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DOI: 10.1055/s-0029-1217552
CaSH Organocatalysis: Enantioselective Friedel-Crafts Alkylation of Indoles with α,β-Unsaturated Aldehydes
Publikationsverlauf
Publikationsdatum:
10. Juli 2009 (online)

Abstract
Enantioselective Friedel-Crafts alkylation of indole with α,β-unsaturated aldehyde was catalyzed by camphor sulfonyl hydrazine (CaSH) with good enantioselectivity (81-88%).
Key words
camphor sulfonyl hydrazine (CaSH) - organocatalysis - indole alkylation - α,β-unsaturated aldehydes
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- Supporting Information (PDF)
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References and Notes
Aldehyde 3
(R¹ = Me): ¹H
NMR (400 MHz, CDCl3): δ = 9.75 (s,
1 H), 7.63 (d, J = 8.0
Hz, 1 H), 7.31 (m, 1 H), 7.26 (m, 1 H), 7.14 (m, 1 H), 6.84 (s,
1 H), 3.75 (s, 3 H), 3.68 (m, 1 H), 2.87 (m, 1 H), 2.71 (m, 1 H),
1.43 (d, J = 6.8
Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 203.1,
137.4, 126.8, 125.4, 121.9, 119.3, 119.0, 109.6, 51.2, 32.9, 26.1,
21.9 ppm.
Alcohol 4 was obtained
by NaBH4 reduction. Alcohol 4 (R¹ = Me): ¹H
NMR (400 MHz, CDCl3): δ = 7.64 (dd, J = 8.0, 0.8
Hz, 1 H), 7.30 (dd, J = 7.2,
0.8 Hz, 1 H), 7.23 (m, 1 H), 7.10 (m, 1 H), 6.85 (s, 1 H), 3.75
(s, 3 H), 3.66 (m, 1 H), 3.22 (m, 1 H), 2.06 (m, 1 H), 1.96 (m,
1 H), 1.40 (d, J = 6.8
Hz, 3 H) ppm.
General Experimental
Procedure for CaSH 1 Catalyzed Friedel-Crafts
Reaction of Indoles with α,β-Unsaturated Aldehydes
TFA
(0.15 mmol) was added to a solution of CaSH 1 (0.15 mmol)
in toluene (1 mL). The solution was stirred for 20 min and then
cooled to -40 ˚C. The α,β-unsaturated
aldehyde (1.5 mmol) was then added. After stirring for another 20 min,
the N-substituted indole (0.5 mmol) was added. The reaction was
stirred until complete consumption of the indoles as determined
by TLC. MeOH (2 mL) was added to the reaction mixture followed by
NaBH4 (3.0 mmol). The mixture was warmed to 0 ˚C
and stirred for 20 min. The reaction was quenched by H2O
and extracted with EtOAc. The organic solution was dried over anhyd
Na2SO4. The product 6 was
purified by silica gel chromatography (PE-EtOAc, 4:1).
The ee was determined by chiral HPLC (Chiracel AD-H) of the alcohol 6 (5% i-PrOH
in hexane
as eluent, 1 mL min-¹).
Spectroscopic
Data of Products 6 (Table 2)
Compound 6 (R² = Me): ¹H
NMR (400 MHz, CDCl3): δ = 7.74 (dd, J = 7.6, 0.8
Hz, 1 H), 7.33 (m, 4 H), 7.21 (m, 4 H), 6.96 (s, 1 H), 5.29 (s,
2 H), 3.30 (m, 2 H), 3.27 (m, 1 H), 2.08 (m, 1 H), 1.95 (m, 1H),
1.44 (d, J = 7.2
Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 138.0,
137.1, 129.0, 127.7, 127.6, 126.9, 124.6, 122.0, 121.1, 119.8, 119.1,
110.0, 61.7, 50.1, 40.6, 27.9, 22.1 ppm. HRMS (MALDI-TOF): m/z calcd for C19H22NO [M + H]+:
280.1696; found: 280.1695.
