Regioselectivity enolate alkylation

Ketones, in which one alkyl group R is sterically demanding, only give the trans-enolate on deprotonation with LDA at — 72°C (W.A. Kleschick, 1977, see p. 60f.). Ketones also enolize regioselectively towards the less substituted carbon, and stereoselectively to the trans-enolate, if the enolates are formed by a bulky base and trapped with dialkyl boron triflates, R2B0S02CF3, at low temperatures (D A. Evans, 1979). Both types of fraiu-enolates can be applied in stereoselective aldol reactions (see p. 60f.). 

Simmons-Smith regioselective cyclopropanation of a-enone alkyl enol ethers also provided 1-alkoxyvinylcyclopropanes in high yields43 . 

The use of oxygen-containing dienophiles in the form of silyl enol ethers, or ketene acetals has attracted considerable attention [66]. However, alkyl enol ethers are the most extensively employed dienophiles. The regioselectivity in the [4 + 2] cycloaddition step can be predicted in a straightforward way by FMO analysis. The larger coefficient in the LUMO of the nitroalkene (at the 3-carbon) will align with the... 

Low molecular mass enol esters (e.g. acetates H.O. House, 1965) or enol ethers (e.g. silyl ethers H.O. House, 1969) of ketones can be synthesized regioselectively and/or separated by distillation. Treatment with lithium alkyls converts them into the corresponding lithi-... 

Other methods for the regioselective SN2-opening of vinyloxiranes include intramolecular enolate addition for formation of cyclohexane systems [135, 136] and Friedel-Crafts alkylations [49, 137, 138]. 

Stable enolates such as diethyl malonate anions react with allyl sulfones (or acetates) in the presence of nickel complexes to give a mixture of the a- and /-product83. The regioselectivity is generally poor in the nickel-catalyzed reaction, but the molybdenum-catalyzed reaction is selective for alkylation at the more substituted allylic site, thereby creating a quaternary carbon center84. 

Ketone imine anions can also be alkylated. The prediction of the regioselectivity of lithioenamine formation is somewhat more complex than for the case of kinetic ketone enolate formation. One of the complicating factors is that there are two imine stereoisomers, each of which can give rise to two regioisomeric imine anions. The isomers in which the nitrogen substituent R is syn to the double bond are the more stable.114... 

The intermediate enolate or enol ether from the initial reduction of an enone may be alkylated in situ (Eq. 281).455 / -Substituted cyclopentenones may be asymmetrically reduced and alkylated459 (see section on asymmetric reductions of enones). Enolates may also be trapped with an aldehyde in a reductive aldol condensation of an enone with an aldehyde,455 permitting a regioselective aldol condensation to be carried out as shown in Eq. 282.455 This class of reductive aldol condensation reactions can also occur in a cyclic manner (Eq. 283).460... 

The intermediate enol silyl ether permits further regioselective substitutions such as bromination followed by dehydrobromination (Eq. 81)49> and alkylation (Eqs. 82 93) and 83 103)). Thus, in addition to activating the rearrangement, the oxygen substituent regioselectivity creates an enol silyl ether, a powerful enolate synthon. 

Two consecutive enolate alkylations were utilized to generate the quaternary carbon atom (Scheme 38). Alcohol 238 was transformed into the protected hydroxy enone 244. Regioselective deprotonation at the a-position of the ketone 244 led to a cross-conjugated enolate that was alkylated with the allylic iodide 245. The vinyl silyl moiety in 245 represents a masked keto group [127]. The choice of the TBS protecting group for the hydroxyl group at of 244 was crucial in order to prevent the deprotonation at the y-posi-... 

Tab. 10.3 The scope of the regioselective rhodium-catalyzed allylic alkylation with copper(l) enolates.

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