Table 1 Enantioselective silane terminated Heck reactions of the allyl silanes 1–4 and 7–10 to give the benzazepines 5 and 6 and the tetrahydroisoquinolines
11 and 12
Pd
Yield (%)
Eea (%)
Substrate
(Config.)
Catalyst
(mol%)
Ligand
(mol%)
Entry
R
Product
t/h
T/°C
a
b
a
b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1 (Z)
1 (Z)
1 (Z)
1 (Z)
1 (Z)
2 (Z)
2 (Z)
2 (Z)
2 (Z)
3 (E)
3 (E)
4 (E)
4 (E)
7 (E)
7 (E)
7 (E)
8 (E)
8 (E)
9 (Z)
9 (Z)
10 (Z)
10 (Z)
OMe
OMe
OMe
OMe
OMe
H
H
H
H
OMe
OMe
H
H
H
H
H
OMe
OMe
H
5
5
5
5
5
6
6
6
6
5
5
6
5b
3
3
3
1.5
3
3
3
3
1.5
3
1.5
1.5
3
3
3
3
3
1.5
1.5
3
PPh3 (10)c
15 (7)
14 (7)
ent-16 (7)
13 (15)
16 (15)
15 (15)
14 (15)
13 (15)
14 (10)
13 (7)
14 (15)
13 (15)
16 (7)
14 (7)
13 (7)
6
80
80
80
80
80
90
90
90
90
80
80
80
80
80
70
80
80
80
80
90
80
80
4
15
2
7
—
4
6
—
6
66
57
42
25
40
14
38
42
9
70
42
42
72
71
73
49
72
71
21
33
41
43
32
51
35
24
56
80
61
80
73
—
—
65
19
40
68
27
168
24
27
24
45
26
16
20
14
46
48
48
65
63
20
64
< 5 (S)
< 25 (R)
< 20 (R)
64 (S)
92 (S)
48 (R)
28 (R)
42 (R)
70 (S)
≈ 60 (S)
≈ 45 (S)
22 (S)
64 (R)
67 (R)
50 (R)
< 5 (S)
34 (R)
56 (R)
84 (S)
86 (S)
16 (S)
84 (S)
d
—
< 18 (R)
—
d
—
d
—
—
—
d
91 (S)
8 (R)
86 (S)
12 (R)
2 (R)
0
< 5 (R)
30 (R)
76 (R)
—
6
11
11
11
12
12
11
11
12
12
14 (7)
13 (10)
13 (10)
13 (15)
14 (7)
—
—
6
H
OMe
OMe
—
< 10 (R)
—
1
13 (20)
—
a Determined by chiral HPLC (Baker CHIRALCEL OD-R). b Pd(OAc)2 was used instead of Pd2dba3·CHCl3. c KOAc (4 eq.) and NPr4Br (1 eq.) were used
instead of Ag3PO4. d Not determined.
12b were obtained with high enantioselectivities of 86 and 84%
ee, and complete regioselectivity (entries 20 and 22).
These results together with the investigations of inter-
molecular Heck reactions3a clearly show that the novel ligands
13 and 14 are superior to known ligands, at least in the
investigated transformations.
This work has been supported by the Fonds der Chemischen
Industrie. We thank the Degussa AG for a generous gift of
precious metals and the Hoffmann-La Roche AG for ligand 15.
We are also greatly indebted to Dr S. Console (Chemi SpA) for
providing the new ligands.
Notes and references
1 Reviews: M. Beller, T. H. Riermeier and G. Stark, in Transition Metals
for Organic Synthesis, ed. M. Beller and C. Bolm, Wiley–VCH,
Weinham, 1998, p. 208; S. Bräse and A. de Meijere, in Metal-Catalyzed
Cross Coupling Reactions, eds. P. J. Stang and F. Diederich, Wiley–
VCH, Weinham, 1997, p. 99.
