Diels-Alder reaction of 2,3-bis-(pinacolatoboryl)-l,3-butadiene: Facile preparation of 1,2-bis-(pinacolatoboryl)cyclohexenes and -1,4-cyclohexadiene

Article abstract of DOI:10.1246/bcsj.81.518

Diels-Alder reaction of 2,3-bis(pinacolato)boryl-l,3-butadiene with electron-deficient alkenes and dimethyl acetylenedicarboxylate proceeded smoothly upon heating, giving rise to the corresponding 1,2-diborylcyelohexenes in good to excellent yields. Conve

Full text of DOI:10.1246/bcsj.81.518

518 Short Articles
Bull. Chem. Soc. Jpn. Vol. 81, No. 4, 518–520 (2008)
Table 1. Diels–Alder Reaction of 1 with Various Dieno-
philesa)
Diels–Alder Reaction of 2,3-Bis-
(pinacolatoboryl)-1,3-butadiene:
Facile Preparation of 1,2-Bis-
(pinacolatoboryl)cyclohexenes
and -1,4-cyclohexadiene
Entry
Dienophile
2
T/ꢁC
(t/h)
Product 3
(Yield/%)
O
N
O
B
B
Ph
N
Ph
130
(1)
1
O
O
3a (95)
2a
ꢀ
Masaki Shimizu, Katsuhiro Shimono,
O
O
O
B
B
Takuya Kurahashi, Shin-ichi Kiyomoto,
Ikuhiro Nagao, and Tamejiro Hiyama
120
(3)
O
2
O
O
2b
3b (99)
Department of Material Chemistry, Graduate School of
Engineering, Kyoto University, Kyoto University Katsura,
Nishikyo-ku, Kyoto 615-8510
E
E
B
B
E
180
(4)
3c)
E
2c
3c (78)
Received November 12, 2007; E-mail: shimizu@npc05.kuic.
kyoto-u.ac.jp
B
B
E
E
140
(3)
4c)
E
E
Diels–Alder reaction of 2,3-bis(pinacolato)boryl-1,3-
butadiene with electron-deficient alkenes and dimethyl ace-
tylenedicarboxylate proceeded smoothly upon heating, giv-
ing rise to the corresponding 1,2-diborylcyclohexenes in
good to excellent yields. Conversion of two C–B bonds in
the cycloadducts into C–C bonds is also demonstrated.
2d
3d (87)
E
B
B
E
130
(2)
5c)
2e
3e (65)
O
O
H
Since a carbon–boron bond of alkenylboron compounds can
be converted stereospecifically into a carbon–carbon bond,1,2
both gem- and vic-diborylated olefins serve as versatile re-
agents for concise preparation of multi-substituted olefins.3
gem- and vic-Diborylated acyclic olefins are now readily avail-
able via diborylation with diborons of alkylidene-type carbe-
noids and alkynes, respectively.3 However, such method-
ologies cannot be applied to preparation of diborylated cyclo-
alkenes. Alternatively, cycloaddition reactions with boron-
containing building blocks constitute a promising approach
to boryl-substituted cyclic compounds that can serve as useful
precursors of polysubstituted cyclic compounds.4 We report
herein that the Diels–Alder reaction of 2,3-bis(pinacolato)-
boryl-1,3-butadiene (1)5 provides us with 1,2-diborylcyclohex-
enes 3 in good to excellent yields (eq 1).
B
B
H
130
(3)
6
7
2f
3f (61)
O
O
B
B
130
(23)
2g
3g (78)
O
O
B
B
NMe2
NMe2
110
8
(24)
2h
3h (99)
3i (73)
E
E
B
B
E
E
R1
2i
100
(16)
9c)
(Me2CO)2B
B
B
R1
R2
+
ð1Þ
(Me2CO)2B
R2
a) A solution of 1 (0.10 mmol) and 2 (0.11 mmol) in xylene
(2 mL) was stirred at the temperature for the hours indicated
above. B ¼ (pinacolato)boryl. b) Isolated yield. c) E ¼
CO2Me.
