Phosphonate, lactone

The reaction of perfluoroalkyl iodides with alkenes affords the perfluoro-alkylated alkyl iodides 931. Q.a-Difluoro-functionalized phosphonates are prepared by the addition of the iododifluoromethylphosphonate (932) at room temperature[778], A one-electron transfer-initiated radical mechanism has been proposed for the addition reaction. Addition to alkynes affords 1-perfluoro-alkyl-2-iodoalkenes (933)[779-781]. The fluorine-containing oxirane 934 is obtained by the reaction of allyl aicohol[782]. Under a CO atmosphere, the carbocarbonylation of the alkenol 935 and the alkynol 937 takes place with perfluoroalkyl iodides to give the fluorine-containing lactones 936 and 938[783]. 

Mitsubishi have reported several processes based on Ru-catalyzed hydrogenation of anhydrides and acids. Succinic anhydride can be converted into mixtures of 1,4-butane-diol and y-butyrolactone using [Ru(acac)3]/trioctylphosphine and an activator (often a phosphonic acid) [97]. Relatively high temperatures are required ( 200°C) for this reaction. The lactone can be prepared selectively under the appropriate reaction conditions, and a process has been developed for isolating the products and recycling the ruthenium catalyst [98-100]. 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Table 3.20 lists examples of the preparation of oxygen-containing heterocycles by RCM. Further examples, including lactones [895], pyrans [896,897], chromenes [839], tetrahydrofurans [838], phosphonates [898], and oxepines [856,899-902], have been reported. For references to macrocyclizations see Scope and Limitations in this section. 

Reaction of the anion from phosphonate (5-1) with ethyl meta-triflurophenoxy-methylacetate results in acylation of the phosphonate by the displacement of ethoxide and the formation of (5-3). Condensation of the yhde from this intermediate with the biphenyl ester at position 11 of Corey lactone (5-4) leads to the enone (5-5) with the usual formation of a tmns olefin expected for this reaction. The very... 

The analogue in which carbon replaces oxygen in the enol ring should of course avoid the stability problem. The synthesis of this compound initially follows a scheme similar to that pioneered by the Corey group. Thus, acylation of the ester (7-2) with the anion from trimethyl phosphonate yields the activated phosphonate (7-3). Reaction of the yhde from that intermediate with the lactone (7-4) leads to a compound (7-5) that incorporates the lower side chain of natural prostaglandins. This is then taken on to lactone (7-6) by sequential reduction by means of zinc borohydride, removal of the biphenyl ester by saponification, and protection of the hydroxyl groups as tetrahydropyranyl ethers. 

In a similar double carbonylation process 2-(propargyl)allyl phosphonates were converted into condensed, unsaturated lactones under anhydrous conditions (3.36.),44... 

The construction of the C2-C3 bond of the 1-hydroxyethylene moiety by the addition of a two-carbon fragment to aminoalkyl epoxides, amino ketones, p-amino-a-hydroxy aldehydes, or 4-amino-3-oxo phosphonates was also studied. As summarized in Scheme 14, Evans et al.[28] added a malonate to an aminoalkyl epoxide and the product spontaneously cyclized, leading to a lactone.— Then, the second side chain was incorporated into the a-carbon of the lactone, providing a mixture of C2 epimers. The final compound was obtained by hydrolysis and decarboxylation. The lack of diastereoselectivity of this method is offset by the small number of steps and the accessibility to all eight possible stereoisomers. Biihlmayer et al.[30] also used a similar method, but they transformed the epoxide into the apparently more reactive iodide. Then, the iodide compound was treated with an enolate. 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

Reactions of carbocyclic P-keto esters, sulfonium ylides and enamines with activated alkynes such as DMAD are known to result in formation of (n + 2) ring expanded products. In a study of the analogous reactions of carbocyclic p-keto phosphonates, it was found that in the cases of the simple cyclic P-keto phosphonates 1, ring expansion occurred to give 2 in reasonable yield. Extension of the method to the tetralone 3, however, led to formation of two products, the "expected" (n + 2) ring expansion product analogous to 2 (37%), and the lactone 4 (29%). 

The applications of re-acidic chiral stationary phases include the resolution of a-blockers and /1-blockers, amines, arylacetamine, alkylcarbinols, hydantoins, barbiturates, naphthols, benzodiazapines, carboxylic acids, lactams, lactones, phthaldehydes selenoids, and phosphorus compounds. Hyun et al. [16] achieved a chiral resolution of a homologous series of iV-acyl-x-(l-naphthyl )cthylaminc on AA(3,5-dinitrobenzoyl-(i )-phenylglycine and N-(3,5 - dini tr o ben zoy I)-(,S ) -1 c u c ine CSPs. The authors used hexane-2-propanol (80 20, v/v) as the mobile phase. Similarly, the scope of re-basic CSPs comprises the chiral resolution of / -blockers, amino acids, amines, diamines, amino phosphonates, naphthols, benza-diazapines, carboxylic acids, hydroxy acids, dipeptides, tripeptides, diols,... 

Phosphonate ester 30 can also be considered as a mimic of the transition state for subsequent esterolysis and aminolysis of the 8-lactone. In fact, the antibody that promotes ring formation was shown to catalyze the stereoselective reaction between 29 and 1,4-phenylenediaminc.39 The kinetic mechanism of the bimolecular process involves random equilibrium binding of lactone and amine, and the observed turnover rate could be approximated from the measured difference between the binding of reactants and the TSA. Again, entropic factors are presumed largely responsible for the observed rate acceleration, with minimal contributions derived from specific catalytic groups at the active site. 

Intramolecular Carbon-Hydrogen Insertion. The advantages of rhodium(II) catalysts for carbenoid transformations are nowhere more evident than with carbon-hydrogen insertion reactions. Exceptional regio- and diastereocontrol has been observed for Rh2(OAc)4 catalyzed transformations of a broad selection of diazoketones, a-diazo-p-ketoesters, a-diazo-P-keto-sulfones and -phosphonates which yield cyclopentanone derivatives in moderate to good yields (57-54). In contrast, poor yields and low regioselectivities characterize the corresponding copper catalyzed reactions. Applications of dirhodium(II) catalysts for C-H insertion reactions have even been extended to the synthesis of y-lactones (55), 3(2//)-furanones (56,57), P-laetones (58), and P-lactams (59,60). 

The synthesis of latanoprost (1) commences with the lactone 5 derived from the Corey lactone (Scheme I).11 12 The early introduction of the p-phenylbenzoyl protecting group12 in this lactone affords crystalline intermediates in the synthesis that are easy to handle and purify. In the next step, the primary alcohol functionality in the lactone 5 was oxidized using Pfitzner-Moffat conditions (DCC, DMSO and phosphoric acid) to yield the aldehyde 6. The crude aldehyde was then treated with dimethyl (2-oxo-4-phenyl)-phosphonate under Wadsworth-Emmons conditions (NaH, DME) to afford the enone 7 as a white crystalline solid in 59% yield. 

Dioxins behave as masked cis y-hydroxy enones and as such are an excellent source of y-lactones, notably in an enantio-enriched form <02JOC5307>. Treatment of the dioxin with an amine base results in rearrangement to 1,4-dicarbonyl compounds from which pyrroles and thiophenes are available in a one-pot synthesis <02TL3199>. Stabilised phosphonates add to 1,2-dioxins to yield diastereo-pure substituted cyclopropanes <02JOC3142>. 

---