Lactones five-membered

Hydrofuranones, synthesis from furans and application in organic synthesis 83MI5. 

Transition metal-catalized reactions of alkynes in the synthesis of fu-ranones and furandiones 88CRV1081. 

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The isocoumarin 151 is prepared by the intramolecular reaction of 2-(2-propenyDbenzoic acid (149) with one equivalent of PdCbjMeCN) . However, the (Z)-phthalide 150 is obtained from the same acid with a catalytic amount of PdjOAc) under 1 atm of Oi in DMSO, alone is remarkably efficient in reoxidizing Pd(0) in DMSO. The isocoumarin 151 is obtained by the reaction of 2-(l-propenyl)benzoic acid (152) under the same conditions[4], 2-Vinylbenzoic acid (153) is also converted into the isocoumarin 154, but not to the five-membered lactone) 167,170],... 

The cyclization of o-halogenobenzoic acids with copper acetylides mainly leads to the formation of five-membered lactones (66JOC4071 69JA6464) (Scheme 115). Only in the case of the reaction of o-iodobenzoic with CuC=C—n-C3H7 does the formation of a mixture of y- and 5-lactones occur (Scheme 116). 

The interaction between a 4-iodopyrazole-3-carboxylic acid and copper ace-tylides having both donor and acceptor substituents at the triple bond generated six- rather than five-membered lactones, as in the aromatic series (Scheme 117). 

The attack of bromine or iodine on ,y-unsaturated acids (29) usually gives five-membered lactones (30)... 

Intramolecular insertion reactions show a strong preference for formation of five-membered rings.219 This was seen in a series of a-diazomethyl ketones of increasing chain length. With only one exception, all of the products were five-membered lactones.220 In the case of n = 3, the cyclization occurs in the side chain, again forming a five-membered ring. 

The reaction shown in Scheme 2-7 is an example of 1,3-asymmetric induction. The oxidative hydroxylation of a five-membered lactone led to an a-hydroxyl product 14.14 The a-hydroxylation of carbonyl compounds is further discussed in Chapter 4. 

Cyclic alkynyl carbonates undergo carbonylation in the presence of a palladium catalyst and carbon monoxide (5 MPa) in MeOH to give allenic carboxylates (Eq. 9.118) [92], Bu3P proved superior to Ph3P as the catalyst ligand. An enynyl cyclic carbonate underwent double vicinal carbonylation at 80 °C to produce a five-membered lactone product in 52% yield (Eq. 9.119). When the reaction was performed at 50 °C, the bicyclic enone lactone was produced in 75% yield along with 10% of the y-lactone. 

Unsaturated lactone 74 (Scheme 7.21) can be viewed as an oxygen heterocyclic analogue of 2-cyclohexenone, and it has recently been reported that catalytic 1,4-additions of Et2Zn to 74 can indeed be accomplished with high enantioselectivity. For adduct 76, Reetz achieved a remarkable 98% ee when employing ferrocene-based diphosphonate ligand 23 [48]. Using diphosphite 24, Chan et al. achieved an ee of 92% for the six-membered lactone 74 and a 56% ee for the five-membered lactone 25 [49c]. 

FIGURE 11.7 Cardiac glycosides consist of a sugar, a steroid skeleton, and a lactone ring. A five-membered lactone ring as here occurs in the cardenolide type. 

Epimerization of etoposide The anticancer agent etoposide contains a five-membered lactone function that is significantly strained because it is trans-fused. This material is readily converted into a relatively strain-free cw-fused system by treating with very mild alkali, e.g. traces of detergent, and produces an epimer (see Section 3.4.4) called picroetoposide. This isomer has no significant biological activity. 

Solid base catalysts were tested for this reaction, which was carried out in benzene as a solvent at 313 K. Among them, MgO, CaO, and SrO exhibited good catalytic properties, affording phthalide exclusively with yields between 86% and 100% after a short time (15min) in a batch reactor, whereas with y-alumina, phthalide was obtained with excellent yields and selectivity after 4h. The Tishchenko reaction of 2,3-naphthalenedicarbaldehyde was also carried out with CaO and with y-alumina at 333 K yields of the corresponding five-membered lactone were 94% and 100% after 2 and 20 h, respectively. 

Aldonolactones are commercially available at low cost, when compared to most of the common monosaccharides. They are typically synthesized by selective anomeric oxidation of unprotected aldoses with bromine [6]. Usually the thermodynamically more stable five-membered lactone (y-lactone) predominates over the six-membered form, with the exception of o-gluconolactone, which crystallizes as the 1,5-pyranolactone (5-lactone) [7] (Scheme 1). Another method for the preparation of sugar lactones is the dehydrogenation of unprotected or partially... 

Five-membered lactones (y-butyrolactones) fused to carbohydrates have proven to be convenient synthons towards branched-chain sugars through opening of the lactone unit. Velaskes et al. [208] described the synthesis of y-butyrolactones... 

