LETTER
Cu-Catalyzed Asymmetric Hydroboration of Aldimines
441
(11) For an important synthetic use of enantioenriched α-
Table 2 Chiral (N-Alkyl, N-Aryl)-Hybrid NHC6/CuCl-Catalyzed
Asymmetric Hydroboration of Different Aldiminesa
(acylamino)benzylboronic esters in Suzuki–Miyaura
coupling, see: (a) Ohmura, T.; Awano, T.; Suginome, M. J.
Am. Chem. Soc. 2010, 132, 13191. (b) Awano, T.; Ohmura,
T.; Suginome, M. J. Am. Chem. Soc. 2011, 133, 20738.
(12) O’Brien, J. M.; Lee, K.-S.; Hoveyda, A. H. J. Am. Chem.
Soc. 2010, 132, 10630.
(13) (a) Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131,
3160. (b) Corberán, R.; Mszar, N. W.; Hoveyda, A. H.
Angew. Chem. Int. Ed. 2011, 50, 7079.
Ph
Ph
CuCl (10 mol%)
NHC6 (12 mol%)
HN
O
O
O
O
O
B
B
N
O
+
O
R
t-BuONa (24 mol%)
toluene, 12 h, r.t.
B
R
H
O
3
1
2
(1.2 equiv)
(14) Lee, Y.; Jang, H.; Hoveyda, A. H. J. Am. Chem. Soc. 2009,
131, 18234.
(15) For a recent review about synthetic routes to N-heterocyclic
carbene precursors, see: Benhamou, L.; Chardon, E.;
Lavigne, G.; Bellemin-Laponnaz, S.; César, V. Chem. Rev.
2011, 111, 2705.
9 examples
29–94% yield
41–84% ee
1a R = Ph
1b R = 4-F-C6H4
1c R = 4-Br-C6H4
1d R = 4-MeO-C6H41e R = 3-MeO-C6H41f R = 2-MeO-C6H4
1g R = 2-F-C6H4 1h R = Cy
1i R = c-Bu
Entry Product
Entry Product
(16) See Supporting Information for the detailed procedure of the
preparation of chiral imidazolinium salts NHC2–NHC7.
Analytical data of some typical imidazolinium salts: NHC5:
[α]D23 +318.7 (c = 1.37, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 9.86 (s, 1 H), 8.17 (d, J = 7.6 Hz, 1 H), 7.17–
7.56 (m, 16 H), 6.97 (d, J = 7.6 Hz, 2 H), 4.99 (d, J = 10.0
Hz, 1 H), 4.39 (d, J = 10.0 Hz, 1 H), 3.88 (s, 3 H). 13C NMR
(100 MHz, CDCl3): δ = 158.04, 137.94, 137.77, 134.10,
133.95, 132.02, 130.82, 129.83, 129.64, 129.51, 129.42,
129.16, 129.10, 129.04, 128.58, 128.28, 127.48, 75.83,
74.60, 35.20. MS (ESI): m/z = 389.2 [C28H25IN2 – I]+.
HRMS: m/z [M]+ calcd for C28H25N2: 389.20177; found:
389.20140. NHC6: [α]D23 +454.0 (c = 0.845, CHCl3). 1H
NMR (400 MHz, CDCl3): δ = 8.67 (s, 1 H), 7.54 (m, 3 H),
7.32–7.42 (m, 10 H), 7.12–7.17 (m, 3 H), 6.81 (d, J = 7.6 Hz,
2 H), 5.14 (d, J = 8.8 Hz, 1 H), 3.88 (m, 1 H), 1.69–1.94 (m,
6 H), 1.54 (m, 1 H), 1.32–1.42 (m, 1 H), 1.09–1.27 (m, 3 H),
1.19 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ = 155.83,
152.92, 138.12, 135.44, 135.39, 134.82, 131.53, 130.44,
129.94, 129.58, 129.44, 129.22, 129.18, 128.21, 127.92,
127.23, 126.46, 75.96, 72.09, 57.94, 34.65, 31.44, 30.75,
25.08, 24.90, 24.44. MS (ESI): m/z = 513.3 [M – BF4]+.
Ph
Ph
O
HN
O
HN
O
O
B
1
2
B
O
O
F
3a, 82%b (63% ee)c
3b, 92%b (74% ee)c
Ph
Ph
HN
O
HN
O
O
O
B
B
3
5
7
9
4
6
8
O
O
Br
MeO
3c, 86%b (74% ee)c
3d, 90%b (69% ee)c
Ph
Ph
MeO HN
O
HN
O
MeO
O
O
B
B
+
HRMS: m/z [M – BF4]+ calcd for C37H41N2 : 513.32697;
O
O
found: 513.32435.
(17) Park, J. K.; Lackey, H. H.; Rexford, M. D.; Kovnir, K.;
Shatruk, M.; McQuade, D. T. Org. Lett. 2010, 12, 5008.
(18) For pharmaceutically interesting α-amido boronic acids, see:
(a) Contreras-Martel, C.; Amoroso, A.; Woon, E. C. Y.;
Zervosen, A.; Inglis, S.; Martins, A.; Verlaine, O.; Rydzik,
A. M.; Job, V.; Luxen, A.; Joris, B.; Schofield, C. J.; Dessen,
A. ACS Chem. Biol. 2011, 6, 943. (b) Woon, E. C. Y.;
Zervosen, A.; Sauvage, E.; Simmons, K. J.; Zivec, M.;
Inglis, S. R.; Fishwick, C. W. G.; Gobec, S.; Charlier, P.;
Luxen, A.; Schofield, C. J. ACS Med. Chem. Lett. 2011, 2,
219. (c) Morandi, F.; Caselli, E.; Morandi, S.; Focia, P. J.;
Blazquez, J.; Shoichet, B. K.; Prati, F. J. Am. Chem. Soc.
2003, 125, 685.
(19) General Procedure for NHC6/CuCl-Catalyzed
Asymmetric Hydroboration of Aldimines: In the
glovebox, an oven-dried Schlenk tube equipped with a stir
bar, imidazolinium tetrafluoroborate salt NHC6 (36 mg, 0.06
mmol), t-BuONa (12 mg, 0.12 mmol), and CuCl (5 mg, 0.05
mmol) were placed and anhyd toluene (2.0 mL) was added.
After the solution was allowed to stir for 2 h at 25 °C under
an anhyd N2 atmosphere, it was filtered through a syringe
filter (rinsed with 1.0 mL of toluene) and placed in a separate
oven-dried Schlenk tube. The resulting solution was charged
with B2(Pin)2 (2, 152 mg, 0.6 mmol) and N-benzoyl aldimine
(0.5 mmol). The Schlenk tube was removed from the
glovebox and the mixture was allowed to stir for 12 h at r.t.
After the reaction completed, the mixture was filtered
3e, 91%b (41% ee)c
3f, 90%b (64% ee)c
Ph
Ph
F
HN
O
HN
O
O
O
B
B
O
O
3g, 94%b (71% ee)c
3h, 40%b (80% ee)c
Ph
HN
O
O
B
O
3i, 29%b (84% ee)c
a The reaction was carried out with 1 (0.5 mmol), B2Pin2 (2, 0.6 mmol,
120 mol%), CuCl (0.05 mmol, 10 mol%), NHC (12 mol%) and t-BuONa
(0.12 mmol, 24 mol%) in toluene (3 mL) for 12 h at r.t.
b Yield of the isolated product.
c Determined by chiral HPLC analysis.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 437–442