Heterocycles chromanones

The scarcity of reviews1 and recent interest in thiochromanones and related compounds calls for a comprehensive summary of this area of heterocyclic chemistry. The apparent similarity between these systems and the naturally occurring chromanones, chromones (flavones), chromenes, etc., is responsible for the continued importance of these sulfur heterocycles. Chemical Abstracts (through November, 1973) has been employed as the principal reference source and nomenclature guide for this review. 

Thus, according to Dupayrat,7 the basic heterocycle is chromeno-[3, 4-6]chromene (11). Consequently, rotenoids are furo[2,3-A]chromano-[3,4-6]chromanones (12), and rotenone (13) is 2-isopropenyl-8,9-dime-thoxy-6-oxo-l,2,6a,12a-tetrahydrofuro[2,3-/i]chromeno[3,4-6]chromene. On the other hand, compound 11 has been given a global name, rotox-ene,14,15 which makes the nomenclature more manageable, but does not seem to have been generally accepted. The nomenclature here adopted for rotenoids is that of Chemical Abstracts unfortunately this has... 

The present volume encompasses a wide range of heterocyclic chemistry. Syntheses of heterocycles from thioureas are reviewed by T. S. Criffin, T. S. Woods, and 1). L. Klayman, while S. W. Schneller describes the chemistry of benzothiins and their derivatives (thiochromans, thiochromones, and thio-chromanones). Developments in chrom-3-ene chemistry are reviewed by L. Merlini. F. D. Popp contributes a chapter on the isatins. A discussion of theoretical aspects of the tautomerism of pyrimidines, by J. S. Kwiatkowski and B. Pullman, follows up a corresponding earlier contribution (Vol. 13) on tautomeric purines. In the final chapter P. and D. Cagniant describe the natural occurrence and synthesis of the benzofurans. 

The compounds covered in this section include dihydropyranones, tetrahydropyranones and their benzologues (dihydrocoumarins, chromanones and isochromanones). The area of greatest interest is undoubtedly the chromanones because of their relationship to a number of natural products and presumably also because of their ease of formation, stability and value as precursors of other heterocycles. Tetrahydropyran-2-ones comprise one of those nebulous areas of heterocyclic chemistry and usually feature in text books as 5-lactones under derivatives of hydroxy acids. 

Chemistry of Heterocyclic Compounds 1977 , Volume 31 (Chromenes, Chromanones, and Chromones). 

The same reaction has been also carried out with heterocyclic aminomethyleneketone derivatives of, e.g., 4-pyranones273, chromanones and derivatives and 4-piperidones276 (equation 202). A useful dienophile is dichloroketene, produced from dichloroacetyl chloride and triethylamine. It enables the enaminone oxygen to be incorporated into the functional group of a lactone instead of a sultone (equation 202). 

Enders D, Niemeier O, Raabe G (2006d) Asymmetric synthesis of chromanones via N-heterocyclic carbene catalyzed intramolecular crossed-benzoin reactions. Synlett 2006 2431... 

With respect to the application of asymmetric carbene catalysis as a tool for enantioselective synthesis, the last decade s major success is based on substantial improvements in catalyst development. Early reports dealt with implementing chirality in thiazolium scaffolds (Sheehan and Hunneman 1966 Sheehan and Hara 1974 Dvorak and Rawal 1998), but their catalytic performance suffered from either low yields or low ee-values. In this regard, the investigation of triazole heterocycles as an alternative core structure (Enders et al. 1995) has played a crucial role to provide heterazolium precatalysts improving both asymmetric benzoin and Stetter reactions. An intramolecular Stetter reaction yielding chromanones upon cyclization of salicylaldehyde-derived substrates is commonly used as a benchmark reaction to compare catalyst efficiency (Scheme 1 Ciganek 1995 Enders et al. 1996 Kerr et al. 2002 Kerr and Rovis 2004). 

Oxidation of chroman-4-one and its thio analogue with Mn(OAc)3 gives the 3-acetates and subsequent basic hydrolysis yields the 3-hydroxychroman-4-one. Enzymatic hydrolysis of the 0-heterocycle using Amano PS lipase in a phosphate buffer selectively cleaved the (+)-isomer <03TA1489>. Enol ethers derived from chroman-4-one are converted into the 3-hydroxy-chromanone with high enantioselectivity, optimal with the pentyl ether, using a modified Sharpless asymmetric dihydroxylation reaction <03JOC8088>. 

Recently, a novel chiral N-heterocyclic carbene G2 derived from (-)-p-pinene was synthesised and proved to be an efficient catalyst for the intramolecular Stetter reaction. A series of substrates worked well affording 4-chromanones 37 in good yields and with high enantiomeric excess (Scheme 20.18). 

Other heterocyclic systems formed via Buchner reactions include cycloheptafuranones 69. Thus diazoketones 67 with a-phenoxy substituents undergo cyclization catalyzed by copper(II) bis(hexafluoroacetonate) to furnish mixtures of cycloheptafuranones 69 and chromanones 70. The product compositions depend on substituents in the precursors. These cycloheptafuranones rearomatize readily to chromanones 70 upon contact with silica gel. 

As shown in Scheme 2, our first approach for construction of the labile iso-chromanone core 3 relied on an innovative orf/io-lithiation strategy. It was envisioned that in conjunction with an appropriate chiral-directing group, a suitable electrophile (5) might be introduced in the orf/io-position of the meta-lated aromatic 4. The resulting product would then be further transformed into the desired heterocycle 3. Notably, this route is very flexible by allowing the addition of various electrophiles in a modular fashion. Also, it starts from a 3-methylsalicylic acid derivative (4) that already contains almost the complete aromatic substitution pattern of the ajudazols. 

Gao, Y., Ren, Q., Wu, H., Li, M., Wang, J. (2010). Enantioselective heterocyclic synthesis of spiro chromanone-thiochroman complexes catalyzed by a bifunctional indane catalyst. Chemical Communications, 46, 9232-9234. 

---