Grignard reagents, bonding

Methods of producing B —C bonds include hydroboration, nucleophilic displacement at a boron atom in BX., (X = halogens or B(0R>3) by e.g. a Grignard reagent, and a psewiio-Friedel-Crafts reaction with an aromatic hydrocarbon, BX3, and AICI3. 

The main use of organocadmium compounds is for the preparation of ketones and keto-esters, and their special merit lies in the fact that they react vigorously with acid chlorides of all types but add sluggishly or not at all to multiple bonds (compare addition of Grignard reagents to carbonyl groups). Some t3rpical syntheses are ... 

The reaction of Grignard reagents with a carbonyl group can be understood as an insertion reaction of an unsaturated C=0 bond of the carbonyl group into... 

Another feature of the Pd—C bonds is the excellent functional group tolerance. They are inert to many functional groups, except alkenes and alkynes and iodides and bromides attached to sp carbons, and not sensitive to H2O, ROH, and even RCO H. In this sense, they are very different from Grignard reagents, which react with carbonyl groups and are easily protonated. 

Conjugate addition of vinyllithium or a vinyl Grignard reagent to enones and subsequent oxidation afford the 1.4-diketone 16[25]. 4-Oxopentanals are synthesized from allylic alcohols by [3,3]sigmatropic rearrangement of their vinyl ethers and subsequent oxidation of the terminal double bond. Dihydrojasmone (18) was synthesized from allyl 2-octenyl ether (17) based on Claisen rearrangement and oxidation[25] (page 26). 

The mam synthetic application of Grignard reagents is their reaction with certain carbonyl containing compounds to produce alcohols Carbon-carbon bond formation is rapid and exothermic when a Grignard reagent reacts with an aldehyde or ketone... 

An ability to form carbon-carbon bonds is fundamental to organic synthesis The addition of Grignard reagents to aldehydes and ketones is one of the most frequently used reactions m synthetic organic chemistry Not only does it permit the extension of carbon chains but because the product is an alcohol a wide variety of subsequent func tional group transformations is possible... 

Two of the groups bonded to the hydroxyl bearing carbon of the alcohol are the same because they are derived from the Grignard reagent For example... 

You have already had considerable experience with carbanionic compounds and their applications in synthetic organic chemistry The first was acetyhde ion m Chapter 9 followed m Chapter 14 by organometallic compounds—Grignard reagents for example—that act as sources of negatively polarized carbon In Chapter 18 you learned that enolate ions—reactive intermediates generated from aldehydes and ketones—are nucleophilic and that this property can be used to advantage as a method for carbon-carbon bond formation... 

Crystal stmctures of Grignard reagents do not necessarily correspond to their stmcture in solution. In general, the crystal stmctures (61—64) indicate the reagents are ligated with THF or diethyl ether and are frequentiy observed to be dimers. The Mg atoms in the dimers do not have a Mg—Mg bond instead the dimers are typically held together by a haUde bridge. 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

RM can be a traditional Grignard reagent or an organolithium, 2inc, aluminum, or mercury compound. The Grignard route is employed commercially for production of tertiary phosphines, even though these reactions are subject to side reactions. Yields are often low, eg, 40—50% for (C4H )2P prepared via a Grignard reaction (18). A phosphoms—carbon bond can form from the metathetical reaction of a phosphoms haUde and a pseudohaUde salt. 

In the reaction of aHyl alcohol and Grignard reagent with [P(CgH )2]2-NiCl2 the catalyst, formation of the carbon—carbon bond proceeds at a high yield (22). 

Organometalhcs. Halosilanes undergo substitution reactions with alkali metal organics, Grignard reagents, and alkylaluininums. These reactions lead to carbon—siUcon bond formation. 

Organoantimony Compounds with Five Sb—C Bonds. A number of pentaalkyl- and pentaalkenylantimony compounds have been prepared from tetraalkyl- or tetraalkenylstibonium hahdes and alkyl or alkenyllithium or Grignard reagents, for example ... 

In some instances a carbon-carbon bond can be formed with C-nucleophiles. For example, 3-carboxamido-6-methylpyridazine is produced from 3-iodo-6-methylpyridazine by treatment with potassium cyanide in aqueous ethanol and l,3-dimethyl-6-oxo-l,6-dihydro-pyridazine-4-carboxylic acid from 4-chloro-l,3-dimethylpyridazin-6-(lH)-one by reaction with a mixture of cuprous chloride and potassium cyanide. Chloro-substituted pyridazines react with Grignard reagents. For example, 3,4,6-trichloropyridazine reacts with f-butyl-magnesium chloride to give 4-t-butyl-3,5,6-trichloro-l,4-dihydropyridazine (120) and 4,5-di-t-butyl-3,6-dichloro-l,4-dihydropyridazine (121) and both are converted into 4-t-butyl-3,6-dichloropyridazine (122 Scheme 38). 

The seeond problem is the relationship between the position of the substituent in the pyrazole nueleus and its mobility. In the 1-phenylpyrazole series in their reaetions with Grignard reagents, the bromine reaetivity deereases in the order 5-Br>4-Br>3-Br (B-76MI40402). When an eleetron-withdrawing group is present at the 4-position, the 5-ehloropyrazole is more reaetive than 3-ehloropyrazole, but this has been attributed to bond fixation (Seetion 4.02.3.9). Thus, this problem needs further elarifieation. 

All that has been said in this section applies with equal force to the use of organo-lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleophilic carbon organolithium reagents are another. Both have substantial carbanionic char acter in their- car bon-metal bonds and undergo the same kind of reaction with aldehydes and ketones. 

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