Ynolates synthesis

A review on ynolates, including the synthesis of p-lactones, has appeared <03S2275>. Morita-Baylis-Hillman-type adducts have been converted into a-alkylidene-p-lactones 65, which on reaction with dimethyltitanocene can be transformed into 3-alkylidene-2-methyleneoxetanes <03OL399>. Lactones 66 have been obtained via the cinchona alkaloid-catalyzed dimerization of monosubstituted ketenes <03OL4745>. The PdCh-promoted synthesis of P-lactones 67 have been achieved via cyclocarbonylation of 2-alkynols <03OL4429>. 

The first synthesis of lithium ynolates was reported by Schollkopf in 1975. The isoxazolyllithium 10, prepared by lithiation of 3,4-diphenylisoxazole (9), undergoes fragmentation to yield the lithium ynolate 11 (equation Tf. The dilithium ynolate dianion 14 is also synthesized by the same protocol from 3-phenylisoxazole (12) via the 3-phenyl-5-isoxazolyllithium (13) intermediate (equation 3). The maximum yields were around 80%, judged by the yields of the /3-lactones (Section IV.A). 

Although this method is convenient in the laboratory, t- and i-BnLi are somewhat expensive and shonld be handled carefnlly, especially in a large scale. A more practical method for the synthesis of ynolates is the rednctive lithiation method. The dibromo esters 43 are treated with lithinm naphthalenide to give the ynolates 44 in good yield. Naphthalene-catalyzed reductive lithiation of the dibromo esters can also be performed, providing the ynolates more efficiently (equation 17) . 

Multisubstituted five-membered aromatic heterocycles are synthesized via this cascade protocol (equation 34). The cycloadditions of a-acyloxyketones 78a with lithium ynolates afford /3-lactone lithium enolates 79a, which spontaneously cyclize to give bicyclic compounds 80a. These intermediates, which are stable enough to be isolated, are treated with TsOH under heating to provide substituted furans 81a via decarboxylation and dehydration. Thiophenes (e.g. 81b) are also synthesized by the analogous scheme via intermediate 80b using a-acylthioketones (78b) as a substrate. In the synthesis of pyrroles using a-acylaminoketones as a substrate, the cyclization proceeded at —20 °C, and the -lactone was subsequently ring-opened via /3-elimination to furnish pyrroles in one-pot (equation 35). ... 

Asymmetric cycloadditions of the chiral non-racemic nitrones 101 and 103 afford the isoxazolidinones 102 and 104 respectively, with high diastereoselectivity. This process can lead to an efficient asymmetric synthesis of /3-amino acids (equations 42 and 43) . This is the first example of asymmetric reactions with ynolates. It is noteworthy that the ynolates show higher reactivity and stereoselectivity than the corresponding lithium ester enolates and demonstrate the high potential of lithium ynolates in asymmetric reactions. 

Olefination of acylsilanes is expected to become a useful method for the preparation of vinylsilanes, which are a powerful synthetic tool . Olefination of the acylsilanes 135 with ynolates provides the -silyl-a,/S-unsaturated esters 136 in high yields with high Z-selectivity (equation 56) . In most cases, the E isomers could not be detected by H NMR and HPLC. This is the first general method for the stereoselective synthesis of tetrasubstituted olefins. 

Nucleophilic reactions of lithium thioalkynolates with electrophiles mostly occur at the 3 -position to afford alkynyl sulfides. For example, 3 -silylation and 3 -stannation are shown in equation 80 the synthesis and -alkylation of a quaternary ammonium thioalkynolate are shown in equation 81. Exceptionally, lithium thioalkynolates add to ketones to form -thiolactones, which are converted into alkenes on elimination of carbon oxysulfide (equation 82). Contrary to lithium ynolates, thioalkynolates do not react with aldehydes. ... 

The two parts of the present volume contain seventeen chapters written by experts from eleven countries. They cover computational chemistry, structural chemistry by spectroscopic methods, luminescence, thermochemistry, synthesis, various aspect of chemical behavior such as application as synthons, acid-base properties, coordination chemistry, redox behavior, electrochemistry, analytical chemistry and biological aspects of the metal enolates. Chapters are devoted to special families of compounds, such as the metal ynolates and 1,2-thiolenes and, besides their use as synthons in organic and inorganic chemistry, chapters appear on applications of metal enolates in structural analysis as NMR shift reagents, catalysis, polymerization, electronic devices and deposition of metals and their oxides. 

The anionic inverse electron demand 1,3-dipolar cycloaddition of ynolates with chiral nitrones followed by quenching of the initially generated enolate was applied to the synthesis of 5-isoxazolidinones with high yields and good diastereoselectivity. The primary adducts could also be alkylated to obtain 4,4-disubstituted isoxazolidinones (Scheme 133) <200381441, 2005TA2821>. 

Shindo M, Yoshimura Y, Hayashi M, Soejima H, Yoshikawa T, Matsumoto K, Shishido K (2007) Synthesis of multisubstituted furans, pyrroles, and thiophenes via ynolates. Org Lett 9 1963-1966... 

Homer-Wadsworth-Emmons reactions encounter serious problems of reactivity, stereoselectivity, and generality when used to form tetrasubstituted olefins. Most studies on the synthesis of tetrasubstituted olefins exploit alternative routes based on carbometalation of alkynes [17-19]. However, these processes have difficulties associated with the regioselectivity of the initial carbometalation and with reactivity during the final coupling. Here we describe stereoselective s3mtheses of tetrasubstituted olefins, via the olefination of carbonyl compounds with ynolates, as well as some synthetic applications [20,21]. 

Fig. 9 Synthesis of bongkiekic acid using olefination with ynolate...

This coupling reaction of alkenylgermanes can be applied to the synthesis of estrogen receptor modulator tamoxifen (112), which is used in the clinical treatment of estrogen-dependent breast cancer (Fig. 40). The benzoyl triethylgermane (108) is olefinated with ynolate to give the aUcenylgermane 109, which is coupled... 

Stereoselective synthesis of tetrasubstituted alkenes remains a challenging task. A unique solution to this problem is to use torquoselectivity-controlled oletina-tion of carbonyl compounds with ynolates, which is summarized in Chapter 1. In general, the stereoselective synthesis of Z-alkenes, which are thermodynamically less favorable, is more difficult than the synthesis of corresponding -isomers. In Chapter 2, various methods for stereoselective synthesis of Z-alkenes are reviewed. Finally, the C=C double bond formation through catalytic carbene transformation has recently emerged as a new approach toward olefin synthesis. Two chapters covering olefin synthesis based on catalytic carbene transformations are included (Chapter 5 and Chapter 8). 

Review Shindo M, Mori S. Torquoselective olefination of carbonyl compounds with ynolates highly efficient stereoselective synthesis of tetrasubstituted alkenes. Synlett 2008 2231-2243. 

Kozmin et al. applied enyne metathesis between olefin and silyl ynolate to the synthesis of two isomeric eremo-philanes (190 and 191, Scheme 24.48) isolated from the flowering plants of the Compositae family. RCM of 186 was carried out in the presence of [Ru]-II, and the subsequent treatment with HF gave enone 188. 

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