Organomagnesium reagent

Sulfur is more effective than oxygen in stabilizing an adjacent carbanion. Thus, using an equimolar mixture of furan and thiophene, the thiophene is selectively meta-lated v /hen using one equivalent of n-BuLi. 

A filled sp orbital is lower in energy than filled sp or sp orbitals since it is closer to the positively charged nucleus. This imparts sufficiently greater acidity to acetylene and 1-alkynes (pA a 24-26) so that bases such as alkyllithiums, lithium dialkylamides, sodium amide in liquid ammonia, and ethylmagnesium bromide may be used to generate the alkynyl anions (see Section 8.2). 

Although alkyl- and aryllithium reagents usually attack the carbonyl group of a, j3-unsaturated carbonyl compounds (1, 2-addition), conjugate addition (1, 4-addition) is observed with very hindered esters where approach to the carbonyl group is impeded, as in 2,6-di-terr-butyl-4-methylphenyl esters (butylated hydroxytoluene, BHT esters) and 2,6-di-tert-butyl-4-methoxyphenyl esters (butylated hydroxyanisole BHA esters).  

The Grignard reaction, reported in 1900 by Victor Grignard (Nobel Prize, 1912), provides the synthetic chemist with one of the most powerful tools for connecting carbon moieties. 

Formation of Carbon-Carbon Bonds via Organometallic Reagents 

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Organomagnesium reagent capable of reacting with active H compounds or in additions to C X... 

Organolithium and organomagnesium reagents are highly reactive toward most carbonyl compounds. With aldehydes and ketones, the tetrahedral adduct is stable, and alcohols are isolated after protonation of the adduct, which is an alkoxide ion. 

The actual mechanism by which a particular reaction proceeds strongly depends on the nature of the organomagnesium reagent. For instance benzophenone reacts with methylmagnesium bromide by a polar mechanism, while the reaction with t-butylmagnesium chloride proceeds for steric reasons by a SET-mechanism. 

The reaction with organolithium or organomagnesium reagents 9 leads to formation of /3-aminoalcohols 10 ... 

As demonstrated, the organozinc reagent provides exclusively the Cram product, while the organomagnesium reagent shows poor diastereofacial selectivity in the addition to 1 and even reverses the selectivity in the addition to 4. 

While the synthesis of fnnctionalised secondary alcohols and amines can be achieved withont catalyst by the addition of organolithium and organomagnesium reagents to C=N and C=0 gronps, these methods lack a significant functional group tolerance. In order to overcome this limitation and access to more functionalised compounds, the catalytic arylation of aldehydes and imines has been extensively studied [2]. 

If bridged intermediates are involved, the larger steric bulk of secondary systems would retard the reaction. Steric restrictions may be further enhanced by the fact that organomagnesium reagents are often present as clusters (see below). 

As with organomagnesium reagents, there is usually loss of stereochemical integrity at the site of reaction during the preparation of alkyllithium compounds.25 Alkenyllithium reagents can usually be prepared with retention of configuration of the double bond.26,27... 

Without a means to easily control the chirality of benzylic stereocenter, Pettus group members decided to focus on the development of procedures for the construction of adducts without chiral centers. These researchers found that organomagnesium reagents can be used to both generate and consume the o-QM from the corresponding... 

There were several problems to address in developing the conversion of the unsaturated acyl imidazolide 18 to these ketones. The acetylacetonate ligand was found to add to 18 leading to more than 2% of a by-product, believed to be 59 (Figure 3.7), which proved difficult to remove. The reaction also consumes far more organomagnesium reagent than should be necessary 5 equiv are required for complete conversion (the theoretical is 2.0). Also, the reaction provided best results when carried out at low temperature (-35 °C). 

The preparation of ketones proceeds conveniently by reaction of imidazolides with organomagnesium reagents, as shown in Table 14-6 for several examples of purely aromatic, aromatic-aliphatic, and purely aliphatic ketones. The yields are very satisfactory even for purely aliphatic ketones, since in this case, too, alcohol formation is completely suppressed.t851,t861... 

Oximes 509 can be converted to their tosylates 510, but use of a large excess of KOH converts them directly into 27/-azirincs 511 (Scheme 82) <2003JOC9105>. The benzotriazolyl moiety in azirines 511 can be substituted by nucleophiles (organomagnesium reagents, potassium phthalimides, and sodium thiophenoxide) to give disubstituted azirines 512. 

JOC8210>. Condensation of succinaldehyde with arylhydrazines and benzotriazole gives 1-aminopyrrolidines 646 that upon treatment with organomagnesium reagents rearrange to 1,4,5,6-tetrahydropyridazines 647 <1998S1627>. 

Addition of an excess of organolithium or organomagnesium reagents to germanium halides results in the deplacement of the halide ions and the formation of tetra-alkyl and -arylgermanium compounds. Representative examples of these reactions are shown in equations 4 and 5, respectively. 

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