With respect to five-membered lactones fused to hexopyranose units, some approaches have been reported so far and the exploitation of their synthetic potential has led to the access of new carbohydrate derivatives. Bicyclic derivatives of this type are key intermediates in the synthesis of the epimer at C-3 of the sugar moiety contained in miharamycins [212, 213]. The latter are antibiotics known to inhibit strongly Pyricularia oryzae, which produces the rice blast disease. These compounds are also considered to be a potential bioterrorism agent (Scheme 42). Hence, the 3,3-spiroepoxide 176 was converted into the 3-C-cyanomethyl derivative 177, the hydrolysis of which led to spontaneous cyclization in the presence of... 

Berti and Bottari l s 149 reported that epoxidation of o-carboxy-tmns-Htilbcnc with per benzoic add is a Btoreospccific reaction that can yield either of two lactones (XLII) and (XLITT), depending ou the temperature (Eq. 42). Two lactones (XLlV) and (XLV) can likewise be formed from the corresponding ets-stilbene derivative, the predominance of one over the other being again temperature-dependant (Eq. 43). The five-membered lactones (XLII) and (XLIV) appear (i> be favored at low temperatures. 

Certain uneaturated fatty acids give lactone esters on treatment with peracetic acid, presumably by intramolecular attack of the carboxyl function on the initially-formed epoxide ring. Thus, 4,8-cpnxypentanoic acid generated by peracetic add oxidation of 4 pentenoie acid undergoes cleavage to give a five-membered lactone as... 

The five-membered lactone 58 reacts similarly under the same conditions (77KGS1479). 

Following is a structural formula of 5-hydroxypentanoic acid and the five-membered lactone (cyclic ester) it forms. 

The work reported by Eaton and coworkers can be summarized as reactions where an allene system in conjugation with a further unsaturated functionality reacts with carbon monoxide in the presence of an iron-carbonyl complex such as Fe(CO)5 under photochemical and thermal conditions when Fe2(CO)9 is used. When diallenes are used (X=R2C=C, Scheme 9.24), five-membered carbocyclic products are obtained [51, 52], whereas when allenyl ketones (X = O) are applied, five-membered lactones are generated [53, 54]. The use of allenylimines (X = NR) leads to five-membered lactams under these conditions [55]. 

The C=N bonds of isocyanates [27] and Schiff bases 83 [28] react with butadiene to give the piperidone 82 and piperidines 84. The nucleophilic attack of CO2 to the amphiphilic bis-n-allylpalladium 68 generates the n-allylpalladium carboxylate 85, from which the six-membered lactone 86 and five-membered lactone 87 are obtained under certain conditions [29-31]. The unsaturated ester 88 is also formed. 

The IR, NMR, and mass spectra of daphmacrine (18) suggest that it has a nitrogen heterocyclic skeleton similar to that of daphniphylline (1) but differs in the oxygen-containing moiety. The IR spectrum of this alkaloid showed two carbonyl bands at 1770 and 1730 cm-1 resulting from a five-membered lactone and an ester group, respectively. The NMR spectrum showed the presence of two tertiary methyl... 

From a biogenetic point of view, the most important point is that the oxygen heterocyclic moiety in 18 consists of a six-membered ring in the chair form bridged by carbon and oxygen atoms to form a five-membered lactone with methyl groups substituted at each bridgehead as compared with the ketal moiety of daphniphylline (1) (Section V). 

Daphmacropodine [19 mp 215-218° (as hydrobromide) [a]D +4.9° (in CHC13) m/e 513, 286, and 272] has also been isolated from the bark of D. macropodum together with daphmacrine (18). This alkaloid has an acetoxyl group (pmax 1740 and 1240 cm-1) but any IR absorption band resulting from a five-membered lactone, which can be found in the case of the alkaloid 18, is not observed. The NMR spectra of both alkaloids are quite similar except for the appearance of a singlet at 4.78 in daphmacropodine which can be assigned to the one proton of... 

By use of chelating tri- and tetramines 59 or 60 Kharasch additions can be performed in 65-75% yield using 0.3-10 mol% FeCl2 as the catalyst (Fig. 13) [116, 117]. The same catalysts are very efficient to promote otherwise difficult ATRC of co-alkenyl trichloroacetates 58 providing five-membered lactone 61 by 5-exo cycli-zation in 55% yield and eight- to ten-membered lactones 62 by 8-10-endo cyclizations in 34-50% yield, respectively. Even oo-allyl oligo(ethyleneoxy) trichloroacetates underwent radical macrolactonization reactions in 56-60% yield with 10 mol% of catalyst. 

The reaction can also be carried out intermolecularly, i.e., between internal acetylene, ketone and CO. This [2+2+1] cycloaddition in the presence of Ru3(CO)12 leads to the formation of unsaturated five-membered lactones (Eq. 107) [168,169],... 

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