Synlett 2018; 29(09): 1161-1166
DOI: 10.1055/s-0036-1591961
letter
© Georg Thieme Verlag Stuttgart · New York

Remarkable Diastereoselectivity of the Thia-Michael Reaction on α,α′-Di[(E)-benzylidene]alkanones: Exclusive Formation of a meso Product

Chayan Guha
Department of Chemistry, Jadavpur University, Kolkata 700032, India   Email: [email protected]
,
Nayim Sepay
Department of Chemistry, Jadavpur University, Kolkata 700032, India   Email: [email protected]
,
Tapas Halder
Department of Chemistry, Jadavpur University, Kolkata 700032, India   Email: [email protected]
,
Asok K. Mallik*
Department of Chemistry, Jadavpur University, Kolkata 700032, India   Email: [email protected]
› Author Affiliations
Financial assistance from the DST-PURSE, UGC-CAS and UPE-II (UGC) programs, Department of Chemistry, Jadavpur University is gratefully acknowledged. C.G., N.S. and T.H. are thankful to the UGC, New Delhi for their Research Fellowships.
Further Information

Publication History

Received: 27 January 2018

Accepted after revision: 23 February 2018

Publication Date:
22 March 2018 (online)


Abstract

Thia-Michael addition of thiophenol to α,α′-di[(E)-benzyl­idene]alkanones of both cyclic (six-membered) and acyclic varieties using anhydrous K2CO3 or amberlyst-15 as catalyst has been found to be highly diastereoselective at 15 °C. A one-pot protocol was developed for such reactions by a tandem aldol-thia-Michael process. The stereochemistry of the products was confirmed by X-ray crystallographic studies and in all cases formation of a meso product was observed.

Supporting Information

 
  • References and Notes

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  • 9 See Supporting Information for details of the theoretical calculations.
  • 10 General Procedure for the Synthesis of Bis-β-aryl-β-mercaptoalkanones (3/5/8/10): α,α′-Di[(E)-benzylidene]alkanones (1/4/9, 1 mmol) were thoroughly mixed with neutral alumina (4 g) with added anhydrous K2CO3 (2 mmol) or amberlyst-15 (80 mg). The mass was cooled to 15 °C and thiophenol (2, 2 mmol) was added to keep the temperature constant. The resulting mixture was kept at 15 °C for 4 h under closed conditions. The solid was then washed thoroughly with CH2Cl2. The washings were collected, concentrated and subjected to column chromatography through silica gel using PE–EtOAc mixtures as eluents to get the bis-β-aryl-β-mercaptoalkanones (3/5/8/10). General Procedure for One-Pot Synthesis of Bis-β-aryl-β-mercaptocyclohexanones (5/8) from Cyclohexanones: A mixture of a cyclohexanone (6, 1 mmol) and aromatic aldehyde (7, 2 mmol) was thoroughly ground over neutral alumina (4 g) with added anhydrous K2CO3 (2 mmol) or amberlyst-15 (80 mg) and the resulting powder was subjected to microwave irradiation at 540 W for 5 min (120–125 °C). After cooling the mass to 15 °C, thiophenol (2, 2 mmol) was added to keep the temperature constant and the components were thoroughly mixed. The mixture was kept at 15 °C for 4 h under closed conditions. The solid was then washed thoroughly with CH2Cl2 and the concentrate of the washings was subjected to column chromatography over silica gel using PE–EtOAc mixtures as eluents to get the bis-β-aryl-β-mercaptocyclohexanone (5/8) in pure state as a single diastereomer.
  • 11 Physical and spectral data of representative compounds of the series 3, 5 and 8: Compound 3b: colourless crystals; mp 72–74 °C. IR (KBr): 1678 (C=O), 1492, 1325, 1226, 1015, 815 cm–1.1H NMR (300 MHz, CDCl3): δ = 2.28 (s, 6 H, 2 × ArMe), 2.89–2.92 (m, 4 H, 2 × CH2), 4.59 (dd, J = 8.0, 6.8 Hz, 2 H, 2 × CH), 6.97–7.02 (m, 2 × 4 H, ArH), 7.19–7.24 (m, 2 × 5 H, ArH). 13C NMR (75 MHz, CDCl3): δ = 21.1, 47.5, 49.6, 127.4, 127.5, 128.8, 129.1, 132.7, 134.2, 137.0, 137.6, 204.8. HRMS: m/z [M + Na]+ calcd for C31H30NaOS2: 505.1636; found: 505.1637. Compound 5b: colourless crystals; mp 124–126 °C. IR (KBr): 1678 (C=O), 1514, 1344, 1219, 998, 986, 822 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.66–1.69 (m, 3 H, cyclohexanone HA-3, HA-4, HA-5), 2.00 (br s, 1 H, cyclohexanone HB-4), 2.28 (s, 6 H, 2 × ArMe), 2.61 (br s, 2 H, cyclohexanone HB-3, HB-5), 2.86 (t, J = 4.5 Hz, 2 H, 2 × Hα), 4.62 (d, J = 7.5 Hz, 2 H, 2 × Hβ), 6.89 (d, J = 8.1 Hz, 4 H, ArH), 7.00 (d, J = 8.1 Hz, H, ArH), 7.12–7.23 (m, 10 H, ArH). 13C NMR (75 MHz, CDCl3): δ = 21.0, 25.4, 32.8, 52.3, 57.5, 126.8, 127.8, 128.6, 128.7, 132.1, 135.1, 136.0, 139.0, 208.4. HRMS: m/z [M + Na]+ calcd for C34H34NaOS2: 545.1933; found: 545.1949. Compound 8a: colourless crystals; mp142–144 °C. IR (KBr): 1673 (C=O), 1515, 1333, 1215, 977, 818, 782 cm–1. 1H NMR (300 MHz, CDCl3): δ = 1.08 (d, J = 6.3 Hz, 3 H, Me), 1.45–1.57 (m, 2 H, cyclohexanone HA-3, HA-5), 1.99 (br s, 1 H, cyclohexanone H-4), 2.49–2.54 (m, 2 H, cyclohexanone HΒ-3, HΒ-5), 2.91–2.96 (m, 2 H, 2 × Hα), 4.69 (d, J = 6.9 Hz, 2 H, 2 × Hβ), 7.07–7.28 (m, 20 H, ArH). 13C NMR (75 MHz, CDCl3): δ = 21.3, 32.0, 39.8, 52.6, 56.0, 126.6, 127.0, 128.0, 128.04, 128.6, 132.2, 134.8, 141.9, 208.2. HRMS: m/z [M + Na]+ calcd for C33H32NaOS2: 531.1692; found: 531.1564.