Lactones, preparation

Ring opening of a 4-(hydroxyalkyl)-substituted oxazolone using dimethylamine gives an amide 245 that can be used as an intermediate in a subsequent intramolecular cyclization to prepare lactones 247 (Scheme 1.19) ... 

Macrolides. Steliou, Hanessian, and co-workers- have prepared lactones and lactams in moderate to excellent yield by treatment of ro-hydroxy or ru-amino carboxylic acids with catalytic amounts of di-r -butyltin oxide in refluxing mesitylcne or xylene in a Dean-Stark apparatus for 12 24 hours. The method has the advantage of high dilution, since the tin reagent is regenerated continuously. As expected, yields arc low for medium-sized rings. 

Intramolecular condensation of co-hydroxycarboxylic acids is a standard method to prepare lactones. Acid catalysts or more elaborate mediators are usually required as well as continuous removal of water. Transition-metal-catalyzed cyclocarbonylation of unsaturated alcohols is a fascinating alternative, which proceeds under neutral conditions [26]. Intramolecular hydroesterification of... 

The (S)-(+)-y-butyrolactone-Y-carboxylic acid is a useful Intermediate for the synthesis of pheromones,4 natural lignans,5 and other derivatives.6 In the same manner, but starting with D-glutamic acid, the (R)-(-)-lactone acid may be prepared. Lactonization occurs with full retention of configuration at the chiral center.8 9 Recently, authors have described an efficient method which allows the formation of derivatives of the (R)-(-)-lactone from the more available (S)-(+) counterpart.10... 

Sato [3] and Koyama [4] prepared lactone copolymers, (V) and (VI), respectively, that were effective in positive resist compositions suitable for use in super-microlithography processes such as the manufacture of super-LSI and high-capacity microchips. 

An example of the utilization of a bridged bicyclic ketone for preparation of an acyclic moiety is the stereoselective synthesis of the C-21 to C-27 segment of rifamycin-S, a member of the ansamycin family of antibiotics (Scheme 18). Rao et alP used ketone (61), derived from furan, to prepare lactone (62). Exhaustive reduction of (62) provided the segment (63), which contains five chiral centers of lifamycin-S. 

Many of the methods listed for the preparation of hydroxy acids (Table 47) have been used to prepare lactones directly. Reduction of levulinic acid, CHjCOCHjCHjCOjH, by sodium and alcohol or by catalytic hydrogenation over Raney nickel leads to "y-valerolactone. S-Captolactone is prepared in a similar manner from y-acetobutytic acid. Other S-lactones have been formed by catalytic hydrogenation of the corresponding aldehydo... 

The same group further extended this chemistry to prepare lactones 40 and 41, and also used a modified approach towards other diacylglycerol (DAG) analogues 44 and 45. This latter approach involved synthesis of the spirocyclic lactone intermediate 43 by addition of a Grignard maganesium alkoxide to 42 and the PCC oxidation (Scheme 7). ... 

Skrydstrup and cowoikers [131] used substrate I-type 182 in their formal total synthesis of PKC inhibitor balanol to prepare lactone 183 this was, however, accompanied by a certain amount of 8- do-cyclization product 184 (Scheme 6.52). 

Fischer made extensive use of the reactions of the sugars with phenylhydrazine, a reagent which he had discovered in 1875. Fischer also oxidised the sugars to mono- and dicarboxylic acids, reduced the carbonyl function to a hydroxyl group, and prepared lactones (cyclic esters) from the monocarboxylic acids. Fischer also used a reaction devised by Heinrich Kiliani (1855-1945) in which the carbon chain of a sugar could be extended. Thus a five-carbon sugar could be converted to two six-carbon sugars because a new asymmetric centre had been added. 

A number of reports have appeared which deal specifically with the creation of the AB portion of the trichothecene skeleton. The majority of this work, as shown in Scheme 7, concerns itself with alternative Diels-Alder strategies for the construction of the A ring. When methyl coumalate (120) is used as the dienophile the AB system results immediately, although a number of manipulations are needed to convert the Diels-Alder adducts to useful synthetic intermediates. In this fashion Tatsuno and Nakahara (707) have intercepted a previous intermediate (121) in their 12,13-epoxytrichothec-9-ene (1) synthesis (see Scheme 5), while Kraus and Frazier (97) have prepared ketone (122), an olefin isomer of the calonectrin intermediate (115) (see Scheme 6). Most recently, Banks and co-workers (72) have prepared lactone (124) from the Diels-Alder adduct (123). Scheme 8 summarizes some early work from Goldsmith s laboratory (57) in which the cis fusion of the AB system was generated from a cuprate addition to enone (125). 

Finally, two relatively long syntheses to verrucarinolactone derivatives exist. The first by Koga and co-workers (140) accounts for the synthesis of chiral material as their sequence originates with L-glutamic acid (271). Trost and McDougal (144) have prepared lactone (275) via a bond cleavage reaction (273 274) developed in Trust s laboratories. 

In 2013, Shi and coworkers described the first example of phenolic hydroxy group-directed C-H carbonylation to prepare lactones (Scheme 3.25) [50]. Using 5mol% Pd(OAc)2, 10mol% Cu(OAc)2, 2equiv. of Na2C03, and O.Sequiv. of PivOH, dibenzopyranones could be synthesized from 2-arylphenols under an atmospheric pressure of CO and air. The reaction is of wide substrate scope, whereas the steric hindrance and electronic character of phenolic aromatic ring are critical to the yield. 

Scheme 3.25 Pd-catalyzed C-H carbonylation of phenol to prepare lactones.

For this problem, it is best to first work in the retrosynthetic direction. Cyclic ethers such as 1 can be generated from 2 via the WrUiamson ether synthesis. The substrate for this reaction can arise from a diol, such as 3, which in turn can come from reduction of a cychc ester such as 4. Finally, we know that we can prepare lactone 4 Ifom ketone 5 using the Baeyer-VrUiger reaction. 

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