.
Typical procedure for ruthenium-catalyzed aldol reaction
A mixture of aldehyde (1 mmol), ketone (3 mmol), RuCl3.nH2O(0.02 mmol) and KOH (28 mg, 0.5 mmol) was stirred at 15 °C and monitored by TLC. After the indicated reaction time, the reaction mixture was purified by thin layer chromatography (silica gel, EtOAc-petroleum ether, 4:12) providing the aldol adduct.
Selected Spectral Data of the Products
Product (3aa)
Yellow oil; FT-IR (neat) (υmax/cm-1): 1666, 3415. Only syn isomer was isolated. 1H NMR (500 MHz, CDCl3): δH(ppm) 1.69-2.65 (m, 7H), 2.52 (s, 3H), 3.03 (d, J = 3.2 Hz, OH), 5.39 (m, 1H), 7.28 (m, 4H). 13C NMR (125 MHz, CDCl3): δC(ppm) 12.2, 14.0, 14.9, 41.1, 58.1, 72.2, 126.5, 128.5, 133.5, 135.2, 218.4. Anal Calcd for C13H16O2S (236): C, 66.10; H, 6.77; S, 13.55. Found: C, 66.10; H, 6.79; S, 13.56.
Table 1: Ruthenium-catalyzed cross aldol reactions of aldehydes with cycloalkanones 3aa-ec.
aAll products were characterized by 1H NMR, 13C NMR and IR. b Yields after purification by chromatography. c Identified by comparison with authentic sample.38
I t is a well understood phenomenon that the lower values of the 1H NMR coupling constants of the carbinol protons than 1 Hz, for example 3cc, along with very weak correlation between the 1-H and 2-H (Figure 1) in the NOESY spectrum clearly indicate the relative stereochemistry of the aldol adduct in favor of the syn geometry. Also, in the IR spectrum of 3cc, the broad band of OH was observed with a maximum at 3500 cm-1, which indicates the existence of hydrogen bonding of aldol adduct (Figure 2). In fact, the structure has been fixed in a special stereochemistry which dominated by hydrogen bonding observed in IR spectra and the tendency to minimize the steric crowding between the 5-Methylthiophen-2-yl and cycloheptanone rings. These results illuminate that 1-C, 2-C, 1-H and 2-H has the same chemical environment, that is to say 3cc is exclusively of syn stereochemistry.
Product (3cc)
Yellow oil; FT-IR (neat) (υmax/cm-1): 1674, 3465. Only syn isomer was isolated. 1H NMR (500 MHz, CDCl3): δH(ppm) 2.92-1.54 (m, 11H), 2.44 (s, 3H), 3.37 (d, J = 3.9 Hz, OH), 5.25 (s, 1H), 6.60 (d, J = 2.4 Hz, 1H), 6.72 (d, J = 3.2 Hz, 1H). 13C NMR (125 MHz, CDCl3): δC(ppm) 15.2, 23.6, 25.3, 28.4, 28.6, 44.0, 57.8, 71.5, 124.5, 124.6, 138.6, 143.3, 217.2. Anal Calcd for C13H18O2S (238): C, 65.54; H, 7.56; S, 13.44. Found: C, 65.53; H, 7.56; S, 13.44.
Keshavarz E, Tabatabaeian K, Mamaghani M, Mahmoodi N. O. Surprises in the Study of Ruthenium-catalyzed Stereo- and Chemoselective Aldolizations. Orient J Chem 2015;31(4).
KEYWORDS: catalytic aldol reaction; diastereoselective aldolization; green synthesis
/////////
Typical procedure for ruthenium-catalyzed aldol reaction
A mixture of aldehyde (1 mmol), ketone (3 mmol), RuCl3.nH2O(0.02 mmol) and KOH (28 mg, 0.5 mmol) was stirred at 15 °C and monitored by TLC. After the indicated reaction time, the reaction mixture was purified by thin layer chromatography (silica gel, EtOAc-petroleum ether, 4:12) providing the aldol adduct.
Selected Spectral Data of the Products
Product (3aa)
Yellow oil; FT-IR (neat) (υmax/cm-1): 1666, 3415. Only syn isomer was isolated. 1H NMR (500 MHz, CDCl3): δH(ppm) 1.69-2.65 (m, 7H), 2.52 (s, 3H), 3.03 (d, J = 3.2 Hz, OH), 5.39 (m, 1H), 7.28 (m, 4H). 13C NMR (125 MHz, CDCl3): δC(ppm) 12.2, 14.0, 14.9, 41.1, 58.1, 72.2, 126.5, 128.5, 133.5, 135.2, 218.4. Anal Calcd for C13H16O2S (236): C, 66.10; H, 6.77; S, 13.55. Found: C, 66.10; H, 6.79; S, 13.56.
