Lewis acids zinc bromide

This reaction has been extended to a similar alkylation with more reactive primary and secondary alkyl halides, such as benzylic and allylic halides. For this purpose the milder Lewis acid zinc bromide is generally preferable to titanium(IV) chloride as catalyst. ... 

Phenylthioalkylation of silyl enol ethers. Silyl enol ethers of ketones, aldehydes, esters, and lactones can be alkylated regiospecifically by a -chloroalkyl phenyl sulfides in fhe presence of a Lewis acid. Zinc bromide and titanium(IV) chloride are the most effective catalysts. The former is more satisfactory for enol ethers derived from esters and lactongs. ZnBr2 and TiCL are about equally satisfactory for enol ethers of ketones. The combination of TiCL and Ti(0-f-Pr)4 is more satisfactory for enol ethers of aldehydes. Since the products can be desulfurized by Raney nickel, this reaction also provides a method for alkylation of carbonyl compounds. Of more interest, sulfoxide elimination provides a useful route to a,B-unsaturated carbonyl compounds. 

The cyclohexylidene protecting group has been employed in several syntheses. A preparation of 2,3-0-cyclohexylidene-4-deoxy-L-threose (445) fi om L-( + )-diethyltartrate (lb) in seven steps illustrates one synthetic application (Scheme 99). Conversion of the monobenzyl protected alcohol 443 to its tosylate followed by reduction with sodium borohydride provides the deoxy intermediate 444, which is reductively deprotected and Swem oxidized to 445 in good overall yield. Treatment with benzylamine provides an imine that undergoes a stereoselective carbon-carbon bond forming reaction with a-lithio-A, A -dimethylacetamide in the presence of the Lewis acid zinc bromide to furnish, after Cbz-amine protection, the j9-aminoamide 446. This is converted in four steps to A -acetyl-L-daunosamine (447), a sugar moiety particularly important as the carbohydrate constituent of the anthracycline antibiotics [149]. 

E)-a.,fl-Unsaturated acids. Zinc bromide is the most effective Lewis acid for promoting a reaction of C,0,0-tris(trimethylsilyl) ketene acetal (1) with aldehydes (but not ketones) to form a,p-unsaturated acids. The ketene acetal can be prepared as shown in equation (I). 

A very different, but similarly effective, auxiliary is the chiral carbonyl(t/5-cyclopentadienyl)(tri-phenylphosphine)iron moiety. When the z./i-unsaturated acyl-iron complex ( -)-(/ )-11 is treated by a modified Simmons Smith reagent, a 91 9 mixture of cyclopropane diastereomers is isolated in good yield73. Precomplexation of the starting iron complex by the Lewis acid zinc(II) chloride seems to be necessary to obtain good selectivity. The chiral iron moiety can then be removed oxidatively by bromine treatment, and the intermediate acyl bromides converted into amides by reaction with (/ )- -phenylethylamine. 

Technical grade zinc cyanide was used as supplied by Matheson, Coleman and Bell. Other Lewis acids, notably aluminum chloride, zinc bromide, and zinc iodide may be used as catalysts for the reaction. 

Allylsilanes or allylstannanes in the presence of a bidentate Lewis acid such as tin(IV) chloride, titanium(IV) chloride, zinc chloride, and magnesium bromide as well as diallylzinc, are promising choices (Table 1). 

The zinc chloride is acting here as a Lewis acid. Similarly, thiirane dioxides react with metal halides such as lithium and magnesium chlorides, bromides and iodides in ether or THF to give the halo-metal sulfmates (130) in fair yields157. 

For preparative reactions, Lewis acid catalysts are used. Zinc chloride or ferric chloride can be used in chlorination, and metallic iron, which generates ferric bromide, is often used in bromination. The Lewis acid facilitates cleavage of the halogen-halogen bond. 

Chloride ion is a weaker nucleophile than bromide and iodide ions => chloride does not react with 1° or 2° alcohols unless zinc chloride or some Lewis acid is added to the reaction. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

Kinetic studies using the water-soluble nitrile li revealed first-order dependence in both nitrile and azide and one-half order dependence for zinc bromide. The mechanism of the addition of hydrazoic acid/azide ion to a nitrile to give a tetrazole has been debated, with evidence supporting both a two-step mechanism (Scheme 1, eq 2) and a concerted [2 + 3] cycloaddition (Scheme 1, eq 3). Our mechanistic studies to date imply that the role of zinc is not simply that of a Lewis acid a number of other Lewis acids were tested and caused little to no acceleration of the reaction. In contrast, Zn exhibited a 10-fold rate acceleration at 0.03 M, which corresponds to a rate acceleration of approximately 300 at the concentrations typically used. The exact role of zinc is not yet clear. 

One exception is the reaction of acetone oxime with divinyl ketone in the presence of an equimolar amount of zinc(II) bromide (162). Acetone oxime reacts with divinyl ketone on heating in THE at reflux, leading to both conjugate addition and nitrone cycloaddition, producing a 5 1 mixture of regioisomers with 8-oxa-l-azabicyclo[3.2.1]octan-4-one as the major isomer (Scheme 11.42). On the other hand, in the presence of an equimolar amount of zinc(II) bromide, 7-oxa-l-azabicyclo[3.2.1]octan-4-one is the major isomer (97 3) in a total yield of 97%, indicating that the Lewis acid has controlled the regioselectivity of the second step, namely, the cycloaddition. 

Campholenic Aldehyde Manufacture. Campholenic aldehyde is readily obtained by the Lewis-acid-catalyzed rearrangement of a-pinene oxide. It has become an important intermediate for the synthesis of a wide range of sandalwood fragrance compounds. Epoxidation of (+)- Ct-pinene (8) also gives the (+)-o -a-pinene epoxide [1686-14-2] (80) and rearrangement with zinc bromide is highly stereospecific and gives (-)-campholenic aldehyde... 

Notes This alcohol protecting is easily attached and readily removed by Lewis acids such as zinc bromide and titanium tetrachloride. Phenols can be protected (reaction of the sodium salt with MEMC1) and deprotected with TFA. More easily removed than the MOM group. 

Aluminum trichloride is the most commonly used catalyst, although aluminum tribromide is more efficient.1 For the rearrangement of l-broino-2-chloro-1,L2-lrifluoroethane (3) to 2-bromo-2-chloro-l,l,l-trifhioroethane (4). none of the following Lewis acids are effective iron(III) chloride. iron(III) bromide, antimony(III) chloride, antimony(V) chloride. tin(IV) chloride, titanium(IV) chloride, zinc(II) chloride, and boron trifluoride-diethyl ether complex.1" ... 

Chloride ion is a weaker nucleophile than bromide ion because it is smaller and less polarizable. An additional Lewis acid, such as zinc chloride (ZnCl2), is sometimes necessary to promote the reaction of HC1 with primary and secondary alcohols. Zinc chloride coordinates with the oxygen of the alcohol in the same way a proton does— except that zinc chloride coordinates more strongly. 

Most Lewis acids such as zinc bromid in methanol, dichtoroethylalane in di-chloromethane, trifluoroborane etherate and ethane-1,2-dithiol in methanol,372 or iron(lll) chloride373 will also cleave trity ethers. Scheme 4.202 illustrates the use of zinc bromide in dichloromethane374 to remove a trityl ether in the presence of two a Hylic TBS ethers during a synthesis of ACRL toxin 111b.375... 

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