
duced and was easily isolated by Kugelrohr distillation in
vacuo (74%, E/Z = 91/9); however, selective synthesis of
5 can be more difficult for aliphatic derivatives because
the reactivity of aliphatic alkenes is comparable to that
of 2.
Pinacol allylboronate 2 in CH2Cl2 was treated with an alk-
ene (1, 2 equiv) in the presence of an alkylidene-rutheni-
um complex (3 or 4, 3 mol%). After being refluxed for 24
h, the reaction mixture was directly treated with benzalde-
hyde (2 equiv) to quantitatively convert pinacol allylbor-
onate 5 to homoallyl alcohol 8/9. The reaction was run in
a flask equipped with an oil bubbler at the top of a con-
denser and at the reflux temperature of CH2Cl2. The slow
bubbling of argon into the CH2Cl2 solution to release eth-
ylene generated by the metathesis or the reaction in ben-
zene or 1,2-dichloroethane resulted in significantly low
yields. Pinacol can be the best protecting group of allylbo-
ronic acid since the reaction failed for the corresponding
Due to the difficulty in isolating pure 5 in small-scale
runs, the reaction mixture was directly trapped with ben-
zaldehyde; however, the formation of 5 and their cis/trans
ratios can be estimated from the yields and the diastereo-
meric ratios of 8/9. In situ treatment of the reaction mix-
ture of 2 and styrene, or the isolated 5 (R = Ph, E/Z = 90/
10), with benzaldehyde at room temperature overnight af-
Synlett 2002, No. 1, 28 12 2001. Article Identifier:
1437-2096,E;2002,0,01,0128,0130,ftx,en;Y21001ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Synthesis of Pinacol Allylic Boronic Esters via Olefin Cross-Metathesis
129
forded 1,2-diphenyl-3-butenol 8/9 (R = Ph, 91/9). Thus, to increase (E)-selectivity and to reduce homodimeriza-
the correlation between the E/Z ratio of 5 and anti/syn se- tion to 1,2-diarylethene. On the other hand, all attempts at
lectivity (8/9) was consistent with the previous findings metathesis of 2 with acrylonitrile, ethyl acrylate, or phenyl
that E-5 affords 8 and Z-5 yields 9 in allylboration of aro- vinyl ether failed.
matic and aliphatic aldehydes.3c
The results of the olefin cross-metathesis between 2 and
representative alkenes are summarized in Table. Aliphatic
O
R'
H
[Ru]
B
and terminal alkenes afforded the corresponding homoal-
lyl alcohols in 49–94% yields with 52–96% anti-selectiv-
ities (entries 1–7). Among them, methyl 3-butenoate
exhibited an exceptionally high anti-selectivity (anti/syn
= 96/4), thus suggesting a predominant formation of the
E-allylboronic ester (entry 6), which is in striking contrast
to the corresponding molybdenum-catalyzed reaction of
allyltrimethylsilane5 or allyltributylstanane6 that resulted
in a mixture of cis- and trans-isomers. Such an effect of a
neighboring group can be best explained by chelation of a
carbonyl oxygen to the ruthenium metal center (10), as
was suggested to occur in analogous metathesis reactions
of unsaturated amides (11 and 12)8,9 (Scheme 2). Internal
alkenes such as (E)- and (Z)-4-octene afforded compara-
ble yields and selectivities to those of terminal alkenes
(entries 8 and 9). The ruthenium catalyst 4 was used for
the methallyl ester due to inefficiency of 3 for such 1,1-
disubstituted alkenes (entry 10). High yields and high di-
astereoselectivities exceeding 90% were commonly
achieved for styrene and its para-substituted derivatives
(entries 11–13). The bulkiness of the aryl ring may serve
O
O
[Ru]
[Ru]
O
H
R2N
NR2
O
OMe
10
11
12
Scheme 2 Chelation effect
Finally, the utility of the protocol was demonstrated in the
synthesis and reaction of a chiral allylboration reagent 14
(Scheme 3). Under conditions analogous to those used for
the pinacol ester, cross-metathesis between tartrate ester
13 and methyl 3-butenoate was completed within 24 h.