1
2
3
A solution of 1 and a slight excess of dienophile 2 in xylene
was heated under the conditions indicated in Table 1. Various
electron-deficient olefins were applicable to the cycloaddition.
Noteworthy is that dimerization of 1 was not observed at all
in view that some 2-boryl-1,3-dienes are reportedly to be high-
ly susceptible to dimerization.4c,4d Such cyclic alkenes as N-
phenylmaleimide (2a) and maleic anhydride (2b) gave bicyclic
products 3a and 3b quantitatively (Entries 1 and 2). cis- and
trans-Dimethyl 4,5-diborylcyclohex-4-ene-1,2-dicarboxylates
3c and 3d were obtained from dimethyl maleate (2c) and
fumarate (2d), respectively (Entries 3 and 4). Methyl acrylate
Published on the web April 10, 2008; doi:10.1246/bcsj.81.518

Bull. Chem. Soc. Jpn. Vol. 81, No. 4 (2008)
ꢀ 2008 The Chemical Society of Japan
519
0.10 mmol) and dienophile 2 (0.11 mmol) in xylene (2 mL) was
stirred at the temperature and for the time indicated in Table 1.
Removal of xylene under reduced pressure followed by gel perme-
ation chromatography gave 3.
2 Ph–I
Pd(PPh3)4 cat.
B
B
R1
R2
Ph
Ph
CO2Me
aq. K2CO3
THF, 80 °C
78% yield
3
2-Phenyl-5,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)-3a,4,7,7a-tetrahydroisoindole-1,3-dione (3a): Yield 99%; a
colorless solid; mp 152 ꢁC; Rf 0.10 (hexane/EtOAc 4:1). 1H NMR
(CDCl3) ꢀ 1.27 (s, 24H), 2.44–2.69 (m, 4H), 3.02–3.11 (m, 2H),
7.30–7.54 (m, 5H); 13C NMR (CDCl3) ꢀ 24.8, 27.4, 39.2, 83.8,
126.9, 128.4, 128.9, 132.1, 178.7; IR (neat) 2923, 2854, 1701,
1460, 1377, 1340, 1311, 1144, 1115, 1024 cmꢂ1; MS m=z 480
(Mþ þ 1, 5), 479 (Mþ, 17), 338 (100), 297 (51), 83 (47). Anal.
Calcd for C26H35B2NO6: C, 65.17; H, 7.36%. Found: C, 65.10;
H, 7.30%.
4
o-chloranil
benzene
80 °C, 92%
2 Ph–I
Pd(PPh3)4 cat.
B
B
CO2Me
CO2Me
Ph
Ph
CO2Me
CO2Me
K3PO4
DMF, 100 °C
94% yield
5
6
5,6-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3a,4,7,7a-
tetrahydroisobenzofuran-1,3-dione (3b): Yield 99%; colorless
oil; Rf 0.53 (hexane/EtOAc 1:1). 1H NMR (CDCl3) ꢀ 1.28 (s,
24H), 2.50–2.53 (m, 4H), 3.15–3.25 (m, 2H); 13C NMR (CDCl3) ꢀ
24.9, 26.6, 39.4, 84.1, 173.6; IR (neat) 1780, 1450, 1344, 1317,
1143, 1110, 1033, 928, 854 cmꢂ1; MS m=z 389 (Mþ ꢂ Me, 8.5),
346 (34), 263 (100), 149 (21), 83 (48). Anal. Calcd for C20H30-
B2O7: C, 59.45; H, 7.48%. Found: C, 59.33; H, 7.29%.
