Communications
Table 2: Rhodium-catalyzed parallel kinetic resolution of 3-substituted 4-alkynals to yield enantioen-
riched 2-alkylideneglutarimides and cyclopentenones.[a]
Experimental Section
Representative procedure (Table 2, entry 5): In
an Ar atmosphere, a solution of (S)-segphos
(12.2 mg, 0.020 mmol) in CH2Cl2 (1.0 mL) was
added to a solution of [Rh(cod)2]BF4 (8.1 mg,
G
0.020 mmol) in CH2Cl2 (1.0 mL), and the result-
ing mixture was stirred for 5 min. H2 was intro-
duced to the reaction solution in a Schlenktube.
The resulting solution was concentrated to dry-
ness after stirring for 0.5 h at room temperature.
3-Methylnon-4-ynal (1a; 60.9 mg, 0.400 mmol)
and n-butyl isocyanate (2a; 19.8 mg, 0.20 mmol)
were added to the residue by using CH2Cl2
(2.0 mL), and the reaction mixture was stirred at
room temperature for 20 h. The resulting solution
was concentrated and purified by chromatogra-
phy on silica gel (hexane/EtOAc 12:1), which
furnished (R)-(+)-1-butyl-4-methyl-3-pentylide-
nepiperidine-2,6-dione ((S)-(+)-3aa; 38.5 mg,
Entry
1
R1
R2
2
R3
3
4
Yield [%][b]
ee [%][c]
Yield [%][b]
ee [%][c]
1
2
3
4
1h
1h
1h
1h
1a
1i
1c
1e
1 f
nBu
nBu
nBu
nBu
nBu
nBu
Cy
nBu
nBu
nBu
nBu
Me
Ph
2a
2b
2c
2d
2a
2a
2a
2a
2a
nBu
Cy
Bn
Ph20
nBu
nBu
nBu
nBu
nBu
34
30
36
91
81
88
28
38
26
92
94
91
52
38
94
5
38
22
33
49
35
87
97
64
56
72
39
36
30
26
31
83
78
98
85
76
6[d]
7[d]
8
0.153 mmol, 38% yield, 87% ee) as
a pale-
Me
Me
yellow oil and (S)-(+)-2-butyl-4-methylcyclo-
pent-2-enone ((R)-(+)-4a; 23.9 mg, 0.157 mmol,
39% yield, 83% ee) as a colorless oil. (S)-(+)-
3aa: [a]2D5 + 56.38 (CHCl3, c = 1.625, 87% ee); IR
(neat) 2920, 2855, 1710, 1662, 1635, 1430, 1330,
1-cyclohexenyl
PhMe
9[d]
[a] Reactions were carried out with 1 (0.40 mmol), 2 (0.20 mmol), [Rh(cod)2]BF4 (0.020 mmol), (S)-
segphos (0.020 mmol), and CH2Cl2 (2.0 mL). [b] Yields of the isolated products. [c] The ee values were
determined by chiral HPLC or GC analysis. [d] Catalyst=10 mol%.
A
1176, 1122, 728 cmÀ1
;
1H NMR (CDCl3,
300 MHz) d = 6.92 (t, J = 7.8 Hz, 1H), 3.70–3.93
(m, 2H), 3.06–3.20 (m, 1H), 2.71 (dd, J = 16.2 and
5.4 Hz, 1H), 2.62 (dd, J = 16.2 and 2.4 Hz, 1H),
2.10–2.33 (m, 2H), 1.24–1.59 (m, 8H), 1.10 (d, J =
7.2 Hz, 3H), 0.93 ppm (t, J = 7.8 Hz, 6H);
13C NMR (CDCl3, 75 MHz) d = 171.5, 165.9,
142.7, 131.8, 39.8, 39.3, 30.8, 30.1, 27.7, 26.2,
22.5, 20.3, 20.0, 13.82, 13.76 ppm; HRMS (EI)
calcd for C15H25NO2: [M]+ 251.1885, found
251.1847; chiralpakAS, hexane/ iPrOH (98:2),
1.0 mLminÀ1, retention times: 4.9 min (minor
isomer) and 5.6 min (major isomer). (R)-(+)-4a:
[a]2D5 + 84.68 (CHCl3, c = 0.950, 83% ee);
1H NMR (CDCl3, 300 MHz) d = 7.13–7.21 (m,
Scheme 4. Intermolecular [4+2] annulation of 5-trimethylsilyl-4-alkynal 1j withisocyanate 2a.
1H), 2.81–2.94 (m, 1H), 2.63 (dd, J = 18.9 and 6.3 Hz, 1H), 2.08–2.19
(m, 2H), 1.96 (dd, J = 18.9 and 2.1 Hz, 1H), 1.26–1.52 (m, 4H), 1.17
(d, J = 6.9 Hz, 3H), 0.91 ppm (t, J = 6.6 Hz, 3H); 13C NMR (CDCl3,
75 MHz) d = 209.8, 162.5, 145.4, 43.3, 33.3, 29.8, 24.2, 22.4, 20.4,
13.8 ppm; chiraldex G-TA column, 908C isothermal, retention times:
19.5 min (major isomer) and 21.4 min (minor isomer).[20]
Received: December 16, 2005
Published online: March 20, 2006
Keywords: aldehydes · alkynes · annulation ·
.
asymmetric catalysis · parallel kinetic resolution
[1] For reviews of transition-metal-catalyzed cycloadditions, see:
a) I. Ojima, M. Tzamarioudaki, Z. Li, R. J. Donovan, Chem.Rev.
1996, 96, 635 – 662; b) M. Lautens, W. Klute, W. Tam, Chem.Rev.
1996, 96, 49 – 92; c) J. E. Robinson in Modern Rhodium-Cata-
lyzed Organic Reactions (Ed.: P. A. Evans), Wiley-VCH, 2005,
p. 241.
[2] For review, see: J. A. Varela, C. Saà, Chem.Rev. 2003, 103, 3787 –
3801.
[3] a) P. Hong, H. Yamazaki, Tetrahedron Lett. 1977, 18, 1333 – 1336;
b) R. A. Earl, K. P. C. Vollhartd, J.Org.Chem. 1984, 49, 4786 –
4800; c) L. V. R. Bonaga, H.-C. Zhang, A. F. Moretto, H. Ye,
Scheme 5. Plausible reaction mechanism for the rhodium-catalyzed
intermolecular [4+2] annulation of 4-alkynals withisocyanates.
2736
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 2734 –2737