Reaction of Organometallic Reagents with Aldehydes and Ketones

10 Reaction of Organometallic Reagents with Aldehydes and Ketones 

Treatment of an aldehyde or ketone with either an organolithium or Grignard reagent followed by water forms an alcohol with a new carbon-carbon bond. This reaction is an addition reaction because the elements of R and H are added across the n bond. 

This reaction follows the general mechanism for nucleophilic addition (Section 20.2A)—that is, nucleophilic attack by a carbanion followed by protonation. Mechanism 20.6 is shown using R MgX, but the same steps occur with organolithium reagents and acetylide anions. 

In Step [1], the nucleophile (R ) attacks the carbonyl carbon and the % bond cleaves, forming an alkoxide. This step forms a new carbon-carbon bond. 

The overall result is addition of (R ) (from R MgX) and (from H2O) to the carbonyl group. 

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Reaction of organometallic reagents with aldehydes and ketones... 

The carbonyl group of acid derivatives reacts with the nucleophilic carbanion available from organo-metallic reagents. However, the reactions of the individual classes of compounds are not as straightforward as the addition reactions of organometallic compounds with aldehydes and ketones. Addition of a carbanion to the acyl carbon atom generates a tetrahedral intermediate that can decompose to give a ketone that will react further with another equivalent of the carbanion. 

To be accurate, the definition should be restricted to asymmetric reactions catalyzed by a combination of l,r-binaphthalene-2,2 -diol (BINOL, 4) and Ti(0 -Pr)4. Nonetheless, this chapter will give some background on non-chiral Lewis acid promoters, and include other asymmetric catalytic systems. We will not discuss the allylations that are promoted by Lewis bases, which are reviewed elsewhere, nor cover the reactions with other electrophiles. Excellent reviews already exist on "Selective Reactions Using Allylic MetaM and Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , as well as in the comprehensive monograph "Modern Carbonyl Chemistry. The use of BINOL-based catalysts in other fields of organic synthesis has also been reviewed. ... 

This book chapter is limited to Lewis acid-mediated reactions, and does not discuss the important field of Lewis base-mediated allylations, nor does it describe the reactions of allylsilanes with other electrophiles such as epoxides, imines, and allyl-X (X = -Cl, -OR, -OAc). The SaJcurai reaction has been covered under different forms in reviews focusing on The Stereochemistry of the Sakurai reaction , Intramolecular Addition Reactions of Allylic and Propargylic Silanes ," Selective Reactions Using Allylic Metals , Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , and Modem Carbonyl Chemistry . ... 

Reactions of organometallic derivatives with ketones, which are less electrophilic than aldehydes, usually require an equimolar amount of a chiral ligand. The first catalytic enantioselective addition of an organometallic reagent, namely ZnPh2, to dialkyl and aryl alkyl ketones was reported in 1998 by Dosa and Fu (Scheme 110).288 The procedure... 

The purpose of this review is to provide a summary (through to the end of 1988) of the uncatalyzed reactions of type I and type III allyl organometallics with C X electrophiles. Most of the examples involve aldehydes and ketones, but the reactions of allyl organometallics with imines are also covered. Because the focus of this review is on selectivity and synthetic efficiency, this review is not intended to be as comprehensive as an Organic Reactions chapter or a Chemical Reviews article. Rather, we have attempted to define and illustrate the factors that influence stereoselectivity, to provide access to the most pertinent literature, and, most importantly, to provide a basis for selection of an allyl organometallic reagent for application in specific synthetic problems. 

Thioketene Acetals. Anion (1) reacts with aldehydes and ketones to provide the corresponding thioketene acetals aryl and unsaturated aldehydes and ketones are good substrates for this reaction (eqs 3 and 4). Enolizable alkyl ketones also react to provide thioketene acetals (eq 5). Alternative methods for the preparation of these cyclic thioketene acetals involve the use of phospho-nate derivatives, mixed zinc-titanium organometallic reagents, and iV,iV-dimethyl thioamides. The phosphonate reagents are more nucleophilic than (1) and are superior when competitive deprotonation is a problem. 

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