Preparation of New Chiral Building Blocks by a Mukaiyama–Michael Reaction of 2-(Phenylsulfonyl)cyclopent-2-en-1-one

Abstract

A highly enantio- and diastereoselective Mukaiyama–­Michael reaction of 2-(phenylsulfonyl)cyclopent-2-en-1-one by using an enol silane of tert-butyl thiopropionate is described. The product was formed in 87% yield with a dr of 27:1 and 91% ee under stoichiometric conditions, whereas the yield, dr, and ee were 89%, 49:1, and 88% ee, respectively, under catalytic conditions. A highly stereoselective epimerization of the product of the Mukaiyama–Michael reaction which proceeds in 77% yield with a dr of 22:1 is also described. Because both enantiomers of the ligand for this Mukaiyama–Michael reaction are available, a method for the synthesis of all four stereoisomers of the product as useful chiral building blocks has been established.

Key words

Mukaiyama–Michael reaction - asymmetric catalysis - enantioselectivity - diastereoselectivity - chiral building blocks - phenylsulfones

Publication History

Received: 13 December 2022

Accepted after revision: 08 February 2023

Accepted Manuscript online:
08 February 2023

Article published online:
02 March 2023

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• 17 Compound 9f A mixture of Cu(OTf)₂ (4.5 mg, 0.0124 mmol), L3 (6.5 mg, 0.0155 mmol), and 3 Å MS (38.7 mg) in 2:1 toluene–DCM (0.290 mL) was stirred at rt for 1.5 h. A solution of 5 (13.2 mg, 0.0594 mmol) in 2:1 toluene–DCM (0.600 mL) was added and the mixture was stirred at rt for 1.5 h. A solution of 8f (17.7 mg, 0.0810 mmol) in 2:1 toluene–DCM (0.300 mL) was added at –60 °C, and the mixture was stirred at –60 °C for 41.5 h. The reaction was quenched with sat. aq NaHCO₃ (2.0 mL) and the mixture was filtered. The aqueous layer was extracted with EtOAc (3 × 5 mL), and the combined organic layer was washed with H₂O (5 mL) and brine (5 mL) then dried (Na₂SO₄) and concentrated under reduced pressure. The residue was purified by flash column chromatography [silica gel, hexane–EtOAc (6:1)] to afford 9f containing inseparable L3 as a white solid; yield: 26.0 mg [0.0531 mmol, 89% (calcd based on ¹H NMR)]; R_f = 0.70 (hexane–EtOAc, 2:3). [α]_D ²¹ –55 (c 0.65, DCM). IR (ATR): 1747, 1666, 1310, 1151, 1084, 1063, 970, 755, 729, 686, 621, 586, 555, 533, 494 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.86 (d, J = 7.5 Hz, 2 H), 7.70 (t, J = 7.5 Hz, 1 H), 7.58 (dd, J = 7.5, 7.5 Hz, 2 H), 3.83 (d, J = 5.0 Hz, 1 H), 3.25 (ddd, J = 8.0, 5.5, 5.0 Hz, 1 H), 2.90 (ddd, J = 7.5, 7.0 , 5.0 Hz, 1 H), 2.48–2.38 (m, 1 H), 2.36–2.25 (m, 1 H), 1.88–1.79 (m, 1 H), 1.43 (s, 9 H), 1.18 (d, J = 7.5 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 206.4, 202.8, 137.8, 134.3, 129.2, 71.8, 50.5, 48.6, 40.5, 37.7, 29.7, 23.6, 14.6. HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₄NaO₄S₂: 391.1014; found: 391.1007.
• 18 CCDC 2235289 contains the supplementary crystallographic data for compound 9f′. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
• 19 Sugiyama R, Nakada M. Synlett 2023; in press DOI: 10.1055/a-2017-3636.
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