4-Pyrone 2- -, ring synthesis

Pyrones, benzo[a]fluorenones s. 16, 821 4-Pyrone ring synthesis and degradation... 

Pyrone ring synthesis and degradation Double ring closure to condensed 4-pyrones... 

The Pechmaim reaction has found extensive appHcations for the synthesis of numerous coumarin derivatives (39). Coumarin derivatives substituted in the pyrone ring can be obtained by condensing phenol with beta-ketoesters. For example, 4-methylcoumarin (3) is obtained with ethyl acetoacetate... 

The Baccatin III synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.54. Diels-Alder reactions are prominent in forming the early intermediates. In Step A the pyrone ring served as the diene. This reaction was facilitated by phenyl-boronic acid, which brings the diene and dienophile together as a boronate, permitting an intramolecular reaction. 

These investigations shed considerable light on the synthesis of the Y-pyrone ring however, it is unlikely that any conclusions regarding the biosynthetic process could be drawn from them. 

Trost used a rhodium(i)-catalyzed hydroboration to obtain a key intermediate 139 in 90% yield in the synthesis of the pyrone ring of the natural product (—)-malyngolide 140 (Scheme 17).143... 

Another enantioselective synthesis of longifolene, shown in Scheme 13.27, uses an intramolecular Diels-Alder reaction as a key step. The alcohol intermediate is resolved in sequence B by formation and separation of a menthyl carbonate. After oxidation, the pyrone ring is introduced by y addition of the ester enolate of methyl 3-methylbutenoate. 

The pyrone ring then acts as the dienophile in the intramolecular Diels-Alder cycloaddition, which was conducted in a microwave oven. The final step of this synthesis is a high-temperature ester pyrolysis to introduce the exocyclic double bond of longifolene. 

Another synthesis of pterocarpans starts from the coumestan system. LAH treatment results in reductive cleavage of the a-pyrone ring (Scheme 52). Benzofuran derivative (242) is thermally cyclized to (243) (64JCS4212 see also 78IJC(B)372), which may also be formed... 

The increased development of transition metal-catalyzed cross-coupling methods to form C-C bonds has served as an impetus to find methods to synthesize 3-halochromones and 3-haloflavones. The synthesis of 3-halochromones and flavones can be achieved with the addition of halogens across the double bond of the pyrone ring by reaction with a halogenating reagent (e.g., Br2) followed by spontaneous, or base-induced, elimination (Scheme 48). Synthesis of these important compounds has been recently reviewed <2003RCR489>. 

A simple two-step synthesis of the a-pyrone ring system209 has been applied to the synthesis of bufadienolides.210 Reaction of the known a/3-unsaturated aldehyde (416) with the dimethyl acetal of chloroketen [ClCH=C(OMe)2] gave a 57% yield of the intermediate 2,2-dimethoxy-3 -chloro-3,4-dihydropyran (417) which on reaction with sodium methoxide in DMSO afforded the a-pyrone (418) directly in 64% yield. 

Lown and Sondhi were interested in the synthesis of chromophores of the anthracycline antibiotics in which the quinone ring c was replaced by a y-pyrone. The y-pyrone ring was prepared by an oxidative cyclization mediated by DDQ, presumably proceeding via the quinone (Scheme 27). 

Money, Scott and coworicers utilized a similar strategy of protecting the labile polyketcxie as a pyrone ring. As shown in equation (150), pyranopyrone (133) reacts with aqueous base to give orsellinic acid, presumably by way of the intermediate triketo diacid (134). 4 procedure was found to be quite general equation (151) shows a further application in the synthesis of pinosylvin, (135). ... 

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. 

Various types of commercially available chiral precursors, generally members of the chiral pool, have been used for the stereoselective synthesis of chiral 5,6-dihydropyran-2-ones [6] (i) carbohydrates, mainly monosaccharides 7, 19, 30] (ii) chiral hydroxy acids [8, 20, 31] (iii) chiral epoxides [9, 21, 32] and (iv) other various types of chitons, including those prepared with the aid of microorganisms or enzymes [10, 22, 33]. As discussed above, there are cases in which one or two of the stereogenic carbons of the chiral precursor are transmitted intact to C-5/C-6 of the pyrone ring of the target molecule. In other cases, however, these carbons are not transferred as such and may even disappear, but only after they have influenced the formation of other stereocenters via internal induction. 

---