Chrom-3-enes

Considerable interest has followed from the early work on precocenes 1 and 2 (ref. 37), compounds having antijuvenile hormone activity and in consequence a number of syntheses have been developed. In the original work known methodology (ref. 85) was used. Thus, the reaction of 3-methoxyphenol and of 

4-dimethoxyphenol (R = OMe) with 3-methylbut-2-enoic acid in the presence of polyphosphoric acid led to the respective 2,2-dimethylchromones which were reduced by lithium aluminium hydride and then dehydrated to afford the two final products. The procedure has been improved (ref. 86) by the reaction of resorcinol and of 3,4-dihydroxyphenol with the same acid in phosphorus oxychloride containing zinc chloride and 5% water to afford the respective chromones in 79-82% yield. Methylation with methyl iodide in DMF containing potassium carbonate gave the methyl ethers (R = OMe) which upon reduction in methanol with sodium borohydride gave the corresponding alcohols. Dehydration with 4M hydrochloric acid completed the syntheses. 

A direct procedure, partly based in earlier knowledge, giving the chrom-3-ene (2H-benzo[b]pyran) structure in one-step has been referred to earlier. In this method titanium or magnesium phenolates formed from the phenol with the metal ethoxide and removal of ethanol, are then reacted with a,p-unsaturated aldehydes or ketones in toluene solution at 110 C over 8 hours (ref. 40). In this way precocene 2 was derived from the reaction of the magnesium salt of 

4- dimethoxyphenol with 3-methylbut-2-enal in 80% yield (98% based on the 

4- dimethoxyphenol consumed). Tin(IV) and aluminium phenolates could also be employed and regiochemical control was high with more than 90% selectivity, through reaction at the 4-position in resorcinolic systems. 

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The aim of this review is to survey the advances in the chemistry of chrom-3-enes (2 -l-benzopyratis, chroin-/l3-eiies, a-chromenes)1 in the last decade. This subject was previously summarized by Wawzonek2 in 1951. A brief but clear treatment of chrom-3-ene chemistry can be found in Dean s book3 (1963), where a detailed account is given of all the natural products known at that time. A section of a recent book on the synthesis of natural compounds has been dedicated to chromenes.4... 

Although the name 111-1 -benzopyran is preferred by Chemical Abstracts, the more common nomenclature chrom-3-ene will be used throughout this review. 

The nuclear magnetic resonance (NMR) spectrum of chrom-3-ene (1) has been measured13 and the sign of coupling constants between protons on the hetero ring obtained from a study of double quantum transitions.13 An inter-ring coupling (J4 8) has been detected.14-16 In... 

Much progress has been made in the last ten years in the synthesis of chrom-3-enes. Most of the activity has been stimulated by the discovery of new natural products and by the suggestions of possible biosynthetic pathways (see Section III). For results prior to 1963, the reader should consult Dean s book3 and Wawzonek s review.2... 

Chromenes are easily obtained by dehydration of 4-chromanols (24), in their turn readily available by reduction of 4-chromanones (23). The parent compound chrom-3-ene has been prepared by this method92 in 75-80% yield, via Meerwein-Ponndorf reduction and dehydration by azeotropic distillation over CuS04. Other reducing agents are metal... 

Nucleophilic addition to benzopyrylium salts is another route to chromenes, but the attack may occur at the positions 2 or 4, thus giving rise to chrom-3-enes (30) or chrom-2-enes (31). Thus NaBH4 reduces simple flavylium salts to flav-2-ene121 (which, in its turn, behaves as a nucleophile and gives rise to dimeric products110) whereas 3-substituted... 

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