Corey lactone, synthesis

The Baeyer-Villiger oxidation is a synthetically very useful reaction it is for example often used in the synthesis of natural products. The Corey lactone 11 is a key intermediate in the total synthesis of the physiologically active prostaglandins. It can be prepared from the lactone 10, which in turn is obtained from the bicyclic ketone 9 by reaction with m-chloroperbenzoic acid (MCPBA) " ... 

The catalyst played an important role in the asymmetric synthesis of Corey lactone based on high diastereofacial selective Diels-Alder reaction between chiral acrylate 37 and 5-benzyloxymethylcyclopentadiene [41] (Equation 3.9). The cycloadduct 38 was then converted into chiral Corey lactone [42] by a three-step procedure. 

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... 

Amputch MA, Little RD (1991) Tetrahedron 47 383. Utley JHP, (1987) Electrogenerated bases. In Steckhan E (ed) Topics in current chemistry. Springer, Berlin Heidelberg New York, p 133 Little RD, Sowell CG (1991) Stereoselection in electroreductive cyclization. Construction of a Corey lactone precurser. In Little RD, Weinberg NL (eds) Electroorganic synthesis, festschrift for Manuel M. Baizer. Dekker, New York, p 323 Shono T, Mitani M (1971) J. Am. Chem. Soc. 93 5284... 

The synthesis of AFP-07 is shown in Scheme 9 [107], The enone 59 prepared from the Corey lactone was reduced with aluminum reagent and protected with f-butyidimethylsilyl chloride. Fluorination of the lactone 60 under the standard conditions gave the difluorolactone 61. The carbonyl group of the difluorolactone... 

This stereochemical control in hex-5-enyl radical cyclizations can be used for the synthesis of highly functionalized cyclopentanes with vicinal trans- or cis-dialkyl-substituents. The synthesis of a versatile prostaglandin intermediate, Corey lactone 12, from the intermediate 6a (Y = OMe) has been described [14]. 

Stereoselective intermolecular photoadditions of alkenes to enones have been elegantly utilized in the synthesis of naturally occurring compounds or compounds of special interest. Sato and collaborators100 have applied the photoaddition of dioxinone 208 to the chiral r/.v-diol 207 for a one-pot synthesis of the Corey lactone 210, which possesses considerable utility in the preparation of prostaglandin derivatives (Scheme 45). 

Although the earliest syntheses of the Corey lactone, using a cyclopentadienyl-thallium species, were not very attractive, it was soon found that the lactone could be usefully generated by a Baeyer-Villiger reaction on a bicycloheptenone.8 In turn, this derives from an easy [2 + 2] cycloaddition reaction between dichloroketene and cyclopentadiene (Scheme 30.2).9 Additionally, an intermediate of the lactone could be resolved by way of the a-methylbenzylamine salt of its opened hydroxyacid, bringing the resolution step earlier in the synthesis than previously.10... 

The synthesis of latanoprost (1) commences with the lactone 5 derived from the Corey lactone (Scheme I).11 12 The early introduction of the p-phenylbenzoyl protecting group12 in this lactone affords crystalline intermediates in the synthesis that are easy to handle and purify. In the next step, the primary alcohol functionality in the lactone 5 was oxidized using Pfitzner-Moffat conditions (DCC, DMSO and phosphoric acid) to yield the aldehyde 6. The crude aldehyde was then treated with dimethyl (2-oxo-4-phenyl)-phosphonate under Wadsworth-Emmons conditions (NaH, DME) to afford the enone 7 as a white crystalline solid in 59% yield. 

A stable tetrahedral intermediate is more likely in the reduction of lactones, and DIBAL is most reliable in the reduction of lactones to lactols (cyclic hemiacetals), as in E.J. Corey s synthesis of the prostaglandins. The key step, the hydride transfer from Al, is shown in the green frame. 

A PGE related compound, lubiprostone (23) displays a quite different spectrum of activity. This compound has been recently approved for treatment of chronic constipation and is being investigated for its effect on constipation-predominant irritable bowel syndrome. It has been ascertained that the drug interacts with specific ion channels in the G1 tract causing increased fluid output into the lumen. Starting material for the synthesis (13) comprises yet another variant on the Corey lactone. Condensation... 

