Cationic Palladium Complex-Catalyzed Diastereoselective Tandem Annulation of 2-Iminoarylboronic Acids
General Procedure for the Synthesis of 2-Imino-
arylboronic acids (1a–1h)
Representative Example for Chiral Cationic
Palladium-Catalyzed Diastereoselective Tandem
Annulation Reaction of Chiral 2-Iminoarylboronic
Acids and Alkynes
The 2-formylboronic acids (6.6 mmol) and the substituted
aniline (6.6 mmol) were dissolved in EtOH (35 mL) and tol-
uene (5 mL). The reaction mixture was heated to reflux
overnight till the reaction was completed. Then the reaction
mixture was cooled to room temperature and the solvent
was removed under reduced pressure and the residue was
purified by recrystallization to give the desired product 1.
To a Schlenk tube were added (S)-2-(N-tert-butanesulfinyl-
AHCTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
2-butynoate 2a (19.6 mg, 0.2 mmol, 2 equiv.) and dioxane
(2.0 mL) successively. The reaction mixture was stirred at
room temperature for 20 minutes until 5a had disappeared
as monitored by TLC. Then, the mixture was purified by
flash column chromatography (pure petroleum ether, then
ethyl acetate: petroleum ether=1:1) to obtain the product
1
Product 1a: yield: 80%; yellow solid; mp 220-222 8C; H
NMR (300 MHz, CDCl3): d=8.71 (s, 1H), 7.72 (d, J=
6.6 Hz, 2H), 7.34–7.25 (m, 5H), 7.16 (d, J=6.3 Hz, 1H),
6.80 (d, J=8.4 Hz, 2H), 3.75 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=163.5, 158.9, 139.3, 138.6, 131.9, 131.5, 128.1,
126.3, 123.3, 114.4, 55.4; IR (KBr): n=2835, 1616, 1506,
1341, 1249, 838 cmÀ1; MS (70 eV, EI): m/z (%)=255 (M+),
238, 211, 196 (100), 108, 80; HR-MS: m/z=255.1066, calcd.
for C14H14BNO3 (M+): 255.1067.
1
6aa as an oil; H NMR (400 MHz, CDCl3): d=7.68–7.66 (m,
1H), 7.45-7.27 (m, 3H), 5.11 (dd, J=1.5 and 4.5 Hz, 1H),
3.95 (d, J=4.5 Hz, 1H), 3.85 (s, 3H), 2.50 (d, J=1.2 Hz,
3H), 1.19 (s, 9H); 13C NMR (100 MHz, CDCl3): d=165.6,
152.0, 143.8, 143.2, 132.5, 128.8, 128.6, 124.9, 121.3, 63.0,
55.8, 51.3, 22.5, 12.5; IR (neat): v=3205, 2952, 2869, 1708,
1618, 1584, 1245, 1061 cmÀ1; MS (70 eV, EI): m/z (%)=307
(M+), 251, 219, 188, 155 (100), 128, 111, 57; HR-MS: m/z=
307.1240, calcd. for C16H21NO3S (M+): 307.1242; [a]D20: +68.4
(c 1.1000, CHCl3).
General Procedure for Cationic Palladium-Catalyzed
Tandem Reactions of 2-Iminoarylboronic Acids and
Alkynes
To a Schlenk tube were added 2-iminophenylboronic acidÀ1a
(25.5 mg, 0.1 mmol, 1 equiv.), [PdACTHUGNTRNE(NNUG dppp)ACHTNURGTENNUNG ACTHNUGTERNN(UNG BF4 )2
(H2O)2]2+
(2.2 mg, 3 mol%) and 2-butynoate 2a (19.6 mg, 0.2 mmol,
2 equiv.) and dioxane (2.0 mL) successively. The reaction
mixture was stirred at 808C for several hours until 2-imino-
phenylboronic acid had disappeared as monitored by TLC.
Then, the mixture was purified by flash column chromatog-
raphy (pure petroleum ether, then ethyl acetate: petroleum
ether=1:7) to obtain the product 3aa as an oil. 1H NMR
(300 MHz, CDCl3): d=7.53–7.34 (m, 4H), 6.64 (d, J=
8.1 Hz, 2H), 6.41 (d, J=8.1 Hz, 2H), 5.15 (s, 1H), 3.77 (s,
3H), 3.68 (s, 3H), 2.49 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=165.7, 152.7, 152.3, 145.9, 142.4, 141.1, 131.9, 128.7, 128.1,
123.6, 121.4, 116.5, 114.4, 63.1, 55.5, 51.2, 12.5; IR (neat): n=
3387, 2951, 2835, 1704, 1512, 1242, 1037, 763 cmÀ1; MS (70
eV, EI): m/z (%)=309 (M+), 277, 250, 155, 122 (100); HR-
MS: m/z=309.1360, calcd. for C19H19NO3 (M+): 309.1365.
