Corey’s lactone

Treatment of bicyclic lactones 66, derived from Diels-Alder reaction of 3-carboxy-2-pyrone under standard radical conditions using (TMSlsSiH, leads to bridged lactones 67, which can smoothly be converted to bicyclo[3.3.0]-lactones 68 (Scheme 10). For X = CHaOMe, this cascade of rearrangements took place in a 78% overall yield, providing 68 in diastereomerically pure form. Three additional steps provided a novel route toward Corey s lactone 69. 

Allylic alcohols from sulfones.1 Polish chemists have extended the Julia synthesis of alkenes (11, 474) to a synthesis of allylic alcohols. In the presence of 1 equiv. of BF3 etherate, a-alkoxy aldehydes react with lithiafed sulfones to form adducts that are converted to allylic alcohols on reduction with sodium amalgam. This reaction was developed specifically for a synthesis of prostaglandins from Corey s lactone-aldehyde, but should have wider application. 

An example of an all-carbon inverse electron demand Diels Alder reaction is given in the short synthesis of Corey s lactone 69 that was reported recently by Marko et al. ... 

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. 

OTHP 0SiMe2f-Bu Fluoro Corey s lactone 1 -Fluoro-1 -methylcarbapenem... 

Although Cu(i) catalysed conjugate addition was known as early as 1941 and the first report of a lower order (L.O.) cuprate appeared in 1952/ ° the commonplace use of such reagents did not occur until after seminal publications around 1966/ Starting around 1975, the prostaglandins and their analogues became the first major application of Cu(i)-mediated 1,4-addition reported by the pharmaceutical industry use of Corey s lactone aldehyde, itself the product of a 10 step synthesis, was circumvented, and late-stage diversification of both the a and p side chains became possible. 

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. 

Corey s double activation procedure (Method 2) does not use an external reagent to activate the functional group, but effects cyclization by heating a solution of the 2-pyridinethiol ester of a hydroxy acid for a prolonged period. Several pieces of evidence point to the intermediacy of 2 in this lactonization.10 If one accepts this intermediate, it follows that a hydroxy(2-pyridinethiolJ ester, heavily substituted near the reaction centers (i.e., near the hydroxyl and acyl groups), would encounter a high... 

Method 2. Corey s double activation method for lactone formation is patterned after Mukaiyama s procedure for peptide formation and involves refluxing a solution of the 2-pyridinethiol ester of a hydroxy acid in a high-boiling solvent for a prolonged period of time.6... 

A recent display of such potential may be se i in Corey s excellent synthesis of ( )-Ginkgolide Oxidation of the lithio enolate of lactone (145) provided the alcoholic derivative in, presumably, good yield and with a high degree of stereocontrol. 

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. 

Halolactonizations have been used extensively for achieving high degrees of functionalization in a regio- and stereo-controlled manner. The conversion of (284) into (285 equation 101) is a key step in Corey s prostaglandin synthesis to prepare the central intermediate (286). For p,7-unsaturated acids like (287) the P-lactone (288) is formed under kinetic control, which then equilibrates to the 7-lactone isomer (2 9 equation 102). ... 

One of the key Intermediates in Corey s total synthesis of prostaglandins is the lactone (35) whose optically active form was obtained by resolution of (+) 36. Upon analysis of the sequence of reactions from cy-clopentadiene to 35 one would readily visualize the possibility of carrying out microbial resolution of various Intermediates along the synthetic pathway. One such resolution has been accomplished by microbial reduction of the (+) ketone 37 with Saccharomyces drosophylarum to yield the (+) exo and (-) endo alcohols (38 and 39). These were separated by chromatography and were oxidized to the optically active ketones (37).63 One of these was converted to 36. 4... 

Accordingly, ( )-alcohol A was oxidized to give B. Asymmetric reduction of B with Corey s CBS reagent gave (5)-A (79% ee). The 5-configuration of A was confirmed by its conversion to the known lactone (5)-C. Then, the ester (5)-D prepared from (5)-A was subjected to the Claisen rearrangement to... 

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