Cyclization reactions 3-lactone synthesis

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>. 

The following contribution is intended to continue our earlier review [6] dealing with the then known cesium assisted ractions only some very important earlier cesium assisted reactions are described here for the sake of completeness After a short description of the properties of some cesium compounds used in this respect in organic synthesis, those reactions are discussed that have been published more recently and which proceed under the intermediate formation of organic cesium salts at oxygen, nitrogen or sulphur functions. Only those cyclization reactions are considered which allow a direct comparison of the yields obtained with cesium compounds or cesium metal. The description starts with reactions leading to the formation of C—C bonds and proceeds to the syntheses of ethers, lactones, amines and sulfides. The discussion ends with a summary of the attempts to explain the cesium effect . 

Over the past twenty years, the intramolecular allylation of aldehydes has been used in the synthesis of natural products containing a-methylene-y-lactones [95-101] (e.g. confertin [99] and cembranolide [100, 101]), polyene-containing macro-lides [102, 103] (e.g. asperdiol [102]) and, more recently, cyclic ether containing natural products (e.g. (-i-Vlaurencin [104] and hemibrevetoxin B [105]). However, the principles that govern the stereoselectivity in these cyclization reactions have only recently been studied in a systematic manner (see below). 

Oxime ethers and imines are viable intramolecular radical acceptors. Advanced precursors of (—)-tetrodotoxin were prepared via radical cyclization reactions using oxime ethers as radical acceptors [105]. In the synthesis of (+)-7-deoxypancratistatin (160) [106] (Scheme 55), the intermediate 159 was prepared via tandem radical cyc-lizations of the precursor 158 possessing an A -aziridinylimine and an 0-benzyloxime moiety. Direct formation of lactones is possible as shown in the reaction of the (2,2-diphenylhydrazono)acetate 161, which afforded the hydrazino lactone 162 along with the epimer 163. (-t-)-Furanomycin (164) was synthesized from 162 [107] (Scheme 56). Normally, use of nitrile radical acceptors is limited to cyclopentanone synthesis, but the rigidity of the 1,6-anhydro scaffolding in the bromide 166 enabled radical cyclization to give the tricyclic ketone 167, which comprises the entire skeletal framework of tetrodotoxin [108] (Scheme 57). 

A number of oxacyclic natural products were synthesized via carbocycle-forming radical reaction of oxacyclic intermediates. An early example is the synthesis of (-)-dihydroagarofuran (170) by Biichi [109] (Scheme 58). The bridgehead chloride 168 obtained from the corresponding hydroxy ketone was amenable to radical cycliza-tion, and the tricyclic ether 169 was duly obtained. The aplysin synthesis [110] provides another example, and (—)-karahana ether (173) was synthesized via radical cyclization of the substrate 171 [111] (Scheme 59). Lactonic natural products (-1-)-eremantholide A [112], alliacolide [113], and (-)-anastrephin [114] were prepared via a variety of carbocycle-forming radical cyclization reactions. In the total synthesis of spongian-16-one (176) [115] (Scheme 60), the butenolide moiety in the substrate 174 served as the final radical acceptor for three consecutive 6-endo-. rig cyclizations. 

In a study of micelles on cyclization reactions, iV-hexadecyl-2-chloropyridinium iodide was used as an amphiphilic carboxy activating agent for lactonization and lactamization procedures (94JOC(59)415>. Ferricyanide oxidation (Decker oxidation) of 1-substituted polyarylpyridinium salts (2,4,6-triaryl, 2,3,4,6-tetraaryl, and pentaaryl) have been found to provide a general approach to synthesis of substituted pyrroles (94H(37)1347>. 

A microemulsion of low water content has been found to be an excellent medium for synthesis of long-chain lactones [97]. These compounds, which are important perfume ingredients, are not easily made by conventional organic synthesis because intermolecular esterification dominates over intramolecular esterification. In the microemulsion, the molecular arrangement at the oil/water interface seems to favor the cyclization reaction (Fig. 15). 

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. 

Shiina accomplished the total synthesis of pseudo 7b by a key cyclization reaction to form the nine-membered ring, which was efHciendy achieved by their original mixed-anhydride method promoted by MNBA under basic catalysis (Scheme 5.37) [89]. Lactonization of the seco-acid 100 was carried out in the presence of MNBA and DMAP, and the desired monomeric lactone 101 was obtained in 71% yield along with the dimeric lactide 102 (7%) [36, 37]. 

These -condensation products are useful in organic synthesis. For example, the vinylsilane portion of the molecule can be used as an internal nucleophile in cyclization reactions, as demonstrated in the synthesis of substituted aromatic compounds (eq 3). They can also be used as lactone precursors (eq 4), as demonstrated in the synthesis of the steroidal IT-spiro-y-lactone (2). ... 

SCHEME 22 y-Methylene-y-lactone synthesis via Au-catalyzed cyclization reaction. 

Lactone rings have also been constructed using carbonylation of appropriately functionalized compounds by the insertion of carbon monoxide. Ryu, Sonoda et al. have reported the synthesis of 8-lactones from saturated alcohols and carbon monoxide via remote carbonylation [110,111] (Scheme 64). Treatment of saturated alcohol 292 with lead tetraacetate led to oxygen-centered radical 293, which underwent a 1,5-hydrogen transfer reaction to produce carbon-centered radical 294. Trapping of this radical with carbon monoxide and oxidation followed by cyclization gave lactone 297. 

Vespa orientalis, the Oriental hornet, produces lactone (428) (Scheme 77), which is thought 183) to control some aspects of social behavior. The / -(+)- and 5-(-)-enantiomers (428a and 428b, respectively) were elaborated by Coke and Richon 184) from 1-tridecene (422) via amino-alcohol (424), which was resolved into its enantiomeric forms by resolution of the optically active dibenzoyl tartarates (Scheme 77). Hofmann elimination followed by reaction with propiolic acid dianion (425) and reductive cyclization completed the synthesis. 

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