Acetals Lewis acid-mediated

Beecham P-lactamase iiihibitoi BRL 42715 [102209-75-6] (89, R = Na), C IlgN O SNa (105). Lithium diphenylamide, a weaker base, was used to generate the anion of (88) which on sequential treatment with l-methyl-l,2,3-ttia2ole-4-carbaldehyde and acetic anhydride gives a mixture of diastereomers of the bromoacetate (90). Reductive elimination then provided the (Z)-penem (89, R = d5 Q [ OC15 -p) as major product which on Lewis acid mediated deprotection gave BRL 42715 (89, R = Na). 

The Lewis acid mediated addition of silyl enol ethers or silylketcne acetals to oc-alkoxyaldehydcs is the most versatile and reliable method of providing chelation control in aldol-type additions3. The stereochemical outcome is as predicted by Cram s cyclic model11 ... 

Lewis acid-mediated ionization of acetals also generates electrophilic carbon intermediates that react readily with allylic stannanes.190 Dithioacetals can be activated by the sulfonium salt [(CH3)2SSCH3]+BF4,191... 

The thus prepared /l-trifluoromethylated 0,S-acetal 4 allows us to make a carbon-carbon bond via a carbocation at the -position to the CF 3 group as shown in Scheme 6.9 [48]. Interestingly, Lewis acid-mediated allylation and cyanation can be achieved efficiently only when electrogenerated acids (EGA) are employed. 

The product ratio of 8K/9K is similar to that of the Lewis acid-mediated reaction of 4a-c. These products of the C2-C3 bond cleavage (8K and 9K) may be formed via alkylideneallyl cation intermediate, which is formed by the oxygen protonation of 4. Thus, the product ratio of 10/(8K + 9K) is controlled by the protonations at the olefinic carbon and at the acetal oxygen of 4. 

Preparation of (R)-(+)-3-hydroxy-4-methylpentanoic acid has been reported previously by the submitters.5 Alternative syntheses of (R)-(+)- or (S)-(-)-3-hydroxy-4-methylpentanoic acid rely on aidoi reactions of chiral ketone, ester, or amide enolates,2 8 10 and Lewis-acid mediated additions of chiral silyl ketene acetals to Isobutyraldehyde.3 11 Since both enantiomers of HYTRA are readily available this method enables one to prepare (S)-3-hydroxy-4-methylpentanoic acid as well. 

While the perfluorinated acetates do prefer insertion, they are still capable of forming 1,3-dipoles and have demonstrated interesting effects on the regioselectivity of intramolecular cycloaddition reactions, presumably through Lewis acid-mediated effects on the dipolarophile [83]. Other chemoselectivity effects have been noted in the intramolecular cycloaddition reactions and may or may not be partially induced by conformation and sterics [84]. It was further demonstrated thaL when possible, O-H insertion is the predominant outcome over other types of insertion for rhodium]II)-car-benes, independently of the catalyst. However, cycloaddition reactions have been demonstrated to be hgand-dependent [85]. 

Section B of Scheme 9.4 gives some additional examples of Lewis acid-mediated reactions of allylic silanes with aldehydes and acetals. 

Our initial aim was to prepare the epoxyalkyl glycosides 60 as mixtures of dia-stereoisomers. The literature abounds with methods for such syntheses, ranging from Lewis-acid mediated condensations of the acetate 62 [43,44] to acid-catalyzed additions to the oxazoline 63 [45,46]. All of these transformations seemed rather cumbersome and long-winded to us, especially those involving the separate preparation of the oxazoline ... 

Silyl enol ethers of acyl silanes have been used in Lewis acid-mediated Mukaiyama reactions with acetals. Treatment of the resulting /1-alkoxy acyl silanes with tetrabutylammonium hydroxide or tetrabutylammonium fluoride gave the corresponding a,/J-unsaturated aldehydes (Scheme 99)210. 

Fot related Lewis acid mediated rearrangements of cyclic vinyl acetals affording... 

Later on, Schreiber used consecutively these two reactions in the key step for the synthesis of diterpene (-i-)-epoxydictimene (73), starting from natural (R)-pulegone [116,117]. This approach was built on their preliminary studies on Lewis acid mediated intermolecular Nicholas reactions [118]. They prepared functionalized enyne 70 bearing a mixed acetal. This compound was transformed into its dicobalt-hexacarbonyl complex and, in the presence of a carefully selected Lewis acid, it formed a stabilized carbocation by release of the more accessible ethyl moiety. This cation reacted intramolecularly with the allylsilane giving the central eight membered ring of the natural product... 

Lewis acid-mediated ene reaction of di- —)- / ,25)-2-phenyl-1-cyclohexyl diazenedicarboxylate with cyclohexene using tin(IV) chloride in dichloromethane at —60 °C for 5 min afforded the azo-ene adduct in 80% yield after purification by flash chromatography (eq 2). The H NMR spectrum of the azo-ene adduct recorded at 380 K in deuterated toluene established the presence of only one diastereomer. Further analysis of the ene adduct by HPLC on a Whatman Partisil 5 normal phase silica column using hexane-ethyl acetate (9 1) as eluent confirmed the presence of only one diastereomer. 

Protected (5)-ethyl lactate cleanly acylates methyllithium to afford the 2-butanone with essentially complete enantiomeric fidelity and in nearly quantitative yield. Various diastereoselective constructions were achieved by nucleophilic addition to the ketone (eq 5). For example, addition of vinyllithiums, followed by acetal formation and Lewis acid-mediated rearrangement, provided a ready entry into the indicated 3-acyltetrahydrofurans. 

Minehan, T G, Kishi, Y, p-selective C-glycosidations Lewis-acid mediated reactions of carbohydrates with silyl ketene acetals. Tetrahedron Lett., 38, 6815-6818, 1997. 

The pioneering discovery by Mukaiyama in 1974 of the Lewis acid mediated aldol addition reaction of enol silanes and aldehydes paved the way for subsequent explosive development of this innovative method for C-C bond formation. One of the central features of the Mukaiyama aldol process is that the typical enol silane is un-reactive at ambient temperatures with typical aldehydes. This reactivity profile allows exquisite control of the reaction stereoselectivity by various Lewis acids additionally, it has led to the advances in catalytic, enantioselective aldol methodology. Recent observations involving novel enol silanes, such as enoxy silacyclobutanes and O-si-lyl M(9-ketene acetals have expanded the scope of this process and provided additional insight into the mechanistic manifolds available to this versatile reaction. 

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