Organolithium compounds, 1,4-addition with ketones

Fig. 10.35. Preparation of a tertiary alcohol by the addition of a Grignard reagent or an organolithium compound to a ketone and subsequent workup of the reaction mixture with no more than a weak acid (not shown) or with a corresponding buffer solution (as given here).

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Since Lewis base additives and basic solvents such as tetrahydrofuran are known to deaggregate polymeric organolithium compounds, (21,23,26) it was postulated that ketone formation would be minimized in the presence of sufficient tetrahydrofuran to effect dissociation of the aggregates. In complete accord with these predictions, it was found that the carbonation of poly(styryl)lithium (eq. 9), poly(isoprenyl)-lithium, and poly(styrene-b-isoprenyl)lithium in a 75/25 mixture (by volume) of benzene and tetrahydrofuran occurs quantitatively to produce the carboxylic acid chain ends (8 ). 

Alkenyl trityl ketones, prepared by reaction of 1 with a ketone followed by dehydration, undergo exclusive conjugate addition on reaction with organolithium compounds. The adducts are cleaved to primary alcohols on reduction with LiB(C2H5)3H. 

A smooth 1,2-addition is almost always observed in the reaction of a,/J-unsaturated ketones with organolithium compounds (Figure 10.31, bottom). Only in extreme cases such... 

Fig. 10.31. Competition of 1,2- and 1,4-addition in the reaction of organolithium compounds and Grignard reagents with ,/J-unsaturated ketones a phenomenological view.

Fig. 10.32. Competition between 1,2- and 1,4-additions in the reaction of organo-lithium compounds with a,/3-unsaturated ketones, depending on the structure of the organolithium compound.

The reaction of the solvent-separated Lewis-acidic ion pair C with cyclohexenone is the only multiple-step addition in Figure 10.32. It does not involve the cyclohexenone itself, but its (solv)3Li complex E, which, of course, is the better electrophile. The carbanion R R2R3C may now choose between both the 1,2- and the 1,4-addition. The former proceeds via transition state F, the latter via transition state G. These transition states are about equal in energy, since there is a close (solv), I Tl /(/ contact in both cases. This is why the reaction of organolithium compounds of type C and tt,/i-unsaturated ketones typically leads to a mixture of 1,2- and 1,4-addition products. 

Finally, the addition of Grignard reagents or organolithium compounds to ketones gives tertiary alcohols when one works up with a weak acid (example Figure 10.35). 

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