Y -Lactones formation

Homoenolate Reactivity The ability to generate homoenolates from enals and its application to the preparation of y-butyrolactones 30, through reaction with an aldehyde or aryl trifluoromethyl ketone, was reported independently by Glorius [8], and Bode and Burstein [9] (Scheme 12.4). A sterically demanding NHC catalyst is required to promote reactivity at the d terminus and to prevent competitive benzoin dimerisation. Nair and co-workers have reported a similar spiro-y-lactone formation reaction using cyclic 1,2-diones, including cyclohexane-1,2-dione and substituted isatin derivatives [10]. 

You and co-workers have demonstrated enantioselective y-lactone formations nsing glyoxalate 163, achieving up to 78% ee with the NHC derived from chiral triazohum salt 164, although with low levels of diastereoselectivity (Scheme 12.35) [70],... 

Scheme 8.7. y-Lactone formation initiated by an enzymatically liberated Nu (- C02 ). 

The photolysis of cyclic ketones, in general, results in homolytic cleavage of the carbon-carbon bond adjacent to the carbonyl function. For details of this process, the reader is referred to the review by Srinivasan.425 Included among the photoproducts are certain oxygen heterocycles, formed by cyclization of reactive intermediates. Thus, cleavage in a cyclic /3-diketone, such as tetramethylcyclobutane-1,3-dione or hexamethylcyclohexane-l,3,5-trione [Eq. (110)] is followed by cyclization on the oxygen atom to form a lactone.426,427 y-Lactone formation is also observed on photolysis of 2,2-diphenylindane-l,3-dione [Eq. (Ill)] in ether, and the process is reversible.428... 

Selective loop cleavage via intermediate y-lactone formation using methanesulfonic acid in MeOH liberates the N-terminus without concomitant cleavage of the peptide chain and allows determination of the sequence of the peptide without tagging strategies. 

In intramolecular cyclopropanation, Doyle s catalysts (159) show outstanding capabilities for enantiocontrol in the cyclization of allyl and homoallyl diazoesters to bicyclic y-and -lactones, respectively (equations 137 and 138) The data also reveal that intramolecular cyclopropanation of Z-alkenes is generally more enantioselective than that of -alkenes in bicyclic y-lactone formation . Both Rh(II)-MEPY enantiomers are available and, through their use, enantiomeric products are accessible. In a few selected cases, the Pfaltz catalyst 156 also results in high-level enantioselectivity in intramolecular cyclopropanation (equation 139) ". On the other hand, the Aratani catalyst is less effective than the Doyle catalyst (159) or Pfaltz catalyst (156) in asymmetric intramolecular cyclo-propanations In addition, the bis-oxazoline-derived copper catalyst 157b shows lower enantioselectivity in the intramolecular cyclopropanation of allyl diazomalonate (equation 140). ... 

Formation of lactones can occur though chemical cyclisation, although enzymatic formation is generally more frequent in nature. Glutamic acid is the presumed precursor for y-lactones formation during fermentation (Wurz et al. 1988). The mechanisms regulating the formation of lactones in wine are not known. 

There are numerous variations of cycloalkylating lactone formations. They may be classified into HGA ring closure of y-hydroxy acids or esters, 5n2 ring closure of y-bromoca xylates, lactonizations under participation of alkenic double bonds or y-lactone formation by carbenium rearrangements. 

Diazoacetates derived from simple primary alcohols also undergo y-lactone formation in moderate to good yield. Through the use of Rh2(4S-MPPIM)4 as catalyst, Eq. (42), excellent stereocontrol is attainable (up to 96% ee) [60,61]. 

With the foregoing information, partial structures of the necic acid corresponding to sceleranecic dilactone and of the C8H12O4 oxidation product may be written as CXCVIII and CXCIX, respectively. Structure CXCVIII satisfies the 8- and y -lactone formation, especially the... 

Ali and Alper later developed a method for y-lactone formation under neutral conditions from allylic alcohols according to Scheme 23, involving Pd(0) and dppb. The same protocol was also applied to synthesis of a,/3-butenolides from propargylic alcohols. Other bidentate or monodentate ligands give inferior results, and this correlates well with bite angle effects on the rate of the CO insertion reaction. Also, the allylic alcohol needs to be a-alkyl substituted to facilitate ring closure, in accordance with other studies.t t This process was postulated by the authors to be of the carbopalladative type. 

A facile y-lactone formation is realized by the carbonylation of 5-hydroxy-2-aIkynyl methyl carbonates at room temperature (r.t.) under 1-10 atm of CO (Scheme The primary products of the carbonylation are a-vinylidene-y-lactones, but partial or complete isomerization of the a-vinylidene group to the conjugated 1,3-diene takes place depending on the reaction conditions. 

PolyaFS seems to decompose by HF elimination and this mode of decomposition may also be expected to operate in the copolymers with high aFS contents. However, the infrared spectrum of a deconq)Osed copolymer (Figure 12) contained a strong carbonyl absorption at 1765 cm (y-lactone) that was not present in the spectrum of the original copolymer. In addition, the appearance of a new carbonyl carbon resonance at 6q=177.2 ppm and the appearance of a new resonance at 6 =85.4 ppm in the C-NMR spectra of aged copolymers suggest that the degradation process involves y-lactone formation. 

Murakami, M. Tsuruta, T Ito, Y. Lactone Formation by Rhodium-Catalyzed C-C Bond Cleavage of Cyclobutanone. Angew. Chem., bit Ed. 2000,39,2484-2486. 

Need to Introduce tosylate early for timing reasons (avoid y-lactone formation from Incipient 5-lactone). 

In synthesis of isotetronic acid derivatives, aldol-type reactions of 1,2-dicarbonyl substrates including oxalyl chloride and pyruvates are used as powerful mefhodologies. For instance, Langer et al. reported systematic investigations on such reaction of oxalyl chloride 21 wifh l,3-bis(trimethylsilyloxy)-l,3-butadienes 22 or 24 as masked dianion equivalenfs (Scheme 10) [21]. By using a catalytic amoxmt of MesSiOTf, y-lactone formation smoothly occurred to yield the lactones (E)-23 or (Z)-25, respectively. This methodology is also effective for the synthesis of medium-sized bicyclic y-bufenolides such as 25c [22]. 

Gravel et al. [71] reported an interesting methodology for y-lactone formation through ring-expanding reaction of oxetane-2-carbaldehyde 103 (Scheme 46). N-Heterocyclic carbene derived from an imidazolinium salt 105 was found as the most potent catalyst for this reaction. This reaction is also applicable for the synthesis of 8-pentanolides. 

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