Diels 8-lactone preparation

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

The Baeyer-Villiger reaction has found considerable application in the synthesis of prostaglandins. One common pattern involves the use of bicyclo[2.2.1]heptan-2-one derivatives, which are generally obtained by Diels-Alder reactions. For example, compound 10 is known as the Corey lactone and has played a prominent role in the synthesis of prostaglandins.237 This compound was originally prepared by a Baeyer-Villiger oxidation of 7-(methoxymethyl)bicyclo[2.2.1]hept-5-en-2-one.238... 

The pyranocoumarin 105 can be prepared via a three-component Diels-Alder reaction between 4-hydroxycoumarin, ethyl vinyl ether and an a-dicarbonyl compound. Similarly to the above, upon treatment of 105 with sulfuric acid in THF, hydrolysis and rearrangement occur to give the furofurochromenone 106. The hemiacetal functionality in 106 may then be oxidized with pyridinium chlorochromate (PCC) to give the lactone 107 <2001EJ03711> (Scheme 28). 

The key reaction in Jung et al. s proposed assembly of Plaunol B (81a) and C (81b) was an intermolecular Diels-Alder reaction between a diene and an allenic lactone that should give the exo-methylene group in the natural product (Scheme 19.16) [20], The phenyl-substituted lactone 83 was prepared as a model for the eventual furan lactone of the plaunols. Cydoaddition of 82 possessing a TBS enol ether and... 

Miki and Hachiken reported a total synthesis of murrayaquinone A (107) using 4-benzyl-l-ferf-butyldimethylsiloxy-4fT-furo[3,4-f>]indole (854) as an indolo-2,3-quinodimethane equivalent for the Diels-Alder reaction with methyl acrylate (624). 4-Benzyl-3,4-dihydro-lfT-furo[3,4-f>]indol-l-one (853), the precursor for the 4H-furo[3,4-f>]indole (854), was prepared in five steps and 30% overall yield starting from dimethyl indole-2,3-dicarboxylate (851). Alkaline hydrolysis of 851 followed by N-benzylation of the dicarboxylic acid with benzyl bromide and sodium hydride in DMF, and treatment of the corresponding l-benzylindole-2,3-dicarboxylic acid with trifluoroacetic anhydride (TFAA) gave the anhydride 852. Reduction of 852 with sodium borohydride, followed by lactonization of the intermediate 2-hydroxy-methylindole-3-carboxylic acid with l-methyl-2-chloropyridinium iodide, led to the lactone 853. The lactone 853 was transformed to 4-benzyl-l-ferf-butyldimethylsiloxy-4H-furo[3,4- 7]indole 854 by a base-induced silylation. Without isolation, the... 

Diels-Alder reactions with furans constitute a major class of cycloaddition reactions, which have been used for the preparation of a variety of new compounds. Some examples will be given in this section. A one-pot stereoselective synthesis of tricyclic -y-lactones was achieved via Diels-Alder reactions of 2-methoxyfuran with masked o-benzoquinones, which are in turn available from the corresponding 2-methoxyphenols <99CC713>. 

Encouraged by this calculation, the racemic ester 46 was prepared readily in 5 steps from a-ionone in 65% overall yield via a known sequence used in the synthesis of forskolin [Scheme 9].14 The subsequent intramolecular Diels-Alder reaction of 13 in refluxing n-decane gave the tricyclic lactone 47 in 65% yield.52... 

It is noteworthy that stereochemical control of the two new stereogenic centers at C4a and Cl2b ultimately stems from the stereochemistry at Cl through the intramolecular Diels-Alder reaction. Hence, an optically pure 46 should lead to an enantioselective preparation of a-epoxy lactone 48, thereby ultimately leading to an enantioselective synthesis of arisugacin A [1], LAH reduction of ( )-a-epoxy lactone 48 led to epoxy diol 49 in 78%... 

Compounds in this class are usually made from specific precursors with the ultimate functionalities appearing in the starting materials. Syntheses in which one new bond is formed (cyclizations) usually involve substitution or condensation reactions. Two new closures with potentially some generality have been noted in this chapter. One of the intramolecular Diels-Alder reactions (see Section 13.12.8.1) and the other RCM (see Section 13.12.8.1). The Baeyer-Villiger reaction is still very much used for the preparation of lactones. A supported catalyst and a recyclable catalyst carried in an ionic liquid have been introduced for use in Baeyer-Villiger oxidations from other areas. 

Trani-fused bicyclic y-lactones (7) have been conveniently prepared, in a one-pot process, from conjugated nitroalkenes, by way of the expected transesterihcation-intramolecular hetero Diels-Alder (HAD) reaction, followed by the transformation of a functional group using ( )-l-ethoxy-2-nitroethylene (5) and prim-, sec-, and tert-y,e-unsaturated alcohols (6) having two methyl substituents at the terminal position as illustrated in Figure 2.2 (Wada and Yoshinaga, 2003). 

