Simple and Efficient Preparation of Reagents for Thiopyran Introduction:
Methyl Tetrahydro-4-oxo-2H-thiopyran-3-carboxylate, Tetrahydro-4H-thiopyran-4-one, and 3,6-Dihydro-4-trimethylsilyloxy-2H-thiopyran

Abstract

Tetrahydro-4H-thiopyran-4-one was prepared in >75% yield by treatment of dimethyl 3,3′-thiobispropanoate with NaOMe (generated in situ) in THF solution and decarboxylation of the resulting methyl tetrahydro-4-oxo-2H-thiopyran-3-carboxylate in refluxing 10% aqueous H₂SO₄. Reaction of tetrahydro-4H-thiopyran-4-one with Me₃SiCl and Et₃N in CHCl₃ gave the corresponding trimethylsilyl enol ether in near quantitative yield. The prepared reagents are useful for the synthesis of thiopyran-containing compounds.

tetrahydro-4H-thiopyran-4-one - 4-thianone - heterocyclic ketone - Dieckmann cyclization - thiopyran synthesis

References

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<A NAME="RM06106SS-12">12</A>

A reaction using 1.1 equiv of NaOMe did not go to completion within 5 h (ca. 90% conversion).

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<A NAME="RM06106SS-15">15</A>

Na metal was cut into pieces weighing ca. 50-100 mg (3-5 mm per side). The rate of Na consumption depends on the size of pieces; with larger pieces, more time is required to reach 90% conversion.

<A NAME="RM06106SS-16">16</A>

A few specks of Na metal may remain at this point.

<A NAME="RM06106SS-17">17</A>

The presence of small amounts of 1 (<1%) and its corresponding half-acid (1-2%) were detected by ¹³C NMR and confirmed by spiking with authentic samples.