Pyrone-3 -carboxylate synthesis

Bromo-2-pyrone is not only a valuable precursor for the synthesis of various 3-substituted 2-pyrones,7 but it is also a reactive unsymmetrical diene.8 3-Bromo-2-pyrone undergoes Diels-Alder cycloadditions with a regioselectivity and stereoselectivity that is superior to that of 2-pyrone. Furthermore, 3-bromo-2-pyrone is a chameleon (i.e., ambiphilic) dienophile, undergoing cycloaddition to both electron deficient and electron rich dienophiles. The cycloadducts of bromopyrone with dienophiles are isolable and are useful in the synthesis of diastereomerically pure cyclohexene carboxylates (Scheme 2).8... 

Wenkert et al developed an efficient new synthesis of trimethyl hemimellitate involving copyrolysis of dimethyl acetylenedicarboxylate with methyl a-pyrone-6 carboxylate. At the temperature required for addition the adduct as formed loset the lactone bridge as CO. ... 

Coumalic acid Cumalic acid EINECS 207-899-0 NSC 22978 2-Oxopyran-5-carboxylic acid 2-Pentenedioic acid, 4-(hydroxymethylene)-, delta-lactone a-Pyrone-5-carboxylic acid 2H-Pyran- arboxylic acid, 2-oxo-. Used in chemical synthesis. Crystals mp= 203-205 (dec) bpi20 = 218 Xm = 240, 290 nm (s =... 

The synthesis of the iron carbonyl adduct of cyclobutadiene carboxylic acid (212) has been reported.122 This synthesis involved photolysis of the pyrone (209c) in THF solution to yield the bicyclic lactone (213) in the presence of an excess of iron pentacarbonyl. The ester (212a) obtained from this process is light-sensitive, but hydrolysis yields a more stable acid (212b) in a maximum yield of 21%. 

Nalidixic acid 4.33) binds heavy metals between the carboxylic- and the oxo-groups (Crumplin, Midgley and Smith, 1980). It is not known if this plays a part in its biological action, which is inhibition of the synthesis of DNA (Section 4.0.5, p. 136). The antibacterial action of kojic acid (77./7), a pyrone extracted from certain fungi, is enhanced by metallic cations (Weinberg, 1957). Bacitracin, a polypeptide antibiotic (Section 13.2), loses its antibacterial action against Staph, aureus in the presence of EDTA the action is restored by bivalent cations (Adler and Snoke, 1962). 

ABSTRACT The review covers particularly the synthesis of fine chemicals via the formation of C-C bonds between carbon dioxide and hydrocarbons. In the reactions of CO2 with alkenes, dienes and alkynes a great number of carboxylic acids, dicarboxylic acids, esters, lactones and pyrones are formed, whether in stoichiometric or catalytic reactions. In each chapter the reactions are considered in the order of the transition metals applied. In addition, some syntheses will be mentioned which are closely related to transition metal catalysis, for instance the electrocarboxylation ofolefinic hydrocarbons. 

Nickel(O) complexes of alkjmes in the presence of carbon dioxide undergo oxidative cycli-zation to produce oxametallacycles 51 (Scheme 32).l l Direct cleavage of the oxametal-lacycle in the presence of strong acids affords unsaturated carboxylic acids 52 (Scheme 33). The coupling of di5mes with carbon dioxide leads to an efficient synthesis of bicy-clic a-pyrones such as 53 by a formal [2+2+2] cycloaddition (Scheme 33).l l... 

Although much less prevalent than the use of CO in lactone synthesis, direct incorporation of CO2 for the synthesis of lactones is advantageous due to lower toxicity while maintaining high atom efficiency. Louie and coworkers demonstrated that a formal [2 + 2 + 2] cycloaddition of bis-alkynes with CO2 yields pyrone derivatives under Ni(0) catalysis (Scheme 2.62) [117]. It is proposed that an initial cydometallation of one alkyne and CO2 yields a Ni(II) metallacycle, followed by insertion of the other alkyne and reductive elimination. Pd(0) has also demonstrated catalytic activity in carboxylations of methoxyallene [118] and 1,3-butadiene [119]. 

The major part of this review concerns chromones which possess a carboxyl or related group at C-2 but a few derivatives of the 3-carboxylic acids are known and discussed. Compounds in which the heterocyclic oxygen or the pyrone carbonyl oxygen is replaced by sulphur are also mentioned. The chemistry of chromones has been reviewed up to 1948 [1] and a survey (without references) of the synthesis of coumarins and chromones of therapeutic interest appeared in 1970 [2], Naturally-occurring chromones are covered in a chapter of a book by Dean [3]. The chromone-2- and -3-carboxylic acids have not been reviewed previously, although an early review of chromones [4] contains a short section on chromone carboxylic acids. 

Several methods are available for the preparation of chromone-2-carboxylic acid and its analogues. Those which lead to a carboxyl or an alkoxy- or aryloxy-carbonyl group at C-2 or C-3 are discussed in this section and those which lead to the formation of derivatives such as amides are described in the section on the chemical properties of the acids. Methods of synthesising chromone-2-carboxylic acids (or esters) may be divided into two main types (1) those in which the C-2 substituent is present at the cyclisation stage (the direct synthesis) and (2) those in which the substituent is formed from another group after the formation of the pyrone ring (the indirect synthesis). The former type is by far the most commonly used and is considered first. 

Related to this methodology is another one recently developed by Kirsch et al. [61], in which (Z)-aUylic alcohols are first converted into their trichloroacetimidates, and the latter are then subjected to a catalytic Sj 2 substitution of the trichloroace-timidate by a carboxylate group under the influence of complex 132, available in both enantiomeric forms (Scheme 2.26). If a p,y-unsaturated acid is used, an allyl P,y-unsaturated ester is obtained, which, after RCM and base-catalyzed migration of the double bond, affords a 5,6-dihydro-a-pyrone. The authors demonstrated the practical applicabihty of this methodology with the synthesis of (-)-rugulactone and other natural products. 

Pyrone synthesis by cycloaddition of CO2 to terminal alkynes (1-hexyne, 1-propyne) has also been investigated. This process can be catalytically promoted, albeit with low yield and selectivity, by Co [74] and Rh [75] complexes. Rh(dppe) (Ti -BPh4), in acetonitrile, at 390 K, catalyzed the formation of 4,6-dimethyl-2-pyrone from 1-propyne and CO2 (1 MPa) with a TON of 50 [75]. The Rh-catalyzed reaction has been proposed to proceed through a mechanism (Scheme 5.15) not involving an oxametallacycle intermediate species. The CO2 insertion into the Rh-C(sp )-o-bond of a Rh-alkenyl intermediate, obtained upon propyne dimerization, affords a linear unsaturated carboxylate which is converted into the pyrone. 

Both compounds are synthetically accessible through carboxylation of the corresponding anionic species. The propiolate obtained in the mono-carboxylation was not directly isolated, but esterified in situ with methyl tosylate. The radical scavenger 2,6-di-tert-butyl-p-cresol was added to minimize the risk of radiation-induced polymerization reactions. Literature reports of reactions on isolated carbon-14 labeled propiolates or acetylenedi-carboxylates are few, an exception being that of the catalytic hydrogenation of dimethyl [2,3- " C2]acetylenedicarboxylate , but the suitabUity and versatility of their unlabeled and carbon-13 labeled counterparts have been confirmed in numerous publications. Their reaction with a-pyrones, for example, could furnish doubly labeled aromatic systems with well defined substitution patterns, as demonstrated by the synthesis of methyl [ 1,3,a- C3]-salicylate (25), an intermediate in the preparation of [ CsJpindolol . 

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