Lactone, nucleophilic ring opening

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

Employing an excess of the organometallic reagent (2 equiv) at 100 °C resulted in the formation of ketopyrrole (S)-79 in 87% yield. Obviously, compound (S)-79 is produced by successive N-acylation, t>-directed metallation and N,C-acy migration. Nucleophilic ring-opening reaction of the lactone (S)-77 with A -methylpyrrole lithiated in 2-position (with Bu Li/TMEDA) proceeded smoothly furnishing the ketone (S)-79 in 62% yield. 

On the action of BF3, a steroid oxirane undergoes rearrangement to a tetrahydro-furan. 7-Lactones are formed from oxirane by nucleophilic ring-opening (Eqs. 192-194). ° ... 

Fujisawa [63] reported the nucleophilic ring-opening reaction of five- and six-membered lactones with Grignard reagents by a copper catalysis [Eq. (50) and Table 12]. 

Lactone 35 was obtained exclusively on treatment of diethyl 2-vinylcyclopropane-l,l-dicarbox-ylate (34) with bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic acid 2,3 5,6-dianhydride (BTA) in refluxing 1,2-dichloroethane. Other Lewis acids lead to protonation product 36 and (or) products of nucleophilic ring opening 37. °... 

Lactones are common subunits in natural products and are therefore of high biological relevance. An approach to 7- and 5-lactones starts from Merrifield resin-bound to-alkenoic acids 99 (Scheme 26). Epoxidation and nucleophilic ring-opening of the oxiranes 100 produced the hydroxy acids 101, which cyclized upon treatment with trifluoroacetic acid to give five- and six-membered lactones 102. Treatment of the epoxides 100 with trifluoroacetic acid provided the lactone 102 (Nuc = OH) [41],... 

Nucleophilic ring-opening of epoxide 53 with Grignard reagent 55 in the presence of cuprous iodide affords 56. A Mitsunobu inversion of the free hydroxy group followed by lactonization and conversion to an or /io-lactone provides 57. 

Nucleophilic ring opening of the lactone ring in bicycloadducts of type 5 leads directly to tetrasubstituted cyclohexenes in which the relative stereochemistry of all four contiguous stereocenters is established. Thus, pyrones provide attractive synthetic equivalents to acyclic dienes of type 6 which may be difficult to prepare as pure geometrical isomers and which in many cases do not lead via Diels-Alder cycloaddition to the desired stereochemical relationships. The application of [4+2] cycloaddition reactions of 2-pyrones to synthesizing functionalized cyclohexenes was the partial subject of a 1994 review. ... 

A potentially important method for the synthesis of 6>-unsaturated esters from saturated lactones has been reported by two groups. This entails nucleophilic ring opening of the lactone by sodium phenyl selenoate followed by oxidative removal of the selenium. (Scheme 34). 

A few examples of base promoted domino ring opening lactonization of epoxides with active methylene compounds (malonate, cyanoacetate, acetoacetates) are known earlier in the literature [42]. Pizzo s group has recently described domino nucleophilic ring opening of epoxides by active methylenes, catalyzed by polymer-supported bases, under solvent-free conditions (SolFCs) (Scheme 4.24)... 

Transition metal catalyzed ring expansions of cyclic ethers to lactones under pressures of CO [51, 52] have been reported for tetrahydrofuran [53], oxetanes, and epoxides [54—56]. Carbonylation of epoxides is particularly important since P-lactone products are challenging synthetic targets (see Section 2.2.5). Using Co(CO)4 in combination with a Lewis acidic Al-salen counterion, the reaction of (R)-propylene oxide and CO occurs with stereochemical retention (Scheme 2.23) [57]. The mechanism is believed to involve Lewis acid activation of the epoxide followed by nucleophilic ring opening with Co(CO)4 [58]. 

Scheme 12.10 Cyclic carbonate and lactone monomers and their active sites in nucleophilic ring-opening polymerization.

Treatment of carboxyaldehydes 252 with hydrazine hydrate in ethanolic KOH under refluxing conditions provides an easy entry to the novel imidazo[2,l-4][l,3]thiazole fused diazepinones 253 via lactone ring opening by intramolecular nucleophilic attack of the amino group of the intermediate hydrazone which could not be isolated (Equation 31) <2006TL2811>. 

---