3-Phenylprop-2-Enal → (3S)-3-(1-Methyl-1H-indol-3-yl)-3-phenylpropanal

HRID 1837848Notes

Reaction equation

HRID 1837848 reaction equation
[CH:1](=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13]1.C(O)(C(F)(F)F)=O>C(Cl)Cl.C(O)(C)C>[CH3:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C@H:3]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:2][CH:1]=[O:10])=[CH:13]1

Participants

6

Reactant 3

HCID 3073-Phenylprop-2-EnalHCID 6422Trifluoroacetic acidHCID 117811-Methylindole

Product 1

HCID 16217418(3S)-3-(1-Methyl-1H-indol-3-yl)-3-phenylpropanalYield 84%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

Prepared according to the general procedure from cinnamaldehyde (190 μL, 1.50 mmol), 1-methyl-1H-indole (64 μL, 0.50 mmol), TFA (7.7 μL, 0.10 mmol) and (2S,5S)-5-benzyl-2-tert-butyl-3-imidazolidin-4-one (24.6 mg, 0.100 mmol) in CH2Cl2 (0.85 mL) and isopropanol (0.15 mL) at −55° C. for 45 h to provide, after silica gel chromatography (10:90 EtOAc/hexanes), the title compound as a colorless oil (110 mg, 84% yield, 90% ee). IR (film) 3051, 3026, 2945, 2888, 2822, 2733, 1722, 1616, 1604, 1547, 1474, 1429, 1376, 1331, 1245, 1225, 1156, 1131, 1013, 765, 740, 700 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.76 (dd, J=2.4, 2.4 Hz, 1H, CHO), 7.43 (dt, J=0.9, 8.1 Hz, 1H, ArH), 7.36-7.28 (m, 7H, ArH), 7.04 (ddd, J=1.2, 6.9, 8.1 Hz, 1H, ArH), 6.88 (s, 1H, NCH), 4.88 (t, J=7.5 Hz, 1H, ArCH), 3.76 (s, 3H, NCH3), 3.22 (ddd, J=2.7, 8.4, 16.5 Hz, 1H, CH2CO); 3.10 (ddd, J=2.7, 8.4, 16.5 Hz, 1H, CH2CO); 13C NMR (75 MHz, CDCl3) δ 201.8, 143.5, 137.3, 128.6, 127.6, 126.8, 126.6, 126.4, 121.9, 119.4, 119.0, 116.6, 109.3, 50.0, 37.4, 32.9; HRMS (CI) exact mass calcd for (C15H17NO) requires m/z 263.1310, found m/z 263.1306. [α]D=+30.9 (CHCl3). The enantiomeric ratio was determined by HPLC analysis of the alcohol, obtained by NaBH4 reduction of the aldehyde, using a Chiracel AD and AD guard column (3:97 ethanol/hexanes, 1 mL/min); S isomer tr=48.5 min and R isomer tr=38.9 min.

Workup

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Sources & evidence

ORD record
ord-2a1da2a95a77486786bd91ce405398f1
Source dataset
uspto-grants-2004_08
Patent number
US06784323B2

Reaction notes

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