Carbonyl compounds Lewis acid catalyzed

For the reaction of carbonyl compounds with conjugated dienes two mechanistic pathways have generally been taken into account when Lewis acid-catalyzed reactions are considered ... 

There have been few mechanistic studies of Lewis acid-catalyzed cycloaddition reactions with carbonyl compounds. Danishefsky et ah, for example, concluded that the reaction of benzaldehyde 1 with trans-l-methoxy-3-(trimethylsilyloxy)-l,3-di-methyl-1,3-butadiene (Danishefsky s diene) 2 in the presence of BF3 as the catalyst proceeds via a stepwise mechanism, whereas a concerted reaction occurs when ZnCl2 or lanthanides are used as catalysts (Scheme 4.3) [7]. The evidence of a change in the diastereochemistry of the reaction is that trans-3 is the major cycloaddition product in the Bp3-catalyzed reaction, whereas cis-3 is the major product in, for example, the ZnCl2-catalyzed reaction - the latter resulting from exo addition (Scheme 4.3). 

The Lewis acid-catalyzed 1,3-dipolar cycloaddition reaction of nitrones to a,/ -un-saturated carbonyl compound in the presence of Lewis acids has been investigated by Tanaka et al. [31]. Ab-initio calculations were performed in a model reaction of the simple nitrone 18 reacting with acrolein 1 to give the two cycloadducts 19 and 20 (Scheme 8.7). 

Essentially all allylsilanes (M = SiR3, Section D.l.3.3.3.5.) with the exception of fluorosil-iconates11 and most of the trialkyl(allyl)stannancs (Section D.l. 3.3.3.6.), which have only very weak Lewis acidic properties, require a strong Lewis acid to trigger the reaction with a carbonyl compound by the preceding formation of an x-oxycarbenium ion, which attacks the allylic compound in an ionic open-chain pathway. These Lewis acid catalyzed carbonyl additions offer new possibilities for the control of the simple and induced diastereoselectivity12. 

Lewis acid catalyzed carbonyl addition of allylsilanes (Section D.l.3.3.3.5.) and allylstannanes (Section D.l.3.3.3.6.) usually proceed with clean allylic inversion (Section D.l.3.3.1.2.). Since these compounds are prepared by several routes and are also stable enough to be purified, each regioisomer can be approached. 

Lewis-acid-catalyzed cycloadditions of dienophiles, such as a,/l-unsaturated carbonyl compounds, with open-chain carbon-dienes, are generally highly ortho-para regioselective because the oxygen complexation increases the difference of LUMO coefficients of the alkene moiety. 

Lewis-acid catalyzed inverse electron-demand Diels-Alder reactions between conjugated carbonyl compounds and simple alkenes and enolethers also allow dihydropyranes to be prepared. SnCU-Catalyzed cycloaddition of... 

Trimethylsilyl triflate (McsSiOTf) acts as an even stronger Lewis acid than Sc(OTf)3 in the photoinduced electron-transfer reactions of AcrCO in dichloro-methane. In general, such enhancement of the redox reactivity of the Lewis acid complexes leads to the efficient C—C bond formation between organosilanes and aromatic carbonyl compounds via the Lewis-acid-catalyzed photoinduced electron transfer. Formation of the radical ion pair in photoinduced electron transfer from PhCHiSiMes to the (l-NA) -Mg(C104)2 complex (Scheme 11) and the AcrCO -Sc(OTf)3 complex (Scheme 12) was confirmed by the laser flash experiments [113]. 

Scheme 9.6 gives some other examples of Lewis acid-catalyzed reactions of allylic stannanes with carbonyl compounds. 

Several methods for the anti-selective, asymmetric aldol reaction recorded in the literature include (i) the use of boron, titanium, or tin(ll) enolate carrying chiral ligands, (ii) Lewis acid-catalyzed aldol reactions of a metal enolate of chiral carbonyl compounds, and (iii) the use of the metal enolate derived from a chiral carbonyl compound. Although many of these methods provide anti-aldols with high enantioselectivities, these methods are not as convenient or widely applicable as the method reported here, because of problems associated with the availability of reagents, the generality of reactions, or the required reaction conditions. 

Lewis acid-catalyzed inter- or intramolecular condensation of carbonyl compounds with strained cyclic peroxides represents one of the most general and useful methods... 

A formal asymmetric nucleophilic addition to carbonyl compounds is achieved by Trost and his co-workers in the allylic alkylation of acylals of alkenals. An excellent enantioselectivity is observed in this alkylation. The starting acylals are easily prepared by the Lewis-acid catalyzed addition of acid anhydrides to aldehydes, by use of Trost s ligand 118 (Scheme 13), where various carbon-centered nucleophiles are available (Scheme l4),101,101a-10lc Asymmetric synthesis of some natural products is achieved according to this procedure. 

Lewis acids catalyze electrophilic reactions of carbonyl compounds with phenols. Reaction of ethyl pyruvate and 1-naphthol in the presence of a dibomacyclopentadienyl Zr(IV) complex affords the ortho-hy-dtoxyalkylated product in up to 87% ee (Scheme 121). Intervention of a Zr naphthoxide intermediate has been proposed, and addition of a small amount of water increases the enantioselectivity (293). 

