Lewis acids promoters

Lewis acid promoted condensation of silyl ketene acetals (ester enolate equiv.) with aldehydes proceeds via "open" transition state to give anti aldols starting from either E- or Z- enolates. 

Mukaiyarna-Johnson AJdoJ- Lewis acid promoted condensation of silyl enol ethers with acetals ... 

The selective addition of the second HCN to provide ADN requires the concurrent isomerisation of 3PN to 4-pentenenitrile [592-51 -8] 4PN (eq. 5), and HCN addition to 4PN (eq. 6). A Lewis acid promoter is added to control selectivity and increase rate in these latter steps. Temperatures in the second addition are significandy lower and practical rates may be achieved above 20°C at atmospheric pressure. A key to the success of this homogeneous catalytic process is the abiUty to recover the nickel catalyst from product mixture by extraction with a hydrocarbon solvent. 2-Methylglutaronitrile [4553-62-2] MGN, ethylsuccinonitfile [17611-82-4] ESN, and 2-pentenenitrile [25899-50-7] 2PN, are by-products of this process and are separated from adiponitrile by distillation. 

The HCFC-225 isomers designed to replace CFC-113 are manufactured by Lewis acid promoted addition of HCFC-21 to tetrafluoroethylene... 

Ketene acetals prepared from fluorinated esters by trimethylsilylation undergo Lewis acid-promoted aldol condensations giving satisfactory yields but low diastereoselectivity [27] (equation 22). 

Lewis acids promote migration of fluorine m halofluoroalkenes to yield isomers, which can be transformed easily into perfluorinated alkynes [27. 22] (equation 6)... 

However, Dondoni improved the synthesis by using Yb(OTf)3 as the Lewis acid promoter in THE at reflux to deliver 62 in 95% yield/ ... 

Sdieire 3.3S. Tetrahydrofcifar cyrthecic by mearc of MOM a-allco 7allcylciipfate conjugate additionc followed by Lewie acid-promoted oyclization (MOM = metho rymethyl) [129]. 

The synthesis of f-i-i-crotanecine is accomplished in 10 steps in a 10.2% overall yield, as shown in Scheme 8.42. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter [4-i-2 /intra [3-i-2 cycbaddidon between a ffumaroyloxyxiitroalkene and chiral fi-silylvinyl ether, in which the snbsdtuted silanes are used as hydroxy synthons. ... 

Closely related to the polyepoxide cascade procedure for the synthesis of polycyclic systems is Corey s biomimetic-type, nonenzymatic, oxirane-initiated (Lewis acid-promoted) cation-olefin polyannulation. By this strategy, compound 96, containing the tetracyclic core of scalarenedial, was constructed by exposure of the acyclic epoxy triene precursor 95 to MeAlCl2-promoted cyclization reaction conditions (Scheme 8.25) [45]. 

An excess of Grignard reagent (4 equivalents) or the addition of strong Lewis acids promotes the preference for chelation-controlled. vvn-products (Table 20)22 21 u. In addition, the use of diethyl ether or dichloromethane instead of tetrahydrofuran improves the yield of the chelation-derived syn-product24. 

The diastereofacial selectivity of Lewis acid promoted reactions of allylsilancs with chiral aldehydes has been thoroughly investigated58. Aldehydes with alkyl substituted a-stereogenic centers react with a mild preference for the formation of Cram products, this preference being enhanced by the use of boron trifluoride-diethyl ether complex as catalyst58. 

An interesting and stereoselective synthesis of 1,3-diols has been developed which is based on Lewis acid promoted reactions of /f-(2-propenylsilyloxy (aldehydes. Using titanium(IV) chloride intramolecular allyl transfer takes place to give predominantly Ag/r-l,3-diols, whereas anti-1,3-diols, formed via an / / /-molecular process, are obtained using tin(IV) chloride or boron trifluoride diethyl ether complex71. 

Lewis acids, particularly the boron trifluroride diethyl ether complex, are used to promote the reaction between allyl(trialkyl)- and allyl(triaryl)stannanes and aldehydes and ketones52-54. The mechanism of these Lewis acid promoted reactions may involve coordination of the Lewis acid to the carbonyl compound so increasing its reactivity towards nucleophilic attack, or in situ transmetalation of the allyl(trialkyl)stannane by the Lewis acid to generate a more reactive allylmetal reagent. Which pathway operates in any particular case depends on the order of mixing of the reagents, the Lewis acid, temperature, solvent etc.55- 58. 

The stereoselectivity of Lewis acid promoted reactions between 2-butenylstannanes and aldehydes has been widely studied, and several very useful procedures for stereoselective synthesis have been developed. In particular syn-products are formed stereoselectively in reactions between trialkyl- and triaryl(2-butenyl)stannanes, and aldehydes induced by boron trifluoride-diethyl ether complex, irrespective of the stannane geometry66. 

