Lactone annulation

Whereas lactone annulation invokes a relief of strain of the four membered ring by migration of the ring bond to an electron deficient oxygen, a similar migration to an election deficient carbon creates a cyclopentanone synthesis (Eq. 73). The release of approximately 84 kJ/mole (20 kcal/mole) provides a strong driving force. Thus, the 1,1-cyclobutanone annulation of ketones translates into a 1,1-cyclopentanone annulation. 

The availability of cyclopentenones from butanolides allows the lactone annulation to facilitate the synthesis of cyclopentyl natural and unnatural products. An example that highlights the latter is dodecahedrane (178) for which 179 constitutes a critical synthetic intermediate 136,137). Lateral fusion of cyclopentenones as present in 179 can arise by acid induced reorganization and dehydration of 180. While a variety of routes can be envisioned to convert a ketone such as 182 into 180, none worked satisfactorily137 On the other hand, the cyclobutanone spiro-annulation approach via 181 proceeds in 64 % overall yield. Thus, the total carbon cource of dodecahedrane derives from two building blocks — cyclopentadiene and the cyclopropyl sulfonium ylide. 

The Helquist approach to quadrone begins in the same fashion and has many close similarities to the Danishefsky effort. Importantly, however, a key element of novelty in Scheme LIII is the deplopment of a lactone annulation procedure which bypasses the regiochemical complications earlier encounter . 

In 1992, Trost and his co-workers investigated desymmetrization of cyclic w j-o-diesters with lithium sulfonyl-methylenenitronate as a nucleophile in the presence of Trost s ligand 118, where the corresponding cyclic compounds are obtained with an excellent enantioselectivity via intramolecular cyclization (Scheme 15),103,103a Asymmetric cyclopropanation and lactone annulation are achieved according to this protocol (Scheme Nitroalkanes can also be employed as carbon-centered nucleophiles in lieu of malonates (Scheme 17). ... 

The total synthesis of the immunosuppressant (-)-pironetin (PA48153C) was accomplished by G.E. Keck and co-workers. The six-membered a,(3-unsaturated lactone moiety was installed using a lactone annulation reaction by reacting the advanced aldehyde intermediate with the lithium enolate of methyl acetate. The aldehyde was prepared by the Ley oxidation of the corresponding primary alcohol and was used without purification in the subsequent annulation step. 

Lansbury, P.T., and Vacca, J.P, Superior methodology for y-lactone annulation. Intramolecular alkoxyhydride reduction of conjugated nitriles. Tetrahedron Lett., 23, 2623. 1982. 

Keck et al. have used the lactone annulation procedure developed in their laboratory to install the lactone moiety by reaction of the lithium enolate of methylacetate with a (3-acetoxy aldehyde [108]. The other key steps include a diastereoselective Lewis acid mediated (Z)-crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction and an arari-selective Sml2 reduction of a p-hydroxyketone. The preparation of the C8-C15 fragment of (-)-pironetin started with the chelation-controlled addition of (Z)-crotyl tri-n-butylstannane to the (3-benzyloxy-aldehyde 153 in the presence of TiCU [109] to give the... 

Cyclizations of enediynes under the action of electrophiles 13KGS129. Cyclization reactions of l,l-bis(trimethylsilyloxy)ketene acetals (synthesis of lactones, cyclic anhydrides, lactone-bridged N-heterocycles, lactone-annulated N-heterocycles) 12SL1283. 

The 1,3-dipolar cycloaddition of a variety of nitrile oxides, nitrones, ethyl diazoacetate, and azomethine ylide to the chiral furanone 174a was studied with respect to the present regio- and diastereoselectivity (93T8899). In the case of the azomethine ylide addition, three stereoisomeric adducts were obtained. However, in the case of the other dipoles only two stereoisomeric adducts were isolated the major product proved to be the an//-facial isomer. In this way, a number of multifunctional (lactone-annulated) isoxazolines 241 and 242, isoxazolidines 243 and 244, pyrazolines 245a,b, and pyrrolidines 248a,b,c could be synthesized (Scheme 65) (93T8899). 

Kido, F., K. Tsutsumi, R. Maruta, and A. Yoshikosi Lactone Annulation of p-Keto Esters with p-Vinylbutenolide and the Total Synthesis of Racemic Frullanolide. J. Am. Chem. Soc. 101, 6420 (1979). 

Related and regioselective processes have been exploited in the preparation of novel lactone-annulated steroids (eq 98). ... 

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