In contrast, the intermediately formed methylenecyclopropane 44 reacts with electron-rich alkenes to give cycloadducts, e.g. 45, with the bis(acceptor)methylenecyclopropane reacting as a heterodiene. This hetero-Diels-Alder reaction is also applicable to electron-rich alkynes, e.g. formation of 46. Thus, a solution of 3-acetoxy-5,5-dimethyl-2-(l-piperidinocyclo-propyl)cyclohexen-2-enone (47) and 1 equivalent of alkyne was reacted at 36°C for 4 hours. Alkyl-substituted alkynes, although applied in great excess, did not form any products. Depending on the substituents, further acidic hydrolysis opens up a method for the preparation of acetates or lactones. 

Vandewalle et al. have also used oxidative ring opening of one side of a norbomanone to prepare a number of iridoids, culminating in a synthesis and correction of the structure of specionin. At first they described the synthesis of teucrium lactone (425) and a loganin precursor (472) from the Diels-Alder adduct 473 of cyclopentadiene and methyl ( )-crotonate (Scheme 44). The same paper describes the preparation of the all-enafo-isomer 474 of ketone 475, from... 

Fukuyama and co-workers constructed the [2.2.2]azabicyclohexane framework enantioselectively via the asymmetric Diels-Alder reaction and MacMillan s catalyst ent-5a and obtained a lactone without purification. Subsequent transformation led to the preparation of (—)-oseltamivir in 22% yield from benzyl chloroformate (Scheme 10.3) [37]. 

The use of the 4tt diene participation of vinylnitroso compounds in Diels-Alder reactions in the preparation of aryl pyruvate oximes,76a c e 8>h amino acids,76a,c 8 y-hydroxynitriles,76ad 8 y-lactones,76dg pyridine N-ox-ides,76f and pyrroles77 is summarized in Scheme 9-III. The intramolecular Diels-Alder reactions of in situ generated and unactivated vinylnitroso compounds have been shown to proceed readily employing electron-rich olefins, and the course of the reaction has been shown to proceed preferentially through an endo transition state [Eq. (36)].79... 

Ducrot <99SL240> used the four carbons of furan to build a cyclohexyl unit by oxidation of 263 followed by a direct aldol cyclization to give 264. Casiraghi <00JOC6307> prepared the lactone portion of 265 from a silyloxy furan aldol reaction followed by another aldol process to produce 266 as a precursor to various carbasugars, Miyashita used furan in a non-traditional way in a Diels-Alder approach to zoanthamine <02TL1705>. The pendant furan of 267 was oxidatively opened to produce a dienophile, ultimately leading to tricycle 269. 

The enantiomers of 2-cyclohexy(-2-hydroxy acetic add 12 and their esters are conveniently obtained from the corresponding mandelic adds (or derivatives) by catalytic hydrogenation with a platinum catalyst16 17. The methyl ester has been used for the enantioselectivc protonation of lactone enolates (Section D.2.1.) and the chiral diene prepared analogously to the O-methylmandclic acid derivatives11-13 described in the preceding section in diastereoselective Diels-Alder reactions (Section D. 1.6.1.1.1.). 

Biphilic Reactions with Dienes and with Unsaturated Carbonyl Compounds. The Diels-Alder reactions of the aj8-unsaturated lactone (40) have been described. The lactone is prepared by treatment of chloro-methyldichlorophosphine (41) with propiolic acid and then hot acetic... 

The use of an acetal to tether the diene and dienophile has been investigated by Craig and co-workers [15], Preparation of the unsymmetrical acetal precursor was best achieved via the corresponding enol ether. For example, the isopropylidene-linked triene 28 was synthesized in two steps from acetate 29. Tebbe methylenation of 29 afforded enol ether 30, which was used directly in a Pd -catalyzed addition of the dienophile 3 to form 28 (acid-catalyzed addition with pTSA proved inferior). Thermolysis of 28 in toluene at 165°C allowed a remarkably facile and completely regiospecific cyclization to take place. Acidic methanolysis of the Diels-Alder adducts resulted in cleavage of the tether and isolation of a 2.7 1 mixture of lactones 31 and 32 in 72% yield (Scheme 10-9). 

The pyrazino[2,l-i][l,3]oxazinium trifluoroacetate (319) is formed in good yield from the pro-tonated pyrazine derivative (318) by intramolecular cycloamination, together with a small amount of the expected Diels-Alder product (Equation (87)) <89T6519>. Saturated pyrazino[2,l-c][l,4]oxazinones (320) and (239) were prepared by lactone formation, in good yields (Equation (88)) <75IJC468, 78MI 825-01 >. 

A variety of other auxiliaries have been developed that gave excellent asymmetric induction in the Diels-Alder reaction. Helmchen and Schmierer also developed an auxiliary based on camphor that is quite useful.234 In addition, Helmchen prepared the lactone auxiliary 281 and the imide auxiliary 283 and showed they give opposite enantioface selectivity in the Diels-Alder reaction.235 in the presence of a Lewis acid such as TiCU, differences in coordination site led to a different chiral face in the transition state of the... 

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