Organometallic addition to ketones

I. ORGANOMETALLIC ADDITIONS TO KETONES, CONJUGATED KETONES AND EPOXIDES... 

Organometallic compounds or carbanions undergo a number of reactions in which the carbanion or carbanion-like moiety of the organometallic compound acts as a nucleophilic displacing agent. Examples are the formation of hydrocarbons from alkyl halides, alkyl halides from halogens, and ketones from acid chlorides or esters. The latter two reactions are closely related to the base-catalyzed condensations and are perhaps additions as well as displacement reactions. Related addition reactions are the carbonation of organometallic compounds and the addition to ketones or aldehydes. 

Addition of organometallic reagent to ketone preparation of tertiary alcohols... 

Readily available THF solutions of LnCl3,2LiCl (Ln = La, Ce, Nd) have been found to be superior promoters for the addition of various organometallic reagents to ketones.85 They also catalyse efficiently the addition of organomagnesium compounds to imines. 

Oxidative rearrangement of cyclopropylearbinoh to, y-enoues Tertiary cyclopropylcarbinols (1), which can be prepared by addition of cyclopropyl organometallic reagents to ketones, are oxidized by PCC (5 equiv.) mainly to /3,y-enones (2). The related reagent C5H5NHCr03BF4 is equally effective. Traces... 

The construction of -silyl divinyl ketones in many different structural settings has been weU developed. The four principal connections outlined in Scheme 16 are as follows path a, vinyl organome-tallic addition to 3-trimeAylsilyl-2-propenal path b, 3-trialkylsilylvinyl organometallic" addition to enals path c, palladium-catalyzed carbonylation/coupling of 2-trimethylsilylvinyltrimethylstan-nane and path d, acylation of a B-silyl copper reagent. 

Reaction of 1-lithiocyclopropyl phenyl sulphide (123) with 4-t-butylcyclohexanone produces an adduct as a 99 1 mixture of two isomers. By analogy to organometallic addition to this ketone, the stereochemistry is assumed to result from equatorial attack. Treatment of the adduct with one equivalent of anhydrous stannic chloride followed by hydrolysis produces primarily cyclobutanones (equation 94) ... 

Patterson has prepared ethyl ketone (20) without racemization and in good overall yield by the sequence shown in Scheme 7. The preparation of (20) by standard organometallic addition to the corresponding aldehyde followed by Swem oxidation resulted in substantial racemization. ... 

Many other types of organometallics which are not acylated directly acid chlorides and which do not undergo addition to ketones may still transmetallate into the acylpalladiumfll) complex. Simple alkyl organomercurials have been acylated in this fashion to give moderate to good yields of ketones. " Larock has studied the palladium-catalyzed acylation of vinylmercury(II) compounds with acyl halides (equation 104). The reaction was only modestly productive and could not compare to the yield provided by aluminum chloride catalysis. 

The diastereoselectivities of addition of organometallic compounds to ketones and aldehydes are often quite poor (2 1), and there are numerous cases in which anti-Felkin-Anh selectivity is observed, but the rule is widely invoked anyway. 

The YbCOTflj-catalyzed organometallic addition to a-alkoxy ketones favors a nonchelation transition state. ... 

As with aldehydes, catalytic additions to ketones are more promising with less polar organometallics and some enantioselective catalytic organozinc additions to ketones have been developed [96,97]. For the synthesis of efavirenz (23), stoichiometric amounts of chiral zinc alkoxide additives proved to be highly useful. 

Review Stereochemistry of organometallic compound addition to ketones. 

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