Lewis-acid-promoted alkylations

Lewis-acid-promoted alkylations of silylenol ethers and silyl ketene acetals [195] with Co-complexed acetylenic acetals [196] and acetylenic aldehydes [197,198] (Scheme 4-56) also proceed with fair to excellent syn diastereoselectivity, in contrast to the low selectivity reactions of the free acetylenic derivatives [199, 200]. Reactions of the complexed aldehydes with lithium enolates are stereospecific, with (Z)-enolates giving syn selectivity and ( )-enolates anti selectivity [201]. The complementary stereoselectivity of the crossed aldol reactions of free and cobalt-complexed propynals with silyl ketene 0,S-acetals has been elaborated by Hanoaka exclusive syn selectivity is exhibited by the complexes and high anti selectivity is found with pro-... 

The following two examples from our recent work also illustrate the limitations of our systematic approach to Lewis acid promoted alkylations of aliphatic tt systems. The reaction of cumyl chloride 26 with tetramethyl-ethylene in presence of various Lewis acids gave complex mixtures of products, probably because of the strain generated during the formation of the regular addition product. Titanium tetrachloride, however, induces a rapid consecutive cyclization, and the TiCl catalyzed reaction of 26 with tetramethylethylene yields hexamethylindan in 72% yield. Since the aromatic ring can be oxidized under Ru(VIII) catalysis, the reaction sequence shown in Figure 16 allows the construction of acyclic compounds with adjacent quaternary carbon atoms. 

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. 

Reaction with 2,3-epoxy alcohols. Both (CH3)2CuLi and (CH3)2CuCNLi2 react with trans-2,3-epoxy alcohols (with a simple alkyl group at C4) in ether to give about 1 1 mixtures of 1,2- and 1,3-diols. Addition of TMEDA or an imida-zolidinone (DMI, 11, 202) promotes reaction at C2 to give 1,3-diols, whereas addition of a Lewis acid promotes reaction at C3 to give 1,2-diols. 

In a review on the addition of carbenium ions to alkenes (equation 19) as a general procedure for carbon-carbon bond formation50, Mayr reported on investigations which also include the reactions of a variety of 1,3-dienes toward electrophilic carbon species generated by Lewis acid-promoted heterolysis of alkyl chlorides. 

The combination of a metal phenoxide and a Lewis acid facilitates alkylation of the phenolic moiety by 1,1,3,3-tetramethoxypropane and promotes specific ortho attack. Spontaneous cyclization leads to a mixture of two stereoisomers of 2,4-diethoxychroman (81JHC1325). 

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. 

The important commercial compound (/ )-pantolactone is formed in high yield and ee from the bis-carbamate 417 after carboxylation and lactonisation.178 Attempts to quench the organolithium with Me3SiCl failed instead the silyl chloride acted as a Lewis acid, promoting displacement of the second carbamate and leading to the cyclopropane 420.162>179 Further functionalisation of the cyclopropane was possible by stereospecific alkylation of the ring. 

Allylsilanes are available for Lewis acid-promoted allylation of reactive alkyl electrophiles such as allyl halides and esters. 6 Recently, much attention has been focused on catalytic allylation of alkyl esters, ethers, and alcohols with allylsilanes.217-221... 

Protected 1,3-an/i-diols 14 are accessible by the highly stereoselective Lewis acid promoted addition of dialkylzinc compounds to 4-acet-oxy-1,3-dioxanes 13 (Scheme 3) [5]. The two d, -orientated alkyl substituents at C2 and C6 fix the carboxonium ion 15 in the half-chair conformation, which undergoes preferential axial attack by the dialkylzinc under stereoelec-tronic control. The 4-acetoxy-1,3-dioxanes 13 may be synthesized from the Seebach 1,3-diox-an-4-ones 12 by reduction with diisobutylalumi-num hydride (DIBAH) and acetylation. Since dialkylzinc compounds are now readily available and are compatible with many functional groups, this... 

Scheme 10 Chem selectivity control in Lewis acid promoted reactions of alkyl halides with alkenes.

A large part of the discussions in this chapter was concerned with carbo-cationic [1 l]-telomerizations, i.e., Lewis acid-promoted additions of alkyl halides and related compounds to CC-double bonds with formation of 1 1 products. The relevance of these studies for the initiation of carbo-cationic polymerizations, as described in Scheme 9 (Section III.A), is obvious. 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

Scheme 3.35. Tetrahydrofurar synthesis by means of MOM a-alkoxy alkyl cuprate conjugate additions followed by Lewis acid-promoted cyclization (MOM = methoxymethyl) [129].

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