Cyclization of enolates

The intramolecular cyclization of enolate of l-tryptophyl-3-((3-ketobutyl) pyridinium bromide (160) afforded enamine 161, which undergoes stereoselective acid cyclization with cone. HCl to give the pentacyclic ketone 162 (Catalytic hydrogenation of 162 led to (d,l)-pseudoyohimbone (163) (76JA3645). Again, H3-H15 were found to have the tmns configuration in 162. 

Geometric factors in the TS are also responsible for differences in the case of cyclization of enolates 9 and 10.84... 

Given the large number of tandem cyclization processes that have been explored [63], it is disappointing to note that so few have been promoted electrochemi-cally. There appears to be a significant opportunity for additional exploration. Two tyiws of tandem cathodic cyclizations are discussed below. The first involves generation of a ketyl, and its subsequent cyclization onto a pendant alkene to afford a new radical that closes onto a second alkene [64,65]. The second focuses on chemistry not yet discussed involving the reductive cyclization of enol phosphates of 1,3-dicarbonyl compounds [66]. 

The electrochemical cyclization of enol ethers in methanol uses an undivided cell and 2,6-lutidine is added as a proton scavenger. Acid catalysed hydrolysis of the enol function is thus avoided. An advantage is gained by diluting the methanol witli a non-nucleophilic co-solvent. This lowers the extent of dimethoxylation of... 

One of the factors directing the alkylation of an enolate is the Jt-facial selectivity. The differences in reactivity of the two diastereotopic faces of the enolate, due to steric and electronic features, contribute to the steric control of the alkylation (for extensive reviews, see refs 1, 4, and 30). Likewise, stereoelectronic features are important control elements for C- versus O-alkylation, as illustrated by the cyclization of enolates 1 and 3 via intramolecular nucleophilic substitution 39. 

In a complementary approach, the stereocontrolled [4-exo-tet] cyclization of enolates (71) in which the nucleophilic species attack from the C4-position of the p-lactam ring to be formed has been reported [77] (Scheme 17). B3LYP/6-311+ +G calculations showed that the enolates (71) are preferred with respect to enolates (72) thus resulting in the formation of (3-lactams (3S,4)-(73). 

An acid-mediated Prins type cyclization of enol ether 328 followed by basic hydrolysis of the intermediate trifluoro-acetate provides a key step during synthetic studies toward leucascandrolide A (Equation 139) <20010L755>. The acid-promoted Prins cyclization of enol ethers attracts much attention <20030L1499, 2004HCA2750, 2005OL2683>. 

The same research group has also developed the ruthenium-catalyzed inter-molecular addition of carboxylic acids to carbon-carbon triple bonds [4]. When a-hydroxy acids 3 were employed with terminal alkynes, 1,3-dioxolan-4-ones 5 were synthesized via cyclization of enol ester intermediates 4 (Eq. 2) [5]. 

The intramolecular mercury-induced cyclization of enol ethers has proven useful for the dia-stereoselective preparation of disaccharides. The reaction is carried out by treating the enol ethers (e.g., 7) with mercury(ll) trifluoroacetate in tetrahydrofuran for 2 hours at 0 °C, followed by reaction with aqueous potassium chloride at 0 °C for 1 hour. The chloromercury derivatives are obtained in good yield and only one isomer can be detected in the reaction mixture95-96. 

Szell, T., Schobel, G., Balaspiri, L. Cyclization of enol esters of o-acyloxyphenyl alkyl ketones. II. A contribution to the mechanism of the reaction. Tetrahedron 1969, 25, 707-714. 

For related palladium-catalyzed cyclizations of enolates, see Ciufolini, M.A. Qi, H.B. Browne, M.E. Intramolecular arylations of soft enolates catalyzed by zerovalent palladium. J. Org. Chem. 1988, 53, 4149 151. Muratake, H. Natsume, M. Nakai, H. Palladium-catalyzed intramolecular -arylation of aliphatic ketone, formyl, and nitro groups. Tetrahedron 2004, 60, 11783-11803. Muratake, H. Natsume, M. Palladium-catalyzed intramolecular -arylation of aliphatic ketones. Tetrahedron Lett. 1997, 38, 7581-7582. 

DMSO complexes have also been prepared and studied in contexts related to organome-tallic chemistiy. DMSO binds to low-valent late metals through the electron pair on sulfur, to harder high-valent metals through the electron pairs on oxygen, and to some complexes with a mixture of 0- and S-bound forms. " Palladium complexes of DMSO and of biden-tate sulfoxide ligands have been used as catalysts for the oxidative cyclization of enols and... 

Examples of intramolecular oxidative cyclizations promoted by Cu(OTf)2 include cyclization of enolates of diketones and diesters (eq 4) and oxidative cyclization of hydrolytically resistant, s-and ,( -unsaturated silyl enol ethers." For instance, (1) reacts with excess Cu20/Cu(0Tf)2 in MeCN to give a 90% yield of a 20 1 mixture of the trans-fused and cis-fused tricyclic ketones (2) and OHeqS)." ... 

A palladium-catalyzed intramolecular cyclization of enolate O-aiylation and thio-enolate S-arylation was reported by Willis and co-workers in 2006. A catalyst generated from Pd2(dba)3 and the ligand DPEphos effects the key bond formation to deliver a variety of substituted products from both cyclic and acyclic precursors. The analogous thio-ketones undergo C-S bond formation using identical reaction conditions and were converted to ben-zothiophene products. A cascade sequence that produces the required a-atyl ketones in situ has also been developed (Scheme 2.6). 

CYCLIZATION OF ENOL ETHERS 14 WITH TRIFLIC ACID... 

Regio- and stereo-selectivity have been studied for the cyclization of enolates derived from 4,5-, 5,6-, and 6,7-epoxy-l-phenylalkan-l-ones. Depending on the substrate and the cyclization procedure used, products of C- or D-alkylation were found. 

Regio- and stereo-selectivity in the intramolecular cyclization of enolates derived from 4,5-, 5,6-, and 6,7-epoxy-1-phenylalkan-l-ones (18a,b-2 a,b) has been explored. Competition between C- and O-alkylation routes have been discussed. The LHMDS-Sc(OTf)3 protocol seems to be a valuable tool for obtaining the corresponding y-hydroxy ketones stereoselectively from (18a,b) and (20a,b) whereas (19a,b) reacted cleanly only under alternative basic conditions, and yielded products of O-alkylation. 

Cyclization of enolate anions by intramolecular nucleophilic substitution is subject to an element of stereoelectronic control which determines whether C- or O-alkylation occurs. This can be illustrated by the following two reactions ... 

Semmelhack, M. F. and Bargar, T. M., Cyclizations of enolates onto aromatic rings via the photo-SrjjI reaction preparative and mechanistic aspects,/. Org. Chem., 42, 1481, 1977. 

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