Rhodium Carbenoid Induced [1,2]-Migration in an l-Lyxo-Configured α-Diazo β-Keto Ester: Synthesis of a New Griseolic Acid Analogue

Abstract

An appropriately substituted α-diazo β-keto ester, prepared from d-glucose, on treatment with a catalytic amount of dirhodium tetraacetate gave a strained 1,5-dioxabicyclo[3.3.0]octane ring system with concomitant diastereoselective formation of a quaternary carbon substituted with both an ethoxycarbonyl group and a 2-ethoxy-2-oxoethyl group; the product is a key intermediate in the synthesis of a new griseolic acid analogue.

Key words

carbenoids - carbohydrates - carboxylic acids - diazo compounds - oxygen heterocycles

References

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11

Selective hydrolysis of the 5,6-O-isopropylidene group in 3c was possible probably because of the α-orientation of the 5,6-diol in the furanose ring; transfer of a proton from the protonated oxygen at the C-6 carbon to the C-1 acetonide facilitates the 1,2-acetonide deprotection competitively. Attempts with various other acidic reagents, such as 10% H₂SO₄, CuCl₂˙2H₂O, 30% HClO₄, or acidic resin (Indion 140), failed to give good yields.

13

The unstable nature of compound 7 precluded further characterization. At this stage, attempts were made to convert the keto compound 7 into one with an olefinic functionality at the ring junction. Thus, attempts at the reaction of 7 by using the Shapiro protocol (SO₂Cl₂ and POCl₃) led to a complex mixture. Attempts to activate the hydroxyl functionality by using mesyl chloride and subsequent treatment with base under reflux were also unsuccessful.

14

Our attempts to isolate the other diastereomer (C-5β-OH) in a pure form were unsuccessful.

15

In the ^¹H NMR spectrum of 9, the C-5 appeared at δ = 5. 5 as a doublet (J _5,4 = 5.00 Hz). In 1D NOSEY irradiation, one of the C-7 methylene protons at δ = 2.48 showed a NOE with H-3, H-4, H-5, indicating a syn-relationship between the
-CCH₂COOEt group and the sugar ring protons, and confirming our earlier assignment.

16

The ^¹H NMR spectrum of 10 shows the presence of an anomeric mixture in the ratio 1:15 in favor of the β-anomer.