Zinc chloride enolates

Excellent /(-methyl selectivity is observed in the zinc chloride mediated condensation with 0-silyl enol ethers of 2-pyridinylmethyl thiopropionates109. Supposedly, chelate formation of zinc(II) with the sulfur and the nitrogen atom of the pyridinylmethyl thioester is essential for the high /(-selectivity. The geometry of the ketene acetal also seems to have some influence. 

In the presence of zinc chloride, stereoselective aldol reactions can be carried out. The aldol reaction with the lithium enolate of /-butyl malonate and various a-alkoxy aldehydes gave anti-l,2-diols in high yields, and 2-trityloxypropanal yielded the syn-l,2-diol under the same conditions.633 Stoichiometric amounts of zinc chloride contribute to the formation of aminoni-tropyridines by direct amination of nitropyridines with methoxyamine under basic conditions.634 Zinc chloride can also be used as a radical initiator.635... 

The 1,4-reduction of a,/3-unsaturated aldehydes is best carried out with diphenylsilane in the presence of zinc chloride and tetrakis(triphenylphosphine) palladium436 or a combination of triethylsilane and tris(triphenylphosphine) chlororhodium 437 Other practical approaches use phenylsilane with nickel (0) and triphenylphosphine438 and diphenylsilane with cesium fluoride.83 It is possible to isolate the initial silyl enol ether intermediate from the 1,4-hydrosilylation of o, /3-unsaturated aldehydes (Eq. 264).73,411 The silyl enol ethers are produced as a mixture of E and Z isomers. 

Hypothesis (A) is in contradiction with the experimental evidence, since glycolaldehyde andl, 3-dihydroxy-2-propanone (dihydroxyacetone)9 16 react in the same way as do the sugars. It is evident that these compounds do not possess two contiguous hydroxyl groups. Moreover, when methyl trans-0-(/3-D-glucopyranosyl)acetoacetate enol (LXIV) was treated with zinc chloride under the conditions used by West and by Garda Gonzalez, a... 

Directed Aldol Condensations with Preformed Lithium Enolates in the Presence of Zinc Chloride... 

Hsung and co-workers described the first epoxidation of 1-amidoallenes leading to highly reactive intermediate 292 (Scheme 8.76) [159]. Formation of bicyclic products 291 occurs via iminium enolate 293, which was trapped by cyclopentadiene 290 (X = CH2) or furan 290 (X = 0). [4+3] Cycloaddition of the intermediate 293furnished 291 in good yield as a mixture of mdo-diastereoisomers (-75 25). The best dia-stereoselectivity was found when the reaction was performed in the presence of 2 equiv. of zinc chloride (>96 4). 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

After discovery of the higher stereoselectivities made possible by the zinc chloride catalysis, the synthesis was applied to several secondary alcohols having two or more stereocenters15. The first of these (35,4S)-4-methyl-3-heptanol, was first made with (S)-pinanediol as the chiral director, but has since been made more stereoselectively with (R,R)-2,5-dimethyl-3,4-hexanedi-ol (Section 1.1,2.1.2.1.). Another insect pheromone, eldanolide, requires the use of (R)-pinane-diol in order to obtain the natural enantiomer, and introduces the use of an enolate as well as an allylic Grignard reagent for C-C bond formation15. 

Chloro-l,3-dithiane (797) has been employed as a formyl cation equivalent . The morpholine enamines of a variety of aldehydes and ketones were shown to react with this dithiane to produce the a-(l,3-dithan-2-yl) aldehydes and ketones (798) in good yield (Scheme 186) (77TL2077). In direct analogy with this work, the reaction of enol silyl ethers with 2-ethoxy-l,3-dithiolane in the presence of zinc chloride has been reported to afford half-protected 1,3-dicarbonyl compounds (81TL3243). 

Organoaluminum reagents, 202 1,1,1-Trifluoroacetone, 323 Trityllithium, 338 Zinc chloride, 349 Stereoselective aldol reactions With boron enolates Boron trichloride, 43 Chlorodimethoxyborane, 73 9-(Phenylseleno)-9-borabicyclo-[3.3.1]nonane, 245 With silyl enol ethers... 