Therefore, in order to obtain a 1,4-addition of an allyl residue to an enone, two activation modes can be used reactions take place either under electrophilic conditions with Lewis acid promotion, or in the presence of fluoride ions. This is important as the stereochemical outcome often depends on the activation mode selected. 

More recently, the Lewis acid promoted asymmetric 1,4-addition of trimethyl(2-propenyl)silane to chiral a,/ -unsaturated /V-acylamides has been published33. Lewis acid mediated reactions of trimethyl(2-propenyl)silanes with a,/I-unsatu rated AT-acyloxazolidinones or iV-enoylsultams show high chemical yield with good diastereomeric excess. The absolute configuration of the new asymmetric center is controlled by the nature of the Lewis acid used. 

G. Majetich, K. Hull, D. Lowery, C. Ringold,. 1. Defauw in Selectivities in Lewis Acid-Promoted Reactions, D. Schinzer, Ed., Kluwer, Dordrecht 1989. 

The ene reaction of fuUerene (C o) with 3-methylene-2,3-dihydrofuran gives an easily isolated addition product in good yield <96JOC2559>. There is a continuous need for chiral acrylate esters for asymmetric Diels-Alder reactions with high diastereoselectivity. Lewis acid promoted Diels-Alder reactions of acrylate esters from monobenzylated isosorbide 28 (or isomannide) and cyclopentadiene provided exclusively e db-adducts with good yields and high diastereoselectivity <96TL7023>. 

The Lewis acid promoted reactions of styrene with 7V-phenylsulfonyl-l,4-benzoquinone monoimine to the 2-aryIbenzofuranoid ring system have been reported previously. This offers a new route to henzofinanoid neoUgnans (( )-hcarin B, eupomatenoid-1, eupomatenoid-12) (Scheme 25, <96TL6969>). 

Our group has exploited 4-phenylthio-l,3-dioxanes as convenient precursors to 4-lithio-l,3-dioxanes [45,65-69]. 4-Phenylthio-l,3-dioxanes 184 were originally prepared from -silyloxy aldehydes 183 [65] (Eq. 28). Lewis acid-promoted addition of phenylthiotrimethylsilane gave an unstable thioacetal intermediate, which could be converted in situ to the corresponding 1,3-dioxane. Yields for this process are variable, as the product is unstable under the conditions of its formation. The reaction slowly evolves to a mixture of the desired product, the phenylthio acetal of 183, the phenylthio acetal of acetone, and a variety of other unidentified products. 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

Bu2Sn(03SCF3)2.68 The Lewis acids promote ionization of the acetal to an oxonium ion that acts as the electrophile. The products are (J-alkoxy ketones. 

P-Hydroxyketones are also subject to fragmentation. Lewis acids promote fragmentation of mixed aldol products derived from aromatic aldehydes.100... 

Scheme 3.33. Lewis acid-promoted free radical domino cyclization reaction and enantioselective approach.

Denmark and coworkers have found that methylaluminum bis (2,6-di-tert-butyl-4-methyl-phenoxide) (MAD) or methylaluminum bis(2,6-diphenylphenoxide) (MAPh) is effective as the Lewis acid promoter for cycloaddition of 2,2-disubstituted 1-nitroalkenes (Eq. 8.100).158 Other Lewis acids such as SnCl4, TiCl4, and TiCl2(Oi-Pr)2 fail to promote the cycloaddition of 2,2-disubstituted 1-nitroalkenes. The products are converted into 3,3-disubstituted pyrrolidines via hydrogenolysis.158 Reductive cleavage of N-0 bonds produces oxime hemiacetals, which are further reduced to amido aldehydes and finally to pyrrolidines. This reaction provides a useful synthetic method for pyrrolidines, which is discussed later. 

The strategy based on tandem cycloaddition leads to a short and efficient asymmetric synthesis of the pyrrolizidine necine base (-)-hastanecine, as shown in Scheme 8.32.163 Pyrrolizidine alkaloids have a long history for attracting the interest of synthetic chemists because of their physiological properties. The method of Denmark shown in this scheme is very simple and applied to synthesis of various alkaloids. The Lewis acid-promoted [4+2] cycloaddition between 2-acyloxy nitroalkene and chiral vinyl ether gives a nitronate that... 

The simplest nitroalkene, nitroethene, undergoes Lewis acid-promoted [4+2] cycloaddition with chiral vinyl ethers to give cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates react with deficient alkenes to effect a face-selective [3+2] cycloaddition. A remote acetal center controls the stereochemistry of [3+2] cycloaddition. This strategy is applied to synthesis of the pyrrolizidine alkaloids (+)-macronecine and (+)-petasinecine (Scheme 8.33).165... 

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