Alkylation Reactions Using a Galactose-Based β-Keto Ester Enolate and Conversion into β-C-Galactosides

Abstract

A de novo approach for the synthesis of biologically important C-galactosides has been achieved via use of an acyclic galactose-derived β-keto ester. The β-keto ester enolate serves as a C-nucleophile and reacts with primary alkyl halides and Michael acceptors to generate alkylation products that can be converted into β-C-galactosides and C-disaccharide mimics with high stereoselectivity.

Key words

de novo approach - C-galactosides - C-nucleophile

References and Notes

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15

Procedure for the Synthesis of β-Keto Ester 3 In an inert atmosphere a solution of ketose 2 (150 mg, 0.23 mmol) in dry DMF (5 mL) was cooled to 0 ˚C and a suspension of NaH (60 wt% in oil, 137 mg, 15 equiv) was added slowly over 5 min. After 30 min at 0 ˚C, allyl chloride (562 µL, 30 equiv) was added. The reaction was stirred at r.t. for 1 h, cooled to 0 ˚C, and quenched by slow addition to a mixture of ice and sat. NH₄CI soln (10 mL). The resultant mixture was extracted twice with EtOAc (2 × 15 mL), and the combined extracts were dried over Na₂SO₄ and concentrated in vacuo. Flash column chromatography, with EtOAc-hexane (1:9) as eluent, gave β-keto ester 3 (138 mg, 87% yield) as an oil. ^¹³C NMR (75 MHz, CDCl₃): δ = 28.1 (Boc), 47.9, 69.9, 72.0, 73.1, 73.3, 73.4, 74.1, 77.8, 78.4, 79.5, 81.7 (quart. C, Boc), 84.4, 116.7, 127.5-128.5 (arom.), 135.3 (=CH₂), 137.5, 138.0, 138.2, 138.4, 166.9, 204.4. MS (ES⁺): m/z = 717.31 [M + Na]⁺. Anal. Calcd for C₄₃H₅₀O₈: C, 74.33; H, 7.25. Found: C, 74.41; H, 7.36.