Dimethyl cis-4,5-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)cyclohex-4-ene-1,2-dicarboxylate (3c): Yield 94%; color-
less oil; Rf 0.21 (hexane/EtOAc 4:1). 1H NMR (CDCl3) ꢀ 1.28 (s,
24H), 2.44–2.93 (m, 4H), 2.94–3.00 (t, J ¼ 6:5 Hz, 2H), 3.66 (s,
6H); 13C NMR (CDCl3) ꢀ 24.9, 28.7, 39.1, 51.8, 83.6, 173.6; IR
(neat) 2927, 2931, 1731, 1437, 1342, 1305, 1146, 856, 756, 667
cmꢂ1; MS m=z 451 (Mþ þ 1, 3), 450 (Mþ, 9), 449 (Mþ ꢂ 1, 5),
350 (67), 83 (100). HRMS (FAB) Calcd for C22H36B2O8: Mþ
450.2596. Found: 450.2600.
Scheme 1.
(2e), acrolein (2f), methyl vinyl ketone (2g), and dimethyl
acrylamide (2h) also reacted with 1 to give 3e–3h in moderate
to good yields (Entries 5–8). Furthermore, cycloaddition with
dimethyl acetylenedicarboxylate (2i) gave rise to 1,2-diboryl-
ated 1,4-cyclohexadiene 3i in good yield (Entry 9). When the
cycloaddition reaction was monitored by TLC, tailing spots of
cycloadducts 3 were often observed. Attempted purification of
3 by preparative TLC resulted in failure due probably to insta-
bility of 3 toward silica gel. Hence, all products 3 were purified
by gel permeation chromatography.
Two examples of product transformation are shown in
Scheme 1. Pd-Catalyzed cross-coupling reaction of 3e with
two molar equivalents of iodobenzene in THF at 80 ꢁC gave
1,2,4-trisubstituted cyclohexene 4 in 78% yield. Meanwhile,
cyclohexadiene 3i was easily oxidized with o-chloranil at 80
ꢁC in benzene to give dimethyl 4,5-diborylphthalate 5 in 92%
yield, which also coupled with iodobenzene in the presence of
a palladium catalyst and a base, giving rise to o-terphenyl 6 in
excellent yield.
Dimethyl trans-4,5-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)cyclohex-4-ene-1,2-dicarboxylate (3d):
Yield 90%;
colorless oil; Rf 0.49 (hexane/EtOAc 1:1). 1H NMR (CDCl3) ꢀ
1.28 (s, 24H), 2.14–2.34 (m, 2H), 2.55–2.80 (m, 4H), 3.67 (s, 6H);
13C NMR (CDCl3) ꢀ 24.7, 31.5, 40.9, 51.7, 83.7, 175.5; IR (neat)
1735, 1624, 1458, 1438, 1377, 1344, 1307, 1145, 1114, 1028, 958,
856, 756 cmꢂ1; MS m=z 451 (Mþ þ 1, 3), 450 (Mþ, 9), 449
(Mþ ꢂ 1, 5), 350 (67), 83 (100). Anal. Calcd for C22H36B2O8: C,
58.70; H, 8.06%. Found: C, 58.40; H, 7.79%.
In summary, we have demonstrated that Diels–Alder reac-
tion of 2,3-bis(pinacolatoboryl)-2,3-butadiene constitutes a
facile synthetic method for 1,2-bis(pinacolatoboryl)cyclohex-
enes and the diboryl groups of the cycloadducts are easily
transformed into carbonaceous groups to give polysubstituted
cyclohexenes and benzenes conveniently.
Methyl 3,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
cyclohex-3-enecarboxylate (3e): Yield: 65%; colorless oil; Rf
0.21 (hexane/EtOAc 4:1). 1H NMR (CDCl3) ꢀ 1.28 (s, 24H),
1.95–3.66 (m, 7H), 3.66 (s, 3H); 13C NMR (CDCl3) ꢀ 24.8, 24.9,
28.3, 30.6, 39.1, 51.1, 83.5, 176.4; IR (neat) 2978, 2932, 2839,
1732, 1622, 1147, 1020, 856, 665 cmꢂ1; MS m=z 393 (Mþ þ 1, 3),
392 (Mþ, 12), 391 (Mþ ꢂ 1, 8), 292 (100), 83 (92). Anal. Calcd
for C20H34B2O6: C, 61.26; H, 8.74%. Found: C, 61.19; H, 8.44%.
