LETTER
Asymmetric Mannich Reactions of Enol Ethers and Carbonyl Imines
473
(6) Giardina, A.; Mecozzi, T.; Petrini, M. J. Org. Chem. 2000,
65, 8277.
Method A).
Analytical data of compound (S,R,S)-4a:
24
(7) (a) Kise, N.; Ueda, N. J. Org. Chem. 1999, 64, 7511.
(b) Mooiweer, H. H.; Ettema, K. W. A.; Hiemstra, H.;
Speckamp, W. N. Tetrahedron 1990, 46, 2991. (c) Shono,
T.; Kise, N.; Sanda, F.; Ohi, S.; Yoshioka, K. Tetrahedron
Lett. 1989, 30, 1253. (d) Brown, D. S.; Earle, M. J.;
Fairhurst, R. A.; Heaney, H.; Papageorgiou, G.; Wilkins, R.
F.; Eyley, S. Synlett 1990, 619.
(8) (a) Ferraris, D.; Young, B.; Dudding, T.; Drury, W. J. III.;
Lectka, T. Tetrahedron 1999, 55, 8869; and literature cited
therein. (b) Juhl, K.; Gathergood, N.; Jørgensen, K. A.
Angew. Chem., Int. Ed. Engl. 2001, 40, 2995; Angew. Chem.
2001, 113, 3083.
(9) Enders, D.; Schunk, S. Org. Lett. 2001, 3, 3177.
(10) Enders, D.; Adam, J.; Klein, D.; Otten, T. Synlett 2000,
1371.
(11) (a) Enders, D.; Ward, D.; Adam, J.; Raabe, G. Angew.
Chem., Int. Ed. Engl. 1996, 35, 981; Angew. Chem. 1996,
108, 1059. (b) Enders, D.; Oberbörsch, S.; Adam, J. Synlett
2000, 644.
[ ]D
=
93.6 (CHCl3, c = 0.50). 1H NMR [400 MHz,
(CD3)2 CO]: = 0.08 (s, 3 H, SiCH3), 0.16 (s, 3 H, SiCH3),
0.90 (d, 3 H, J = 6.8, CHCH3), 0.91 (d, 3 H, J = 6.9,
CH3CHCH3), 0.93 (d, 3 H, J = 6.9, CH3CHCH3), 0.94 (s, 3
H, CH3CCH3), 0.95 (s, 3 H, CH3CCH3), 1.40 (s, 9 H,
OC(CH3)3), 1.77 (sept, 1 H, J = 6.9, CH3CHCH3), 2.77 (m,
1 H, CHHC6H4Br), 3.07 (qd, 1 H, J = 6.9, 3.3, CHCH3),
3.13–3.24 (m, 2 H, CHHC6H4Br, SiCH), 4.70 (d, 1 H, J =
8.3, CHNH), 6.00 (m, 1 H, NH), 6.66 (m, 2 H, CH-Ph), 7.10–
7.47 (m, 7 H, CH-C6H4Br, m/pCH-Ph) ppm. 13C NMR [100
MHz, (CD3)2CO]:
= 3.7 (SiCH3), 2.0 (SiCH3), 13.3
(CH3), 18.9 (CH3CHCH3), 19.1 (CH3CHCH3), 21.5
(CH3CCH3), 21.8 (CH3CCH3), 25.7 (CH3CCH3), 28.5
(OC(CH3)3), 33.7 (CH2C6H4Br), 34.9 (CH3CHCH3), 47.4
(SiCH), 53.1 (CHCH3), 56.5 (CHNH), 79.1 (OC(CH3)3),
120.0 (C-C6H4Br), 127.2 (pCH-Ph), 127.4 (CH-Ph), 128.4
(mCH-Ph), 131.2 (CH-C6H4Br), 132.0 (CH-C6H4Br), 140.4
(C-Ph), 142.1 (C-C6H4Br), 155.6 (OC=O), 211.8 (C=O)
ppm. MS (CI, isobutane): m/z (%): 591(35), 590 (100, M+ +
1), 589(33), 588(90), 534(47), 533(28), 532(48), 529(8),
526(6), 512(6), 511(22), 510(59), 504(7), 502(6), 491(14),
490(50), 489(14), 488(46), 454(15), 447(20), 446(12),
411(11), 410(36), 368(7), 305(7), 206(20), 150(9), 106(20).
