Addition of Organometallic Nucleophiles

Even a 1 -alkyne is acidic enough to react with a Grignard reagent. This reaction is the most common method of preparing Grignard reagents derived from these alkynes  

The reaction of Grignard reagents and organolithium compounds with aldehydes and ketones is perhaps the most useful method for the preparation of alcohols. The reaction is conducted under basic conditions and proceeds according to the following general mechanism  

Because these organometallic reagents are powerful nucleophiles, the reaction is irreversible. After the addition is complete, acid is added in the workup step to pro- 

The reaction of an organometallic reagent with formaldehyde produces a primary alcohol  

Reactions with other aldehydes produce secondary alcohols. Although the presence of most other functional groups (OH, NH, carbonyl groups, and so on) must be avoided because they react with Grignard or organolithium reagents, ether and alkene groups can be present  

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In a search for open-chain 1,3-stereo-control, addition of organometallic nucleophiles [MeLi, MeMgBr, Me3ZnLi, Me2CuCNLi2, (PhMe2Si)2CuLi, etc.] to a series of (5-... 

The Michael addition of organometallic nucleophiles to enones in the presence of copper(I) salts produces enolates which on treatment with phenylselenenyl bromide give a-seleno ketones. For example, the reaction of the zirconium enolate of 15 with a mixture of phenylselenenyl bromide and diphenyl diselenide affords a mixture of diastereomeric (2R)- and (2V)-phenylse-leno)cyclopentanones 16 in 50% and 31 % isolated yield, respectively12. The analogous reaction with phenylselenenyl chloride gives only the tram-isomer in 27% yield formation of the cw-product is not observed12. 

In summary, sulfonamides are most commonly prepared by the reaction of amines with sulfonyl halides. Aryl sulfonyl chlorides may be accessed from C-H bonds by chlorosulfonylation, from C-S bonds by oxidation, from C-N bonds by diazotization, or from C-X bonds by metalation. Approaches to all l sulfonamides are more limited as they are typically prepared by either oxidative chlorination of thiols or addition of organometallic nucleophiles to sulfur electrophiles. Traditional sulfonamide preparation has frequently necessitated harsh reagents and conditions, but the development of Pd-catalysed approaches and discovery of new sulfur dioxide sources allow for operationally simple sulfonamide synthesis under mild conditions. Future directions in sulfonamide synthesis will likely involve the direct C-H installation of sulfonamides without the use of hazardous reagents. 

The addition of carbon nucleophile, including organometallic compounds, enolates, or enols, and ylides to carbonyl gro is an important method of formation of carbon-carbon bonds. Such reactions are- ctremely important in synthesis and will be discussed extensively in Part B. Here, we will examine some of the fundamental mechanistic aspects of addition of carbon nucleophiles to carbonyl groups. 

A different approach to chiral oc-hydroxy acids 4 is the nucleophilic addition of organometallic reagents to chiral oc-oxo 4,5-dihydrooxazoles 2, which can be synthesized by oxidation of the corresponding 2-alkyl-4,5-dihydrooxazoles l17,19. 

As with oxathianes 3 (R1 = CH, R2 = H), which bear a close structural resemblance to 17, the addition of organometallic reagents is highly diastereoselective with a predominant chelation-controlled attack of the nucleophile from the Rc-sidc35 -40. In the case of vinylmagnesium bromide a considerable enhancement of the diastereo selectivity could be attained by adding... 

Addition of C-nucleophiles to nitrile oxides is of special interest. There are examples of reactions with both carbanions and neutral carbon nucleophiles. To the former group belong reactions of nitrile oxides with organometallic... 

Nucleophilic addition of organometalic reagents occurs when the nitrone form is in equilibrium with the hydroxylamine form, for instance, in the case of N -benzyl-/V-glycosyl hydroxylamines (Scheme 2.130) (213). 

Addition of organometalic compounds to nitrones is known as an efficient method of enantioselective synthesis of primary amines that can be easily obtained by the reduction of hydroxylamines which are the products of nucleophilic addition. 

Increasing interest is expressed in diastereoselective addition of organometallic reagents to the ON bond of chiral imines or their derivatives, as well as chiral catalyst-facilitated enantioselective addition of nucleophiles to pro-chiral imines.98 The imines frequently selected for investigation include N-masked imines such as oxime ethers, sulfenimines, and /V-trimcthylsilylimines (150-153). A variety of chiral modifiers, including chiral boron compounds, chiral diols, chiral hydroxy acids, A-sull onyl amino acids, and /V-sulfonyl amido alcohols 141-149, have been evaluated for their efficiency in enantioselective allylboration reactions.680... 

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