Lithium catalysis aldol reactions

You should look upon silyl enol ethers as rather reactive alkenes that combine with things like protons or bromine (Chapter 21) but do not react with aldehydes and ketones without catalysis they are much less reactive than lithium enolates. As with alkylation (p. 674), a Lewis acid catalyst is needed to get the aldol reaction to work, and a Ti(IV) compound such as TiCl4 is the most popular. 

Reetz reported the catalysis by BINOL-TiCl2 of aldol reactions with aliphatic aldehydes [88]. BINOL-TiCli was prepared by treatment of the lithium salt of BINOL with TiCl4 in ether. After removal of the ether the residue was treated with dry benzene and the solid was separated under nitrogen. Removal of the solvent provided the red-brown complex, which was used as the catalyst for the aldol reaction to give 8 % ee. Later, Mukaiyama reported that use of BINOL-Ti oxide prepared from (i-PrO)2-Ti=0 and BINOL resulted in moderate to high enantioselectivity (Sch. 30) [89]. 

Other fates are possible for the enolate formed in the initial conjugate addition and an obvious possibility is an aldol reaction. With an asymmetric catalyst, the combination of three simple molecules leads to one enantiomer of one diastereoisomer of the tandem Michael-aldol product14 83. The catalyst 84 is based on a BINOL A1 complex (see chapters 25, 26). It can be drawn either as a lithium salt with an aluminium cation or, better, as a lithium aryloxide with a Lewis-acidic aluminium atom. This is better because both basic ArCT and Lewis acidity are necessary for catalysis. 

The aldol reaction in carbonyl compounds has its equivalents in 7i-electron deficient heterocycles. In the carbanion approach, lithiated acetophenone added rapidly and regioselectively to 1-substituted 2-pyrimidinones to form the 3,4-dihydro isomer (279) (Scheme 45) <85ACS(B)195>. The adducts are readily oxidized to their aromatic equivalents (280) by DDQ. With the lithium enolate of mesityl oxide, however, equal amounts of the two dihydro isomers were formed <88JOM(338)34l>. In highly 7i-electron deficient heterocyclic systems, aldol reactions will also take place under the influence of acid catalysis such as in the addition of acetone to the pyrimidinone (281) the product is fully conjugated (282) after DDQ dehydrogenation <79ACS(B)150>. 

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