One of the earliest examples of the synthetic promise of radical reactions for preparing polycyclic products was provided by Corey s y-lactone synthesis. This approach was actually based on a well-known reaction of a-carbonyl radicals, generated by manganese(iii) oxidation of carboxylic acids, with unsaturated substrates. The mechanism of the basic steps shown for the preparation of lactone 418 (Scheme 2.140) involves initial addition of the a-carbonyl radical 419 to the double bond of styrene, followed by oxidation of the radical intermediate 419a to carbocation 419b, and subsequent intramolecular reaction with the carboxyl nucleophile to yield the lactone product. 

An application of these diazaaluminolidine catalysts to the synthesis of prostaglandins is shown in Sch. 33 [57]. The Corey lactone 275 is a key intermediate in an elegant route to prostaglandins in its original form 275 was prepared from the racemic bicycloheptanone 274 and obtained optically active by intermediate resolution [58]. A direct preparation of optically pure ketone 274 was achieved by cycloaddition of the substituted cyclopentadiene 272 and dienophile 261 with catalyst 266, which gave the adduct 273 in 95 % ee and 94 % yield. 

A by now classic retrosynthesis of prostaglandins PGFj and PGEj (Fig, 4) leads to the bicydic lactone [12), five-carbon phosphonium salt [13], and phosphonate [14] (19). These compounds contain all the carbon atoms of the prostaglandins and, in [12], aU but one of the chiral centers. Lactone [12] has come to be knovm genetically as the Corey lactone, and its synthesis in one enantiomeric form has been the subject of numerous complementary investigations. 

An extremely efficient synthesis of lactone [41] is provided (33,34) by asymmetric synthesis (Fig. 10). Alkylation of the anion of cyclopentadiene with methyl bromoacetate gave the unstable diene [59], Immediate asymmetric hydroboiation with (+)-di-3-pinanylborane gave, after oxidative workup, the hydroxy ester [60] in about 95% e.e. Lactonization involved conversion to mesylate [61] and saponification. The crystalline lactone [41] was readily brought to an enantiomerically pure state. This route is apparently the basis for commercial quantities of compound [41], the Corey lactone, and other prostaglandin intermediates offered by the Hungarian firm Chinoin. 

Figure 9 Ferrier synthesis of a Corey lactone equivalent.

In a study by Wicha directed to the synthesis of prostaglandins from the Corey lactone, the use of BFs-EtaO to catalyze the addition of the lithium sulfone anion (470) to aldehydes was demonstrated (equation 109). The use of Lewis acid catalysis results in significantly improved yields for the addition component of the Julia coupling. In this example, the addition of either the lithium or the magnesium sulfone anion proceeded in low yield. With the addition of BF3-Et20, the p-hydroxy sulfone can either be isolated, or directly converted to an alkene in one pot. This sequence was originally developed to deal with the specific problem of a-hydroxy aldehydes, and the difficulty of sulfone anion addition to these adducts. Other problems with addition of the sulfone adduct may be amenable to this solution as well. 

A superb example of the synthetic utility of the iodolactonization reaction in organic synthesis is the conversion of the bicyclo[2.2.1]heptenone below into the Corey lactone. The latter compound possesses four contiguous stereogenic centers and is an important precursor for the synthesis of prostaglandins. 

The stereoselective five-ring annulation is the cornerstone in a synthesis of Corey s lactone, starting from readily available 3-deoxy-1.2 5,6-di-0-isopropylidene-a-D- v7)o-hexofuranose (8)54. Treatment of the intermediate 5-hexenol with thiocarbonylbis(iniidazole) followed by reaction with tributyltin hydride (Barton deoxygenation) gives exclusively the bicyclic compound 9 with the /i-orientated methoxymcthvl substituent. The cyelization product has the correct absolute configuration for the Corey lactone, to which it can be converted in four additional steps. 

---