Table 1: Ruthenium-catalyzed cross aldol reactions of aldehydes with cycloalkanones 3aa-ec.
Entrya | R | Aldol | Yield (%)b | Time (h) |
1 | 1a 4-MeSC6H4 | 3aa | 81 | 5 |
2 | 1b 3-Methylthiophen-2-yl | 3ba | 86 | 1.5 |
3 | 1c 5-Methylthiophen-2-yl | 3ca | 83 | 1 |
4 | 1d Thiophen-2-yl | 3da | 91 | 3 |
5 | 1a 4-MeSC6H4 | 3ab | 79 | 4.5 |
6 | 1b 3-Methylthiophen-2-yl | 3bb | 76 | 2.5 |
7 | 1c 5-Methylthiophen-2-yl | 3cb | 77 | 3 |
8 | 1a 4-MeSC6H4 | 3ac | 72 | 4.5 |
9 | 1b 3-Methylthiophen-2-yl | 3bc | 80 | 2.5 |
10 | 1c 5-Methylthiophen-2-yl | 3cc | 78 | 2.5 |
11 12c | 1d Thiophen-2-yl 1e 4-NO2C6H4 | 3dc 3ec | 73 55 | 2 5 |
I t is a well understood phenomenon that the lower values of the 1H NMR coupling constants of the carbinol protons than 1 Hz, for example 3cc, along with very weak correlation between the 1-H and 2-H (Figure 1) in the NOESY spectrum clearly indicate the relative stereochemistry of the aldol adduct in favor of the syn geometry. Also, in the IR spectrum of 3cc, the broad band of OH was observed with a maximum at 3500 cm-1, which indicates the existence of hydrogen bonding of aldol adduct (Figure 2). In fact, the structure has been fixed in a special stereochemistry which dominated by hydrogen bonding observed in IR spectra and the tendency to minimize the steric crowding between the 5-Methylthiophen-2-yl and cycloheptanone rings. These results illuminate that 1-C, 2-C, 1-H and 2-H has the same chemical environment, that is to say 3cc is exclusively of syn stereochemistry.
Product (3cc)
Yellow oil; FT-IR (neat) (υmax/cm-1): 1674, 3465. Only syn isomer was isolated. 1H NMR (500 MHz, CDCl3): δH(ppm) 2.92-1.54 (m, 11H), 2.44 (s, 3H), 3.37 (d, J = 3.9 Hz, OH), 5.25 (s, 1H), 6.60 (d, J = 2.4 Hz, 1H), 6.72 (d, J = 3.2 Hz, 1H). 13C NMR (125 MHz, CDCl3): δC(ppm) 15.2, 23.6, 25.3, 28.4, 28.6, 44.0, 57.8, 71.5, 124.5, 124.6, 138.6, 143.3, 217.2. Anal Calcd for C13H18O2S (238): C, 65.54; H, 7.56; S, 13.44. Found: C, 65.53; H, 7.56; S, 13.44.
Keshavarz E, Tabatabaeian K, Mamaghani M, Mahmoodi N. O. Surprises in the Study of Ruthenium-catalyzed Stereo- and Chemoselective Aldolizations. Orient J Chem 2015;31(4).
Elahe Keshavarz,1,* Khalil Tabatabaeian2, Manouchehr Mamaghani2 and Nosrat O. Mahmoodi2
1Department of Sciences, Farhangian University, P.O. Box 1998963341, Rasht, Iran.
2Department of Chemistry, Faculty of Sciences, Guilan University, P.O. Box 41335-1914, Rasht, Iran.
Corresponding Author E-Mail: keshavarz@guilan.ac.ir
ABSTRACT:
A convenient and diastereoselective method was developed for
the synthesis of aldol derivatives in the presence of a catalytic amount
of RuCl3.nH2O under solvent-free conditions.
Aldol adducts were obtained in good yields and with high
chemoselectivity in short reaction times. In this protocol, aromatic
and heteroaromatic aldehydes readily participate as electrophilic
cross-aldol partners with a range of cycloalkanones as ketone donors.KEYWORDS: catalytic aldol reaction; diastereoselective aldolization; green synthesis
/////////