3,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-cyclo-
hex-3-enecarbaldehyde (3f): Yield: 61%; colorless oil; Rf 0.35
(hexane/EtOAc 4:1). 1H NMR (CDCl3) ꢀ 1.29 (s, 24H), 1.97–2.02
(m, 1H), 2.19–2.47 (m, 6H), 9.67 (s, 1H); 13C NMR (CDCl3) ꢀ
21.9, 25.0, 27.5, 27.6, 46.0, 83.6, 204.5; IR (neat) 2978, 2925,
2856, 1726, 1620, 1306, 1146, 856, 665 cmꢂ1; MS m=z 364
(Mþ þ 2, 1), 363 (Mþ þ 1, 5), 362 (Mþ, 21), 262 (100), 221 (71),
83 (83). HRMS (FAB) Calcd for C19H32B2O5: Mþ 362.2436.
Found: m=z 362.2435.
Experimental
General. NMR spectra (1H and 13C) were measured on a
Varian Mercury 200 (200 MHz) spectrometer. Chemical shifts of
1H NMR are expressed in parts per million downfield relative
to internal tetramethylsilane (ꢀ 0) or chloroform (ꢀ 7.26). Split-
ting patterns are indicated as s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; brs, broad singlet. 13C NMR spectra were
recorded with tetramethylsilane as an internal standard (ꢀ 0). In-
frared spectra (IR) were recorded on a Shimadzu FTIR-8400 spec-
trometer. GC-MS analyses were obtained with a JEOL JMS-
700 spectrometer by electron ionization at 70 eV. Elemental anal-
yses were carried out with a YANAKO MT2 CHN CORDER
machine at Kyoto University Elemental Analysis Center. Melting
points were determined using a YANAKO MP-500D. Preparative
recycling gel permeation chromatography (GPC) was performed
with a JAI LC-908 chromatograph equipped with JAIGEL-1H
and -2H columns (chloroform as an eluent).
1-[3,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclo-
hex-3-enyl]ethan-1-one (3g): Yield: 78%; colorless oil; Rf 0.25
(hexane/EtOAc 4:1). 1H NMR (CDCl3) ꢀ 1.28 (s, 24H), 1.35–1.55
(m, 1H), 1.85–2.00 (m, 2H), 2.10–2.20 (s, 3H), 2.20–2.60 (m, 4H);
13C NMR (CDCl3) ꢀ 24.2, 24.9, 28.1, 28.6, 30.1, 47.1, 83.5, 211.8;
General Procedure for Diels–Alder Reaction of 2,3-Bis-
(pinacolatoboryl)-1,3-butadiene (1). A solution of 1 (31 mg,

520 M. Shimizu et al.
Bull. Chem. Soc. Jpn. Vol. 81, No. 4 (2008)
IR (neat) 2978, 2928, 1713, 1621, 1305, 1269, 1213, 1147, 1113,
856, 667 cmꢂ1; MS m=z 378 (Mþ þ 2, 1), 377 (Mþ þ 1, 4), 376
(Mþ, 19), 318 (15), 276 (100), 83 (79). Anal. Calcd for C20H34B2-
O5: C, 63.87; H, 9.11%. Found: C, 63.87; H, 8.93%.
N,N-Dimethyl 3,4-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)cyclohex-3-enecarboxyamide (3h): Yield: 99%; colorless
oil; Rf 0.48 (EtOAc). 1H NMR (CDCl3) ꢀ 1.27 (s, 24H), 2.24–2.96
(m, 6H), 2.97 (s, 6H); 13C NMR (CDCl3) ꢀ 24.9, 25.1, 28.7, 31.2,
36.4, 83.5, 175.9; IR (neat) 2978, 2929, 1643, 1456, 1342, 1304,
1146, 1014, 854, 663 cmꢂ1; MS m=z 406 (Mþ þ 1, 23), 405 (Mþ,
100), 350 (72), 205 (64), 83 (53). HRMS (FAB) Calcd for C21H37-
B2NO5: Mþ 405.2858. Found: m=z 405.2852.
