Reactions lactones

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

Scheme 2.61. Syntnesis of (-)-panclicin D (2-258) and okinonellin B (2-261) employing the domino Mukaiyama aldol/lactonization reaction sequence.

The analogous reaction of alcohol derivatives 41 gave fused tetrahydrofurans and fused tetrahydropyrans 4250. As in the lactonization reaction the stereochemistry can be tuned... 

The zinc chloride-mediated tandem Mukaiyama aldol-lactonization reaction of aldehydes 21 and thiopyridylketene acetals 22 gave mainly the trans isomer 23. However, if the catalyst is stannic chloride and the reaction is carried out at -78 °C, then the cyclization is highly diastereoselective and yields the cis-isomer 24 <990L1197>. 

The bridged 1,4-dioxepanones 112 (R = TBMS X = H, Me) were prepared, unexpectedly, in moderate yield by radical deoxygenation of capuramycin derivatives. These products were rationalised in terms of a novel intramolecular radical glycosylation-lactonization reaction <00H(52)133>. 

Lactone ring opening can be both enzymatic and nonenzymatic, but it appears that the two mechanistic routes are seldom distinguished in metabolic studies [2], Thus, a number of the reports published on metabolism of lactones assume enzymatic hydration and do not examine what the relative contribution of nonenzymatic processes may be. Like for lactonization reactions, only very few in vitro biochemical studies address the question of relative enzymatic contribution and mechanism. 

In the intramolecular reactions studied by Bruice and Koshland and their co-workers, proximity effects (reduction in kinetic order and elimination of unfavourable ground state conformations) and orientation effects might give rate accelerations of 10 -10 . Hence, these effects can by themselves account for the enhancements seen in most intramolecular reactions. However, a factor of 10 -10 is less than the rate acceleration calculated for many enzyme reactions and certain intramolecular reactions, for example, hydrolysis of benzalde-hyde disalicyl acetal (3 X 10 ) (Anderson and Fife, 1973) and the lactonization reaction of[l] (10 ) where a trimethyl lock has been built into the system. If hydrolysis of tetramethylsuccinanilic acid (Higuchi et al., 1966) represents a steric compression effect (10 rate acceleration), then proximity, orientation, and steric compression... 

In an earlier study, interesting stereochemical aspects of this lactonization reaction were demonstrated, as illustrated in the synthesis of ( )-ambreinolide (equation 276)463... 

Applications of the lactonization reaction are illustrated in the syntheses of obtusilactones,530 benza-midopyranone,529 oxaspirolactone,527 diaxospirodione,528 and morphohinones526 (equations 294-298). 

Oxidation of glycol esters to ene-S-lactones. Reaction of glycal esters with m-chloroperbenzoic acid involves the expected epoxidation followed by cleavage of the oxide by the /n-chlorobenzoic acid formed. However, in the presence of BF3, the reaction produces a,/ -unsaturated 5-lactones, usually in excellent yield. This oxidation is also possible with pyridinium chlorochromate and BF3 as catalyst, but in lower yield.1... 

Methylene-y-lactones. Reaction of NaFp with a-bromopyruvate diethyl ketal results in the stable complex I, which on reaction with HPF is converted into the yellow crystalline, unstuhlc complex 2. The cation 2 serves an a-acrylic ester cation... 

An intramolecular lactonization reaction with extremely low catalyst loadings was reported in 1998 [77]. This development led to milder reaction conditions without concomitant loss of product yield. Thus, medium-sized lactones were accessible with a combination of as little as 0.03 mol% of FeCl2 and 0.03 mol% of a multidentate nitrogen-based ligand (Scheme 3.13). 

For unimolecular lactonization reactions, hydrolyses of aryl esters, Diels-Alder reactions, and porphyrin metalization reactions the validity of Eq. (18.2) has been demonstrated. 

Treatment of a-iodo lactone (45) with triethylborane under oxygen atmosphere gives the corresponding a-hydroxy lactone (46), via a-lactone radical species. This reaction comprises of SH2 reaction by Ef on the iodine atom of a-iodo lactones, reaction of the formed a-lactone radical with molecular oxygen, and subsequent hydrogen-atom abstraction from the solvent to form alkyl hydroperoxide (ROOH). Finally, by the addition of dimethyl sulfide for the reduction of the peroxide, the corresponding a-hydroxy lactone is obtained (eq. 2.24) [58]. 

Acetic acid can be used in carboxymethylation/lactonization reactions of arylalkenes 184 catalyzed by electrochemically generated Mn(OAc)3 and Cu(OAc)2... 

Fig. 51 Oxidative radical addition/lactonization reactions catalyzed by Mn(OAc)3...

Whereas a triplet 1,4-biradical has been assigned as the most probable intermediate at that time, later work on intramolecular trapping reaction favored the assumption of radical ion pairs [46]. Efficient lactonization reaction to form 51 during irradiation of pent-4-enoic acid 50 and 48 accounts for an olefin radical cation which undergoes electrophilic addition towards the carboxyl group. Another type of rearrangement has been detected in the photoreaction of tetramethylallene and 48 [47]. 5-Hydroxy-indan-2-ones 52 are formed in high yields probably via instable spiro-oxetanes 49b as intermediates. 

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