Ketones Lewis acid promotion

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. 

The conversion of anomerically linked enol ethers 29 into either the cis- or trans-substituted pyranyl ketones with high diastereoselectivity and yield involves a Lewis acid-promoted O —> C rearrangement (Scheme 19) <00JCS(P1)2385>. Under similar conditions, homoallylic ethers 30 ring open and the oxonium ions then recyclise to new pyran derivatives 31. Whilst the product is a mixture of alkene isomers, catalytic hydrogenation occurs with excellent diastereoselectivity (Scheme 20) <00JCS(P1)1829>. 

We have just seen in a preceding scheme (see Section 4.2.1.5) an example of alkylation of a silylated enolate with phenylthiomethyl chloride. The Lewis acid-promoted phenylthioalkylation of O-silylated enolates of ketones, aldehydes, esters and lactones has been used by Paterson and Fleming as a convenient synthetic route to a-alkylated or alkylidenated carbonyl compounds [323-325] according to the accompanying scheme. 

Broensted or Lewis acids promote heterolysis of the C-O bond and formation of a peroxy allylic or benzylic cation which can collapse to dioxetane [52d] or be trapped by aldehydes or ketones [100] to form... 

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

Representative examples are summarized in Table 7. Aliphatic and aromatic aldehydes as well as ketones could be used (entries 1-5). a,/ -Unsaturated substrates gave predominantly or exclusively 1,4-addition compounds (entries 6 and 7). Under the Lewis acid-promoted conditions, toluene was found to be a more effective solvent than THF. 

An interesting double ring expansion sequence developed by Vogel involves the initial pinacol coupling of cyclobutanone, isomerization to ketone 79 in acid, followed by reduction and Lewis acid-promoted Wagner-Meerwein rearrangement with dehydration (Scheme 19).129) For preparative purposes, 80 can be more... 

The Lewis acid promoted addition of allylsilane (48) to nitroalkoie (47) gave the unsaturated ketone... 

In this synthesis of 1,5-dicaibonyl compounds, 3-butenyl halide is behaving as a madced 3-oxobutyl reagent, and can be used as an equivalent of metiiyl vinyl ketone. These reactirais offer new anellation methods. Also 1,4-addition of the allyl group to enones, followed by oxidatitm. offers a conveiuent synthetic method for 1,5-diketone preparation. Lewis acid promoted Nfichael addition of allylsilane (48) to a,p-unsaturated ketones, followed by the palladium-catalyzed oxidation, affods 1,5-diketones (Scheme 17). 3... 

The Lewis acid promoted addition of allylsilane (48) to nitroalkene (47) gave the unsaturated ketone (49) after hydrolysis of the nitro group. The palladium-catalyzed oxidation affords the 1,4-diketone (50 Scheme 13). °... 

It is the structural variety of the precursors which lends versatility to the Nazarov cyclization and which also serves as the organizational framework for this chapter. To facilitate presentation die reaction is divided into five categories (i) (Lewis) acid-promoted and photochemical cyclization of divinyl and allyl vinyl ketones (ii) silicon- and tin-directed Nazarov cyclizations of divinyl ketones (iii) in situ generation/cyclization of divinyl ketones (iv) solvolysis to produce divinyl ketone equivalents (v) coupling reactions to form and cyclize divinyl ketones. The logic of this sequence follows from the order of decreasing structural similarity of the precursors to divinyl ketones. The last three subgroups encompass considerable structural diversity which will be discussed in each section. 

The first studies on Lewis acid promotion of allylic stannane additions were conducted with BF3 OEt2 (Table 4) [13]. Aldehydes were found to be more reactive than ketones and methyl ketones were more reactive than internal ketones. Addition to 4-fert-butylcyclohexanone favored equatorial allylation by 85 15. 

Equation 54 describes the preparation of dienes by a similar cyclopropane cleavage followed by proton transfer and elimination of sulfinate. The weak donor ability of a (trimethylsilyl)methyl group also assists Lewis acid-promoted ring cleavage according to equation 55, which allows synthesis of y, -unsaturated ketones Interestingly, the related ester opens smoothly only if fluoride reagents are employed (equation 56) ... 

LEWIS ACID promoted REACTIONS OF ALDEHYDES AND KETONES... 

Acetals prepared from chiral diols and carbonyl compounds serve as a chiral synthetic equivalent of aldehydes or ketones. 1,3-Dioxanes synthesized from chiral 2,4-pentanediols are especially useful, and high asymmetric inductions are observed in the Lewis acid promoted reactions of a variety of organometallic compounds. After the removal of the chiral auxiliary by the oxidation and -elimination procedures, optically active alcohols are obtained. Optically active propargylic alcohols and cyanohydrins are synthesized from organosilane compounds, TMS-C CR or TMS-CN in the presence of TiCU (Scheme 24). 1 6-138 Reactive wganometals such as alkyl-lithiums, -magnesiums or -coppers also react with chiral... 

Compared with aldehydes and ketones, aldimines and ketimines are less reactive towards nucleophilic addition. Furthermore, imine additions are subject to steric constraints, and rapid deprotonation proceeds with imines bearing ot-hydrogen atoms. The Lewis acid promoted addition methodology has provided a solution to these problems. 

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