Pyrans vinylogous

The alternative structural situation of an exocyclic methylene group in conjugation with a ring oxygen is found in methylene-4-pyrans (vinylogous pyrones), in which a 4-pyrone-like resonance [230] occurs. These compounds are little known. Their synthesis... 

Some representatives of this group occur as natural products, including kojic acid (4.1), which can be isolated from the Aspergillus mould used in the manufacture of sake from rice. Like pyran-2-ones, these compounds show little aromatic character and are best considered as vinylogous lactones (Scheme 4.9), rather than as unsaturated ketones. 

Usually, the a-pyranic addition products (3) cannot be isolated because they isomerize immediately in a thermally allowed electrocyclic process affording acyclic dienones (4), which in many cases react further. Therefore, pyrylium salts 2A react with most nucleophiles as if they had the electronic structure 2B, and thus the pyrylium cation behaves as a useful synthon, namely the last vinylog in the series of acyl halides (Cj synthon) - p-halovinyl ketones (C3 synthon) - pyrylium (C5 synthon) [50, 51],... 

As shown in Scheme 36,2,2-disubstituted-5-alkyl-3(2//)-furanones also undergo -y-alkylation via their extended dienolate intermediates (75). Similarly, 4-isopropyl-6-methyl-(2H)-pyran-2-one, which may be regarded as a vinylogous S-alkyl-3(2//)-furanone, was deprotonated and alkylated at the methyl group. ... 

The Cu-promoted enantioselective oxidative dearomatisation of aUcynylbenzaldehydes followed by a cycloisomerisation leads to azaphilones, fused 4//-pyrans (Scheme 1) <05JA9342>, while an alternative synthesis involves oxidation of a 1/7-benzopyrylium salt derived from a substituted benzaldehyde (Scheme 2) <05JOC4585>. Treatment of azaphilones with primary amines results in cleavage of the pyran ring and the formation of vinylogous y-pyridones. 

Danishefsky prepared the furanophane 184 and converted it to hydropyrone 185 through a directed epoxidation with DMDO. Diastereoselective addition of methyllithium was followed by an acid catalyzed isomerization to the furanoside 186. Vinylogous aldol addition of a silyloxy furan to an imine gave 189 that was easily isomerized to the azacycle 190. Another general strategy to prepare pyran derivatives is a cycloaddition/fragmentation route involving an oxabicyclo[3.2.1]octane intermediate (Scheme 24). 

A selective method for benzylic metalation of o-, m-, and p-substituted toluenes has been reported using BuLi/f-BuOKVTMP and rationalized by the ability of the mixed metal amide base to facilitate an anion migration from the kinetic (o-aryl) to the benzylic metalation site. Reaction of 2-(l-phenylethylidene)malononitrile and 2,2,2-trifluoro-1 -phenylethanone gives (2 ,4 )-2-cyano-6,6,6-trifluoro-3,5-diphenyl-hexa-2,4-dienamide via a vinylogous aldol reaction followed by rearrangement of the 2/f-pyran intermediate (Scheme 52). °°... 

Finally, the spontaneous electrocyclic ring opening of pyran derivatives (obtained by a vinylogous aldol reaction between vinyl malononitriles and aldehydes) into dienamides is to be mentioned in this section [97]. 

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