1,2-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4,5-bis-
(methoxycarbonyl)cyclohexa-1,4-diene (3i): Yield 73%; color-
less solid; mp 137.9 ꢁC (hexane); Rf 0.20 (hexane/EtOAc 4:1).
1H NMR (400 MHz, CDCl3) ꢀ 1.29 (s, 24H), 3.08 (s, 4H), 3.75 (d,
J ¼ 0:4 Hz, 6H); 13C NMR (100 MHz, CDCl3) ꢀ 24.9, 30.3, 52.2,
83.8, 131.9, 168.2; IR (KBr) 2980, 2949, 2359, 2341, 1716, 1672,
1622, 1434, 1346, 1313, 1147, 1099, 1069, 1043, 962, 856, 796
cmꢂ1; MS m=z 448 (Mþ, 1), 275 (100). Anal. Calcd for C22H34-
B2O8: C, 58.96; H, 7.65%. Found: C, 58.76; H, 7.63%.
Cross-Coupling Reaction of 3e. A solution of 3e (28 mg,
0.072 mmol), iodobenzene (38 mg, 0.19 mmol), [Pd(PPh3)4] (6.7
mg, 5.7 mmol, 8 mol %), and 6 M aq K2CO3 (72 mL, 0.43 mmol)
in THF (2 mL) was stirred at 80 ꢁC for 16 h before quenching with
sat. aq NH4Cl (10 mL). The aqueous layer was extracted with
EtOAc (10 mL ꢃ 3) and then washed with sat. aq NaCl (10 mL).
The organic layer was dried over anhydrous MgSO4 and concen-
trated in vacuo. Purification of the residue by preparative TLC
(hexane/EtOAc 10:1) gave 4 (CAS NO. 62543-95-7, 17 mg, 78%
yield) as a colorless solid.
Oxidation of 3i. A solution of 3i (80 mg, 0.18 mmol) and o-
chloranil (101 mg, 0.41 mmol) in benzene (4 mL) was stirred at
80 ꢁC for 1 h. Removal of benzene under reduced pressure fol-
lowed by GPC gave 5 (74 mg, 92% yield) as a colorless solid.
Mp 153.9 ꢁC (hexane); Rf 0.20 (hexane/EtOAc 4:1). 1H NMR
(400 MHz, CDCl3) ꢀ 1.38 (s, 24H), 3.90 (s, 6H), 7.98 (d, J ¼
0:4 Hz, 2H); 13C NMR (100 MHz, CDCl3) ꢀ 25.0, 52.5, 84.4,
131.8, 133.3, 167.9; IR (KBr) 2980, 2951, 2359, 1726, 1499,
1435, 1371, 1330, 1292, 1148, 1092, 966, 856, 835, 804, 677,
665 cmꢂ1, MS m=z 446 (Mþ, 0.3), 305 (100). Anal. Calcd for
C22H32B2O8: C, 59.23; H, 7.23%. Found: C, 59.04; H, 7.16%.
Cross-Coupling Reaction of 5. A solution of 5 (20 mg, 0.045
mmol), iodobenzene (23 mg, 0.11 mmol), [Pd(PPh3)4] (4.2 mg,
3.6 mmol, 8 mol %), and K3PO4 (38 mg, 0.18 mmol) in DMF (2
mL) was stirred at 100 ꢁC for 6 h before quenching with sat. aq
NH4Cl (10 mL). Workup followed by purification with prepara-
tive TLC (hexane/EtOAc 10:1) gave 6 (CAS NO. 7111-79-7,
14 mg, 94% yield) as a colorless solid.
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This work was supported by Grant-in-Aid for Creative
Scientific Research, No. 16GS0209, from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.