It has been long established that Lewis acid-catalysed [2+2] cycloaddition of ketenes and carbonyl compounds provides access to 2-oxetanones. In the development of this reaction prior to 1996, there has been a specific focus on controlling the stereochemistry of the /3-lactone product and cycloadditions have been achieved between trimethyl-silylketene and aldehydes with up to 90% stereoselectivity, as discussed in CHEC-II(1996) <1996CHEC-II(1)721>. CHEC(1984) and CHEC-II(1996) also discuss examples of the Lewis acid-catalyzed, nonphotolytic [2+2] cycloaddition of electron-rich alkenes with aldehydes or ketones <1984CHEC(7)363, 1996GHEC-II(1)721>. While this method can have some advantages over the photolytic reaction in terms of regioselectivity, no examples of this reaction have been reported in recent years. 

The reaction of -halo carbonyl compounds with primary amides is appropriate for oxazoles containing one or more aryl groups . Ureas form 2-aminooxazoles. Formamide can be used resulting in a free 2-position in the oxazole. A convenient synthesis of 5-substituted-4-cyanooxazoles 223 is based on the condensation of -hydroxy—cyanoenamines 222 with trimethyl orthoformate (Scheme 109). The cyanoenamine intermediates 222 are derived from Lewis acid-catalyzed Passerini reactions between /-butyl isonitrile and aldehydes <2002S1969>. 

Lewis acid-catalyzed cyclization of carbonyl compounds 393 or 395 with AICI3 gives benzothiophene 394 <2001HC0271> or thioindoxyl 396 <2001JOC2966>, respectively. ZnCl2-mediated cyclization of 397 affords thienothiophene 398 <2001J(P1)2483>. 

U nder thermal or Lewis acid catalyzed conditions, reactions of fluoroalkyl carbonyl compounds with alkenes usually provide the ene adduct. " One example of a [2 + 2] cycloaddition between hexafluoroacetone and an alkyne has been reported. ... 

ZnCh catalyzed ene reaction of methyl vinyl ketone and acrolein with p-pinene in ether at 25 C gives the expected ene adducts in 62% and 32% yields, respectively. Methyl vinyl ketone is reported to undergo AICI3 catalyzed ene reactions with limonene, carvone and perillaldehyde. Although Lewis acid catalyzed ene reactions of acrolein and methyl vinyl ketone with alkenes are probably general, the initial products often cannot be isolated since the unsaturated carbonyl compound undergoes an intramolecular Lewis acid catalyzed type II ene reaction. ... 

Reaction of alkenes with carbonyl compounds or carbonyl derivatives in the presence of Lewis acids, the ene reaction, enables the stereoselective preparation of highly functionalized compounds. Copper Lewis acids activate both aldehydes and imines in ene reactions. Evans has reported that Cu(II) Lewis acids catalyze glyoxylates in reactions with alkenes (Sch. 56) [103]. The homoallylic alcohols 257 and 259 are produced in high yield and enantioselectivity. The bis aquo complex 260 is a readily prepared and air-stable catalyst and gave high chemical yield and excellent selectivity in the ene reactions. Another point of note is that catalysts 260 and 261 furnish enantiomeric products even though they differ from each other only by the substituent at the 4-posi-tion of the oxazoline. 

Silylated cyanohydrins have found considerable utility in the regioselective protection of p-qui-nones, as intermediates for the preparation of 3-amino alcohols and as precursors to acyl anion equivalents. Such compounds are typicdly prepared in high yield by either thermal or Lewis acid catalyzed addition of TMS-CN across the carbonyl group. This cyanosilylation has a variety of disadvantages and modified one-pot cyanosilylation procedures have been reported. - The carbonyl group can be regenerated by treatment with acid, silver fluoride or triethylaluminum hydrofluoride followed by base. ... 

In analogy to the preparation of iminium salts, thiocarbenium ions (115) can be created by treatment of carbonyl compounds (1) with thiols," by alkylating (or Lewis acid catalyzed) cleavage of dithioace-tals U14) or by protonation of vinyl sulfides (thio enol ethers) (116 Scheme 55)." ... 

There are two different modes of cyclizations in hetero [4+2] cycloadditions involving Danishefsky s diene 1) concerted (pericyclic) and 2) stepwise. When carbonyl compounds are reacted with Danishefsky s diene, the stepwise pathway is often referred to as the Mukaiyama aldol reaction pathway. The concerted process is called the Diels-Alder pathway. The mode of cyclization in the case of Lewis acid catalyzed reactions depends on the Lewis acid itself and whether it is present in stoichiometric or catalytic amounts. The Mukaiyama aldol pathway has been... 

Mueller, E., Zeeh, B. Lewis acid-catalyzed reaction of carbonyl compounds with tertbutyl isonitrile. Liebigs Ann. Chem. 1966, 696, 72-80. 

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