Grignard reagents with pyrylium salts

The tenth volume of this serial publication comprises six chapters, four of which deal with the general chemistry of a specific group of heterocyclic compounds pyridopyrimidines (W. J. Irwin and D. G. VVibberley), benzofuroxans (A. J. Boulton and P. B. Ghosh), isoindoles (J. D. White and M. E. Mann), and pyrylium salts (A. T. Balaban, W. Schroth, and G. Fischer). The remaining chapters are concerned with indole Grignard reagents (R. A. Heacock and S. Kasparek) and with cyclic hydroxamic acids (J. B. Bapat, D. St. C. Black, and R. C. Brown).The international flavor of the publication is preserved our contributors come from six countries in three continents. 

Grignard reagents add directly at C-4 here subsequent ring opening is not an option, but when treated with strong acid the adducts are converted into pyrylium salts (Scheme 4.10b). 

The reaction of pyrylium salts with Grignard reagents seems a generally applicable method for the preparation of substituted 2H- and 4//-pyrans. The syntheses of 165 according to Eq. (8) was the first in this field.233,234... 

The regioselectivity in the Grignard reactions of tetrasubstituted pyrylium salts is the consequence of simultaneous effects of substitution patterns in both the substrate and the reagent. Thus the reaction of MeMgl with 2,3,4,6-or 2,3,5,6-tetramethylpyrylium ions provide mixtures of isomeric 2//-pyrans 187 and 188 in the ratio 91 9 or of 2//-pyran 189 and 4i/-pyran 190 in the ratio 48 52, respectively.237... 

Pyran-4-ones with Grignard reagents give pseudo-bases which form the pyrylium salts with acid, e.g. (288) - (289). 

The reaction of pyrylium salts with Grignard reagents or organolithium compounds leads to the pseudobase by attack at C-2 (59CB2042). A similar reaction occurs with the anions derived from malononitrile and diethyl malonate, although the pyran derivatives were not always isolated (59CB2046). 

The anions derived from various active methylene compounds react with 2,6-disubstituted pyrylium salts to form 4-substituted 4//-pyrans (57AG720, 59CB46). Grignard reagents react to give similar compounds (60AG777). 

Pyrones also add Grignard nucleophiles at the carbonyl carbon, C-4 dehydration of the inunediate tertiary alcohol product with mineral acid provides an important route to 4-mono-substituted pyrylium salts." More vigorous conditions lead to the reaction of both 2- and 4-pyrones with two mole equivalents of organometallic reagent and the formation of 2,2-disubstituted-2H- and 4,4-disubstituted-4//-pyrans, respectively." Perhaps surprisingly, hydride (lithium aluminium hydride) addition to 4,6-dimethyl-2-pyrone takes place, in contrast, at C-b." ... 

Conversion of pyrylium salts with organolithium and Grignard reagents to pyrans via reductive alkylation or arylation has been enriched by applications of organocopper and other organometallic compounds as well as by photochemical activation. Several new studies with anions of C-acids have been published as well. 

Substituted pyrylium salts are obtained from Grignard reagents and 4/f-pyran-4-ones in a 1 1 proportion, followed by treatment with strong acid. Excess of RMgX, however, yields 4,4-disubstituted 4//-pyrans ... 

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