2 Reviews: J. T. Link and L. E. Overman, in Metal-Catalyzed Cross
Coupling Reactions, ed. P. J. Stang and F. Diederich, Wiley–VCH,
Weinheim, 1997, p. 231; L. F. Tietze, T. Nöbel and M. Spescha, J. Am.
Scheme 3 Syntheses of the (E)- and (Z)-allyl silane precursors. Reagents
Chem. Soc., 1998, 120, 8971; L. F. Tietze and H. Schirok, J. Am. Chem.
and conditions: a, H2, Ni(OAc)2, NaBH4, ethylenediamine, EtOH; 1: 65%,
Soc., 1999, 121, 10264; J. Jin and S. M. Weinreb, J. Am. Chem. Soc.,
2: 90%, 9: 88%, 10: 60%; b, LiAlH4, THF, heat; 50%; c, 1. Pri2NEt, MeCN–
1997, 119, 5773; M. Brenner, G. Mayer, A. Terpin and W. Steglich,
MeOH, 50 °C; 2. (CF3CO)2O, NEt3, THF, 0 °C ? r.t.; 3: 42%, 4: 40%; d,
Chem. Eur. J., 1997, 3, 70.
1. (CF3CO)2O, NEt3, THF, 0 °C ? r.t.; 2. NaH, DMF, 0 °C ? r.t.; 7: 75%;
3 (a) L. F. Tietze, K. Thede and F. Sannicolò, Chem. Commun., 1999, 1811;
e, 1. (CF3CO)2O, NEt3, THF, 0 °C ? r.t.; 2. MsCl, NEt3, CH2Cl2, 0 °C ?
(b) F. Miyazaki, K. Uotsu and M. Shibasaki, Tetrahedron, 1998, 54,
r.t.; NaH, DMF, 0 °C ? r.t.; 8: 39%.
13073; (c) S. Y. Cho and M. Shibasaki, Tetrahedron Lett., 1998, 39,
1773; (d) review: M. Shibasaki, C. D. J. Boden and A. Kojima,
Tetrahedron, 1997, 53, 7371; (e) O. Loiseleur, M. Hayashi, N. Schmees
trimethylsilylvinyl side chain is the main product, with 14 as the
best ligand; thus, 13 gave 5a with only 8% ee (entry 11).
Interestingly, in the Heck reaction of the (Z)- and the (E)-allyl
silanes with 14 and 13 the opposite enantiomers of 6b were
formed, whereas in the presence of 16 the double bond
configuration had virtually no influence on the facial selectiv-
ity.
Astoundingly, the Heck reactions of the (E)-allyl silanes 7
and 8 were only marginally successful. Here the regio- and
enantio-selectivity were rather low. However, the (Z)-com-
pounds 9 and 10 gave much better results. Using 13 as chiral
ligand, the vinyl substituted tetrahydroisoquinolines 11b and
and A. Pfaltz, Synthesis, 1997, 1338; (f) T. Ohshima, K. Kagechika, M.
Adachi, M. Sodeoka and M. Shibasaki, J. Am. Chem. Soc., 1996, 118,
7108; (g) L. F. Tietze and T. Raschke, Liebigs Ann. Chem., 1996, 1981;
(h) L. F. Tietze and T. Raschke, Synlett, 1995, 597; (i) L. F. Tietze and R.
Schimpf, Angew. Chem., Int., Ed. Engl., 1994, 33, 1089.
4 (a) P. Antognazza, T. Benincori, E. Brenna, E. Cesarotti, L. Trimarco and
F. Sannicolò EP 0770085 to Chemi SpA; (b) T. Benincori, E. Brenna, F.
Sannicolò, L. Trimarco, P. Antognazza, E. Cesarotti, F. Demartin and T.
Pilati, J. Org. Chem., 1996, 61, 6244.
5 R. Schmid, J. Foricher, M. Cereghetti and P. Schönholzer, Helv. Chim.
Acta, 1991, 74, 370.
Communication a909689b
584
Chem. Commun., 2000, 583–584