Reetz alkylation

Three reactions, which were known from the literature to be catalyzed by Lewis acids were selected as test reactions. A, was the Reetz alkylation of silyl enol ethers with -butyl chloride for which titanium tetrachloride is known to be useful [52]. B, was the Diels-Alder reaction between furan and acetylenedicarboxylic ester for which aluminium trichloride is a good catalyst [53]. C, was a Friedel-Crafts acylation for which aluminium trichloride is the preferred catalyst [54]. The reactions are summarized in Scheme 6. 

The highly regio- and diastereoselective addition of an alkyl and an arylthio group to an olefinic double bond ( carbosulfenylation ) is achieved with arenesulfenyl chlorides and alkyl-chloro-titanium(IV) species (Reetz reagent, from R2Zn/TiCU 5 1 M. T. Reetz, 1987, 1989), Use of the more bulky 2,4,6-triisopropylbenzenesulfenyl chloride improves the yield of the highly versatile alkyl aryl sulfide products. 

Lewis-acid-induced alkylation reactions, employing SN1 electrophiles, has been advanced and reviewed by Reetz (26) and Fleming (27) and their collaborators. 

As an extension of these studies on the use of sulfoximines in asymmetric reductions, BlNOL-derived phosphino sulfoximines of the 105 type were tested in both rhodium-catalyzed hydrogenations (yielding optically active diesters 104 or amino acid derivatives Scheme 2.1.1.35) and palladium-catalyzed allylic alkylations (not shown) in collaboration with Reetz and Gais [81, 82]. Here, enantioselectivities of up to >99 and 66% ee, respectively, were achieved. 

For a recent review on Lewis acid induced a-alkylation of carbonyl compounds, see Reetz, M. T. Angew. Chem. Int. Ed. Engl. 21, 96 (1982). See also Colvin, E. in Silicon in Organic Synthesis , p. 221, London, Butterworths 1981... 

In the alkylation of a-chiral aldehydes with no ability to chelate with organometal-lic compounds such as Grignard reagents, erythro alcohols are usually obtained preferentially according to the Cram s rule [127], and high Cram selectivity can be achieved with alkyltitanium reagents developed by Reetz [128]. In contrast, application of amphiphilic alkylation to a-chiral aldehydes enables one to achieve the hitherto difficult anti-Cram selectivity, affording threo alcohols selectively as shown in Sch. 91 [125]. 

A new method for the size- and morphology-selective preparation of metal colloids using tetraalkylammonium carboxylates of the type NR4 R C02 (R = octyl, R = alkyl, aryl, H) both as the reducing agent and as the stabilizer [Eq. (4)] was reported by Reetz and Maase [42]. 

Studies pertaining to diastereoselectivity in Lewis acid catalyzed alkylations of enol derivatives have been limited. Reetz has reported that r-butylation of l-trimethylsiloxy-4-f-butylcyclohex-l-ene gave an 8S 1S mixture of cis- and frafu-2,4-di-f-butylcyclohexanone, which could result from kinetic equatorial and axial alkylation, respectively. However, equilibration of the products, which would favor formation of the former isomer, was not ruled out. Titanium tetrachloride promoted phenylthiomethylation of the more-substituted TMS enol ether of 1-decalone gave a 4 1 mixture of cis- and rranj-fused 1-deca-lones. In this case, where equilibration of the product could not occur, the diastereoselectivity was similar to that of methylation of the corresponding lithium enolate (49). ... 

The position of alkylation of homoannular silyl dienol ethers is apparently dramatically influenced by the nature of the alkylating agent and catalyst. Reetz and cowoikers reported that 1-trimethylsiloxy-... 

There is no doubt that aldehydes are more reactive than ketones toward nucleophiles. However, both carbonyl substrates are functionalized by activated nucleophiles e.g. RLi or RMgX (X=halogen), with poor chemoselectivity. For example, benzaldehyde is not a dominant species to be alkylated in the coexistence of acetophenone. Reetz and co-workers addressed these difficulties by systematic studies on ligand effects in carbonyl addition reactions of RMgL (L=relatively bulky ligand) [31]. Upon reacting a 1 1 mixture of PhCHO and PhCOMe with 1 equiv of RMgL in a competition experiment, the aldehyde reacted essentially exclusively to form adduct 2-H (Table 2-2, entries 2-A). 

Reetz, M. T., and R. Ostarek, Polymerization of Acrylic Acid Esters Initiated by Tetrabutylammonium Alkyl and Aryl Thiolates, ... 

Reetz has shown that hydride acceptors (e.g. triphenylmethyl tetrafluoroborate) may effect elimination of /8-hydrogen atoms from organolithium and magnesium compounds, to generate olefins under mild conditions.Yields increase from primary through to tertiary metallated compounds. Furthermore, addition of alkyl-lithium reagents to activated olefins (e.g. 1,1-diphenylethylene) followed by hydride abstraction gives the 2-alkyl-l,l-diphenylalkenes. ... 

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