Transformation of 6aa and 6aa’ to Their Acetyl
Derivatives 7aa and 7aa’
To a solution of the N-sulfinyl product (6aa or 6aa’) in 2 mL
of dry ethanol was added a solution of dry HCl in 1,4-diox-
ane (7.5 M, 5.0 equiv. based on 6aa or 6aa’). The mixture
was stirred at room temperature for 3 h and concentrated.
The resulting amine hydrochloride was precipitated with di-
ethyl ether. The amine hydrochloride (1.0 equiv.) was dis-
solved in CH2Cl2 (0.1 M) and Hꢂnigꢀs base (6.0 equiv.) was
added dropwise. Then, Ac2O (3.0 equiv.) was added and the
resulting mixture was stirred for 1 h at room temperature.
The reaction mixture was quenched with a saturated solu-
tion of ammonium chloride and diluted with CH2Cl2. The
resulting mixture was separated, and the aqueous layer was
extracted with CH2Cl2 three times. The combined organic
layer was dried over Na2SO4 and concentrated under re-
duced pressure. The residue was subjected to silica gel chro-
matography (eluent: EtOAc/petroleum ether) to offer the
General Procedure for the Synthesis of 2-(N-tert-
Butanesulfinyl)iminoarylboronic Acids (5a–5d)
1
The 2-formylboronic acids (6.6 mmol) and the N-tert-but-
product 7aa as a white solid; mp 132–1338C; H NMR (400
A
MHz, CDCl3): d=7.52-7.50 (m, 1H), 7.42-7.35 (m, 3H),
6.00-5.97 (m, 1H), 5.68 (d, J=8.4 Hz, 1H), 3.79 (s, 3H), 2.49
(d, J=2.4 Hz, 3H), 2.05 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=170.3, 165.2, 154.6, 145.2, 142.5, 129.8, 129.2,
128.3, 124.1, 121.3, 55.9, 51.3, 23.3, 12.5; IR (KBr): n=3270,
3072, 1708, 1643, 1549, 1240, 1199, 1065, 759 cmÀ1; MS (70
eV, EI): m/z (%)=245 (M+), 227, 213, 202, 170 (100), 143,
115, 43; HR-MS: m/z=245.1061, calcd. for C14H15NO3 (M+):
245.1052.
(35 mL) and toluene (5 mL). The reaction mixture was
heated to reflux overnight till the reaction was completed.
Then the reaction mixture was cooled to room temperature,
the solvent was removed under the reduced pressure and
the residue was purified by recrystallization to give the de-
sired product 5.
Product 5a: yield: 82%; white solid; mp 146–148 8C;
1H NMR (300 MHz, CDCl3): d=9.18 (s, 1H), 8.14–8.11 (m,
1H), 7.96–7.94 (m, 1H), 7.57–7.54 (m, 2H), 7.25 (s, 2H),
1.30 (s, 9H); 13C NMR (100 MHz, CDCl3): d=166.9, 136.6,
131.8, 130.7, 130.5, 58.1, 22.4; IR (KBr): n=3550, 2983,
2963, 2866, 1606, 1581, 1558, 1344, 1039, 765 cmÀ1; MS
(ESI): m/z (%)=276 (M+ +Na), 268, 255, 254 (100), 236;
anal. calcd. for C11H16BNO3S: C 52.19, H 6.37, N 5.53;
found: C 52.37, H 6.44, N 5.20; [a]2D0: +88.9 (c 1.0800,
CHCl3).
1
Product 7aa’: white solid, mp 1338C; H NMR (400 MHz,
CDCl3): d=7.53-7.50 (m, 1H), 7.42–7.35 (m, 3H), 6.00 (d,
J=10.4 Hz, 1H), 5.67 (d, J=10.4 Hz, 1H), 3.79 (s, 3H), 2.49
(d, J=1.6 Hz, 3H), 2.06 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=170.3, 165.2, 154.6, 145.2, 142.5, 129.8, 129.2,
128.3, 124.1, 121.3, 55.9, 51.3, 23.3, 12.5; IR (KBr) n=3273,
3070, 1712, 1640, 1544, 1243, 1196, 1061, 754 cmÀ1; MS (70
eV, EI): m/z (%)=245 (M+), 227, 213, 202, 170 (100), 143,
Adv. Synth. Catal. 2011, 353, 2805 – 2813
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2811