Alkenyl carbonylative lactonization

Termination of cyclic carbopalladation of alkynes via carbonylative lactonization/ lactamization has been achieved with alkenyl iodides containing an ca oxydryl or amido/amino moiety [85]. 

A synthetic application of the sonolysis of iron carbonyls is the preparation of useful ferrilactones. The alkenyl epoxides (2, R = H, Ph, 1-hexanyl) are smoothly converted to the corresponding ferrilactone complexes (3) on reaction with Fe2(CO)9 suspended in THF and sonicated at room temperature [53]. Such complexes undergo several synthetically useful transformations (Scheme 3.7) including oxidation with Ce(IV) as a route to P-lactone natural products or P-lactam antibiotics and reaction with CO to afford 5-lactones [54]. Somewhat surprisingly this reaction is efficient even in diethyl ether, a volatile solvent which delivers low cavitation energy. 

When employing enantioenriched l-titano-2-alkenyl carbamates 334 in carbonyl addition, the selectivity depends on the enantiomeric purity that was achieved in its preparation (see Section IV.C.l). The (ii)-crotyl derivative (R)-334a has been employed several times (equation 92)224,252,253 optically active homoaldol products 346 are easily converted into y-lactones 347 by four different pathways, which require an oxidation step (see Section IV.C.6). Appfications in target synthesis include the natural products (-b)-quercus... 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

Asymmetric carbonylation of alkenyl halides a-methylene lactones Optically active a-mcthylene lactones can be prepared by carbonylalion of alkenyl halides such as I catalyzed by PdCI2-(R)-BINAP (5 mol %) in the presence of thallium acetate. 

Double carbonylation As a radical mediator in the carbonylation of 4-alkenyl iodides, BujGeH behaves differently from BUjSnH, because it is a slower hydrogen donor, giving the second acyl radical time to react with the cyclic ketone, which was formed in the first step. Instead of the keto aldehydes, fused y-lactones become the major products. 

The 5-keto acid 11 is supposed to be formed by hydroboration and oxidation of the terminal CC double bond in 12, feasible by allylation of the enone 13. Enone 13, once again, originates from an intramolecular Knoevenagel alkenylation of the a,5-diketone 14 prepared by addition of ethylmagnesium halide to the enol lactone 15 of the 5-keto acid 16. Preceding this keto acid, the allyl compound 17 is formed by nucleophilic opening of the cyclopropane ring with hydride and mefliylation in a position of the carbonyl in the cyclopropyl ketone 18. 

The carbonylation of p-lactones to form succinic anhydrides also occurs with catalysts containing a combination of the salen-ligated aluminum Lewis acid and cobalt carbonyl anion (Equation 17.47). These reactions occur with lactones bearing alkyl, alkenyl, and ether substituents, as well as with the unsubstituted p-propiolactone. All of these substrates... 

Formation of /3-lactones throngh these procedures is rare carbonylation of alkenyl oxiranes gives these products in low yields. AUyl carbonates may also serve as precursors to butyrolactones in a method developed by Tamaru et al. A protic solvent such as ethanol gives a ca. 1 1 mixture of the isomerized o,/3-unsaturated lactone and the acyclic ester, whereas an aprotic solvent (e.g., dioxane, THF, benzene) leads exclusively to the expected lactone (Scheme 12). 

Carbonylation procedures were explored and applied in phthalide synthesis as well. In 1986, Negishi and co-workers studied the palladium-catalyzed cyclization of o-iodoatyl alkenyl ketones. By using Pd(dba)2 as the catalyst, bicyclic and polycyclic quinones could be produced in high yields. Interestingly, phthalides were formed when using Pd(OAc)2/PPh3 as the catalyst system (Scheme 2.159). Afterwards, the group carried out systematic studies on this topic. Lactones and lactams were produced selectively from various substrates. 

Use of the Sharpless epoxidation allows access to optically active alkenyl epoxides and both the reaction with diiron nonacarbonyl under sonolytic conditions and the subsequent carbonylation proceed with retention of configuration, thus allowing us to predetermine the stereochemistry at of the 5-lactone at the C5-centre (Scheme 125). 

Intramolecular [80] and intermolecular [81,82] trapping of acylpalladium intermediates with enolates has been studied. Intermolecular versions can involve trapping with both C- and 0-enolates. The Pd-catalyzed carbonylation reactions of alkenyl iodides in the presence of various ketone enolate precursors displayed an interesting dichotomy the expected 0-enolate trapping product 47 may undergo cyclization to give six-membered lactone 48, and the product s composition critically depends on the amount of a base and the structure of ketones (Scheme 9.19). 

Suzuki, T., Uozumi, Y. and Shibasaki, M. (1991) A Catalytic asymmetric synthesis of a-methylene lactones by the palladium-catalysed carbonylation of prochiral alkenyl halides. Journal of the Chemical Society, Chemical Communications, 1593-1595. 

A mild conversion of carbonyl derivatives, including lactones, into alkenyl silanes has been reported. For example reaction of 5-0-/err-butyldimethylsilyl-2,3-0-isopropylidene-D-l, 4-ribonolactone with tris(trimethylsilyl)titanacyclo-butane gave product 36. ... 

---