Reactions at C3 with Electrophiles

Introduction of a formyl group at C3 on methyl ethers can be performed by direct treatment with dichloromethyl methyl ether under titanium tetrachloride catalysis (82CJC2821), as in the conversion of 153 into 154 or by modification of the side chain of pyrone 2, including an oxidation step on methyl ether 156, to afford 157 (87TL1175). 3-Formyl-4-hydroxy-6-methyl- 

2-pyrone (159) has been prepared from 1 by reaction with triethyl orthoformate and aniline, followed by hydrolysis of 158 (75M963). 

The obvious alternative based on the reaction of 1 with alcohols is of limited value and has been applied to alcohols that are precursors of stabilized carbenium ions, both under protic (83AP988) and cobalt(II) chloride catalysis (83MI1) and under purely thermal conditions (59CB982). This last paper describes an unusual case of carbon-carbon formation, although in low yield, under Sandmeyer conditions at C3 of pyrone 1. 

The Michael addition, a reversible reaction, produces alkylation at C3 [83AP988 86JCR(S)374] as exemplified by the formation of 166, which can further be elaborated to 167 and 168 [86JCR(S)374]. A preparation of the natural product 94 involves hydrogenation of 158 [82ZN B) 105]. 

Branched radicals can be introduced at C3 by Claisen rearrangement of enol ethers. This has been used to prepare 170 in one step of the synthesis of Mundulea lactone (107) (67CC577). Further examples can be found (88JOC5328). 

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