Anal. Calcd. for C31H46NO3SiBr (588.70): C, 63.25; H, 7.88;
N, 2.38. Found: C, 63.22; H, 7.75; N, 2.30.
(12) Enders, D.; Otten, T. Synlett 1999, 747.
(13) (a) Engberts, J. B. F. N.; Strating, J. Recueil 1965, 84, 942.
(b) Engberts, J. B. F. N.; Strating, J. Recueil 1964, 83, 733.
(c) Pearson, W. H.; Lindbeck, A. C.; Kampf, J. W. J. Am.
Chem. Soc. 1993, 115, 2622. (d) Ballini, R.; Petrini, M.
Tetrahedron 1999, 40, 4449.
(14) Ireland, R. E.; Müller, R. H.; Willard, A. K. J. Am. Chem.
Soc. 1976, 98, 2868.
(15) Asymmetric Mannich Reactions:
(16) For removal of the dimethylthexylsilyl group see ref. 11b.
Analytical data of compound (R,S)-5a:
24
[ ]D
=
29.0 (CHCl3, c = 0.50). 1H NMR (400 MHz,
Method A: 1.2 Equiv potassium hydride was added to a
solution of 1.1 equiv carbamate 3 in dry CH2Cl2 (5 mL/mmol
3) under argon. After stirring for 1 h at r.t. the reaction
mixture was cooled to 78 °C. After addition of 1.1–1.5
equiv TiCl4 (1.0 N in CH2Cl2) and stirring for 20 min at this
temperature the solution was cooled to 90 °C. 1 equiv Silyl
enol ether 2 in dry CH2Cl2 (1 mL/mmol 2) was added
dropwise. The reaction mixture was stirred for 75 min at
CDCl3): = 1.14 (d, 3 H, J = 6.9, CHCH3), 1.41 (s, 9 H,
OC(CH3)3), 2.15–2.70 (m, 4 H, CH2CH2), 3.05 (m, 1 H,
CHCH3), 4.81 (m, 1 H, CHNH), 5.87 (m, 1 H, NH), 6.87 (d,
2 H, J = 8.3, CH-Ph), 7.10–7.35 (m, 7 H, CH-C6H4Br, m/
pCH-Ph) ppm. 13C NMR (100 MHz, CDCl3): = 15.1 (CH3),
28.3 (OC(CH3)3), 28.4 (CH2C6H4Br), 44.2 (CH2CO), 51.0
(COCHCH3), 57.0 (CHNH), 79.4 (OC(CH3)3), 119.6 (C-
C6H4Br), 125.9 (pCH-Ph), 127.1 (CH-Ph), 128.4 (mCH-Ph),
129.8 (CH-C6H4Br), 131.2 (CH-C6H4Br), 139.6 (C-Ph),
141.0 (C-C6H4Br), 155.3 (OC=O), 213.2 (C=O) ppm. MS
(EI, 70 eV): m/z (%): 447 (1, M+), 390(23), 389(21), 211(4),
207(4), 206(34), 184(4), 182(4), 170(13), 169(13), 151(9),
150(100), 147(4), 134(4), 132(7), 118(15), 117(9), 107(6),
106(70), 104(9), 77(5), 57(59). Anal. Calcd. for
90 °C
78 °C, then quenched with a saturated solution
of NaHCO3, extracted with CH2Cl2 and dried over MgSO4.
After evaporation of the solvent, the crude Mannich adducts
4 were purified by flash chromatography (SiO2, n-pentane/
Et2O).
Method B: A solution of 1.1 equiv carbamate 3 in dry
CH2Cl2 (5 mL/mmol) under argon was cooled to 78 °C.
After addition of 1.1–1.5 TiCl4 (1.0 N in CH2Cl2) and
stirring for 20 min at this temperature the solution was
cooled to 90 °C. 1 equiv Silyl enol ether 2 in dry CH2Cl2 (1
mL/mmol 2) was added dropwise. (Further procedure see
C23H28NO3Br (446.38): C 61.89, H 6.23, N 3.14. Found: C,
61.82; H, 6.30; N, 3.00.
(17) All new compounds showed suitable spectroscopic data
(NMR, MS, IR) and correct elemental analyses.
Synlett 2002, No. 3, 471–473 ISSN 0936-5214 © Thieme Stuttgart · New York