Compound 6 (R² = Et): ¹H
NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 7.6, Hz,
1 H), 7.25 (m, 4 H), 7.14 (m, 1 H), 7.06 (m, 3 H) 6.88 (s, 1 H),
5.24 (s, 2 H), 3.56 (m, 2 H), 2.93 (m, 1 H), 1.98 (m, 2 H), 1.74
(m, 2H), 0.83 (t, J = 7.0
Hz, 3 H) ppm.
Compound 6 (R² = Pr): ¹H
NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 8.0 Hz,
1 H), 7.33-7.24 (m, 4 H), 7.18 (m, 1 H), 7.17-7.06
(m, 3 H) 6.93 (s, 1 H), 5.29 (s, 2 H), 3.62 (m, 2 H), 3.05 (m, 1
H), 2.03 (m, 2 H), 1.18 (m, 2 H), 1.30 (m, 2 H), 0.88 (t, J = 7.2 Hz,
3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 138.0,
137.1, 128.9, 127.8, 127.7, 126.7, 125.6, 121.8, 119.9, 119.0, 118.9,
110.0, 61.9, 50.0, 39.0, 38.9, 33.6, 21.0, 14.4 ppm.
Compound 6 (R² = Bu): ¹H
NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 7.6 Hz,
1 H), 7.30-7.22 (m, 4 H), 7.14 (t, J = 7.6 Hz,
1 H), 7.09-7.03 (m, 3 H), 6.90 (s, 1 H), 5.27 (s, 2 H), 3.59
(m, 2 H), 3.01 (m, 1 H), 2.00 (m, 2 H), 1.78 (m, 2 H), 1.23 (m,
4 H), 0.83 (t, J = 7.2
Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 138.0,
137.1, 128.9, 127.8, 127.7, 126.7, 125.6, 121.8, 119.9, 119.0, 110.0,
61.9, 50.0, 39.0, 36.3, 33.8, 30.2, 23.0, 14.3 ppm.
Compound 6 (R² = Ph): ¹H
NMR (400 MHz, CDCl3): δ = 7.52 (m,
1 H), 7.38-7.07 (m, 12 H), 7.03 (m, 2 H), 5.30 (s, 2 H),
4.44 (t, J = 7.6
Hz, 1 H), 3.68 (m, 2 H), 2.48 (m, 1 H), 2.29 (m, 1 H) ppm. ¹³C
NMR (100 MHz, CDCl3): δ = 145.1, 138.0,
237.2, 129.0, 128.7, 128.1, 127.9, 127.8, 126.9, 126.4, 125.6, 122.1,
120.0, 119.3, 119.1, 109.9, 61.5, 50.2, 39.4, 39.0 ppm.
Compound 6 (R² = 4-ClC6H4): ¹H
NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 8.0 Hz,
1 H), 7.33-7.22 (m, 8 H), 7.15 (m, 3 H), 7.01 (m, 2 H),
5.29 (s, 2 H), 4.40 (t, J = 7.6
Hz, 1 H), 3.64 (m, 2 H), 2.43 (m, 1 H), 2.22 (m, 1 H) ppm. ¹³C
NMR (100 MHz, CDCl3): δ = 143.6, 137.8,
137.2, 131.9, 129.4, 129.0, 128.7, 127.8, 127.6, 126.8, 125.5, 122.2,
119.8, 119.4, 118.5, 110.0, 61.2, 50.2, 38.8, 38.7 ppm.
Compound 6 (R² = 4-BrC6H4): ¹H
NMR (400 MHz, CDCl3): δ = 7.40 (m,
3 H), 7.37-7.18 (m, 6 H), 7.15-7.07 (m, 3 H), 6.99
(m, 2 H), 5.28 (s, 2 H), 4.38 (t, J = 8.0
Hz, 1 H), 3.62 (m, 2 H), 2.43 (m, 1 H), 2.22 (m, 1 H) ppm. ¹³C
NMR (100 MHz, CDCl3): δ = 144.1, 137.8,
137.2, 131.7, 129.8, 129.0, 127.8, 127.6, 126.8, 125.5, 122.2, 120.0,
119.8, 119.4, 118.4, 110.0, 61.2, 50.2, 38.8, 38.7 ppm.