Diketones.1 Trimethylsilyl enol ethers are C-acylated by acid chlorides in the presence of zinc chloride or antimony(III) chloride. No other Lewis acids are useful. The reaction provides a convenient route to 1,3-diketones in good to excellent yield. Addition of diethyl ether before quenching of the reaction catalyzed by ZnCl2 improves the yield but has no effect on the SbCl3-promoted reaction. 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

Moreover, removal of ether under vacuum and addition of tetrahydrofuran to the crude mixture of tosylates 229 and LiCl effected the ring expansion to cyclobutanones 230 and cyclobutenyl ethers 231. Upon treatment with anhydrous zinc bromide in methylene chloride, enol ethers 231 also underwent cleavage to give the expected cyclobutanones 230. In this way 2-alkynylcyclobutanones 230 with different substituents on the triple bond (i.e., R = CH3, C6H5, cyclopropyl, etc.) were obtained in 55-60% yield 110). It was obvious from these experiments that LiCl in THF was effective to cleave the MEM ethers 228, while MEM ethers usually require zinc-bromide 103-104), and induce their ring expansion. This likely involves, after ionization of the tosylates in THF, the intermediacy of the cyclobutyl cyclopropylcarbinyl carbenium ion system 232 U0). 

Treatment of chiral, nonracemic vinyl sulfoxides (214) with O-silylated ketene acetal (215) in the presence of a catalytic amount of zinc chloride resulted in an enantioselective additive Pummerer-type reaction, affording the corresponding enantiomerically enriched methyl-4-siloxy-4-sulfenylbuyrate (216) (Scheme 55).122 This is the overall addition of the enolate equivalent to the vinyl sulfoxide. 

Cyclocondensation reactions between 1,2-diaza-l,3-butadienes with silyl enol ethers, mediated by zinc chloride and then TFA, led the to the production of 1 -aminopyrroles <07ASC907>. Extensions of this methodology allowed for the preparation of additional 1-aminopyrroles from bis(silyl enol ethers) <07SL2965> and enamines <07T 11055>. 

Disubstituted furans are available from a,/3-unsaturated enones in a two-step sequence. At first, conjugate addition of a cuprate generates an enolate, which undergoes an aldol reaction with (tetrahydropyranyloxy)acetalde-hyde under zinc chloride catalysis (Scheme 19) <20000 L4095>. Treatment of the reaction product with acid affords the disuhstituted furans in good yields. 

The preparation and reactions of alkylzinc enolates have been studied. The main methods for their synthesis are metal exchange between hthium enolates and zinc chloride, deprotonations of carbonyl compounds with... 

The newest techniques employ silylation. Even the anions of saturated butenolides afford the enol ester on reaction with chlorotrimethylsilane91 applied to a butenolide the method readily supplies a 2-silyloxyfuran. Such ethers are even more easily procured by allowing a butenolide to react with chlorotrimethylsilane in the presence of triethylamine and zinc chloride but for reasons that remain unclear, acetonitrile is the only satisfactory solvent.92 A typical transformation of 2-trimethylsilyloxyfuran is shown in Scheme 19. 

Thiele reaction. In a typical Thiele reaction,45 1,4-benzoquinone (1) is added with stirring at room temperature or below to a solution of a catalyst such as concentrated sulfuric acid in acetic anhydride 1,4-addition to (2) is followed rapidly by enolization (3) and acetylation to give 1,2,4-triacetoxybenzene (4) in high yield. In a few cases Thiele used zinc chloride as catalyst but without apparent advantage. Boron trifluoride etherate would appear to be a more satisfactory Lewis acid since... 

Nickel metal catalysts give mixtures of the corresponding silyl ether and silyl enol ether. The former is produced via hydrosilylation, while the latter is produced via de-hydrogenative silylation. The reaction catalyzed by zinc chloride proceeds under drastic conditions, and the product of aldehydes disproportionates. The reaction of a,jS-unsatu-rated carbonyl compounds with H2PtCl6 proceeds by 1,4-addition, while coupling is also observed on using metallic Ni as catalyst. ... 

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