Allylboration of aldehydes at –78 °C for 5 h was followed
by acid-catalyzed lactonization to provide 16a–c (syn/anti
= 96/4). Although the enantioselectivities depended great-
ly upon the aldehydes employed, the reaction with 3-me-
thyl-2-butenal achieved 82% ee.10
i
CO2 Pr
CH2=CHCH2CO2Me
O
B
i
CO2 Pr
Table Synthesis of Pinacol Allylic Boronates via Cross-Metathesis
between 2 and Terminal or Internal Alkenesa
4 (3 mol%), CH2Cl2, 40 °C, 24 h
O
13
OH
i
CO2 Pr
Entry
1
Alkene
Yield/%b
62
anti/syn (8/9)
75/25
52/48
78/22
69/31
67/33
96/4
O
B
RCHO
R
i
CO2 Pr
1-octene
-78 °C
5 h
O
MeO2C
CO2Me
15a-c
2
PhCH2CH=CH2
BrCH2CH2CH=CH2
BrCH2CH2CH2CH=CH2
PhOCH2CH=CH2
MeO2CCH2CH=CH2
MeCO2CH2CH=CH2
(E)-4-octene
55
14
R
3
69
H+
16a: R=Ph
16b: R=cyclo-C6H11 60%, 65%ee
16c: R= Me2C=CH 78%, 82%ee
30%, 49%ee
4
71
O
5
79
O
6
94
Scheme 3 Synthesis of chiral allylboronates
7
67
63/36
78/22
73/27
81/19
91/9
Representative procedure:
8
55
A 25 mL flask, connected through the condenser to a nitrogen
source and an oil bubbler, was charged with a ruthenium catalyst (3,
0.03 mmol) and flushed with argon. Dry dichloromethane (5 mL),
styrene (2 mmol), and pinacol allylboronate (2, 1 mmol) were added
successively. After being refluxed for 24 h, benzaldehyde (2 mmol)
was added and the mixture was then stirred at room temperature
overnight. The product was extracted with ether, washed with brine,
dried over MgSO4, and finally chromatographed over silica gel with
hexane–ether (2/1). 8 (R = Ph): 1H NMR (400 MHz, CDCl3) 7.04–
7.38 (m, 10 H), 6.25 (ddd, 1 H, J = 17.1, 10.2 and 8.9 Hz), 5.27 (d,
1 H, J = 10.2 Hz), 5.23 (d, 1 H, J = 17.1 Hz), 4.85 (dd, 1 H, J = 7.8
and 2.4 Hz), 3.55 (dd, 1 H, J = 8.3 and 8.3 Hz), 2.30 (d, 1 H, J = 2.7
Hz); minor signals of 9 appeared at 5.90 (ddd, 1 H, J = 17.2, 10.3
and 7.8 Hz), 4.91 (d, 1 H, J = 8.3 Hz), 3.64 (dd, 1 H, J = 8.1 and 8.1
Hz).
9
(Z)-4-octene
57
10c
11
12
13
PhCO2CH2C(CH3)=CH2
PhCH=CH2
49
88
4-MeOC6H4CH=CH2
4-ClC6H4CH=CH2
87
91/9
76
90/10
a A mixture of pinacol allylboronate (2, 1 mmol), alkene (2 mmol) in
CH2Cl2 was refluxed for 24 h in the presence of a ruthenium catalyst
(3, 3 mol%). The reaction mixture was then treated with PhCHO (2
mmol) at room temperature for 24 h, unless otherwise noted.
b Isolated yields.
c Ruthenium catalyst (4, 3 mol%) was used.
Synlett 2002, No. 1, 128–130 ISSN 0936-5214 © Thieme Stuttgart · New York

130
Y. Yamamoto et al.
LETTER
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(10) 16c: HPLC on Chiralcel OB-H (Dicel Co., Ltd) with
25
hexane–2-propanol (99.5:0.5) showed 82% ee; [ ]D
=
+37.5 (c 1.02, CHCl3); 1H NMR (400 MHz, CDCl3) 5.73
(ddd, 1 H, J = 17.1, 10.2 and 8.3 Hz), 5.11–5.29 (m, 4 H),
3.24 (dddd, 1 H, J = 7.6 Hz), 2.69 (dd, 1 H, J = 17.3 and 8.0
Hz), 2.50 (dd, 1 H, J = 17.3 and 7.6 Hz), 1.78 (s, 1 H), 1.71
(s, 1 H). Two percent of NOE was observed between two
hydrogens at the carbon atoms attached to ethenyl and 2-
methyl-1-propenyl group; 13C NMR (100 MHz, CDCl3)
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176.2; exact mass calcd for C10H14O2 166.0994, found
166.0992.
Synlett 2002, No. 1, 128–130 ISSN 0936-5214 © Thieme Stuttgart · New York