In Grignard reactions

In Grignard reactions, Mg(0) metal reacts with organic halides of. sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand. Pd(0) complexes react more easily with halides of carbons. In other words, alkenyl and aryl halides undergo facile oxidative additions to Pd(0) to form complexes 1 which have a Pd—C tr-bond as an initial step. Then mainly two transformations of these intermediate complexes are possible insertion and transmetallation. Unsaturated compounds such as alkenes. conjugated dienes, alkynes, and CO insert into the Pd—C bond. The final step of the reactions is reductive elimination or elimination of /J-hydro-gen. At the same time, the Pd(0) catalytic species is regenerated to start a new catalytic cycle. The transmetallation takes place with organometallic compounds of Li, Mg, Zn, B, Al, Sn, Si, Hg, etc., and the reaction terminates by reductive elimination. 

A wide variety oi reaetion temperatures and times have been employed in carrying out these reactions in an extreme case tem-teratures of up to ca. 350° were employed. Under these conditions it is quite possible that the actual products isolated were formed as the result of seeondary reactions occurring after the primary products had been formed. Standard procedures for the working up of reaction mixtures obtained in Grignard reactions arc usually followed. 

In Grignard reactions involving GeCl4, complications usually arise because of the possible generation of intermediates like XR2GeMgX. Such intermediates can explain the formation of cyclotetragermanes20. 

Organogallium compounds, 12 361 Organogermanium compounds, 12 554 Organogold compounds, 12 707-708 Organohalogen compounds (AOX), 26 398 Organohalogens, in Grignard reactions, 12 824... 

Physical organic experiments have shown that simple organolithinm reagents exist as aggregates in solution and react with aromatic aldehydes and ketones as a monomer. In most cases, the reactions are initiated by ET, as in Grignard reactions, althongh... 

SCHEME 16. The observed stereochemistry of the reported reactions by the use of (a) chiral ketones and (b) Grignard reagents in Grignard reactions. Asymmetric carbon atoms are denoted by i or 5... 

Perhaps mote frequently used In Grignard reactions than any other representative of its class of substances has been the parent compound... 

The lesser known four-membered cyclic ether, oxacyclobutane (oxe-tane), (CH2)30, also is cleaved readily, but less so than oxacyclopropane. Oxacyclopentane (oxolane, tetrahydrofuran) is a relatively unreactive water-miscible compound with desirable properties as an organic solvent. It often is used in place of diethyl ether in Grignard reactions and reductions with lithium aluminum hydride. 

M. F. Kharesch and O. Reinmuth, in Grignard Reactions of Nonmetallic Substances , Prentice-Hall, New York, 1954. 

For the general experimental method and precautions necessary in Grignard reactions, see Preparation 19. 

The pale yellow colour cannot be removed by redistillation or recrystallisation the coloured product probably contains some amino compound rendering it unsuitable for conversion into a Grignard reagent. A pure white product may be obtained by the following procedure. Dissolve 50 g of the coloured compound in 200 ml of hexane and pass the solution through a column of activated alumina (80-200 mesh dimensions about 9 cm x 3 cm) wash the column with 750 ml of hexane. Remove the hexane by distillation 49 g of pure 2-bromonaphthalene, m.p. 58 °C, remains. This is sufficiently pure for use in Grignard reactions. 

The first system to be studied involved the addition of methyltitanium tri-isopropoxide 6 (one part) to a 1 1 mixture of hexanal 74 and 2-ethylbutanal 75 21). The product ratio 76 77 turned out to 92 8 (95 % conversion), showing that reactions of organotitanium reagents are very sensitive to the steric environment around the reaction center. It is interesting to note that in Grignard reactions a reversed mode of addition is required, i.e., the aldehyde is added to the very basic organometallic reagent, otherwise rapid aldolization sets in. For competition experiments this is unsuitable 21). 

In all of these reactions, a nucleophile adds to a positively polarized carbonyl carbon to form a tetrahedral intermediate. There are three possible fates for the tetrahedral intermediate (1) The intermediate can be protonated, as occurs in Grignard reactions, reductions, and cyanohydrin formation. (2) The intermediate can lose water (or OH), as happens in imine and enamine formation. (3) The intermediate can lose a leaving group, as occurs in most reactions of carboxylic acid derivatives. 

It is worth mentioning that the synthesis of allenes from propargyl halides in Grignard reactions is favored by transition metal catalysis more than by the participation of allenic carbene intermediates in as much as the level of metal impurities in magnesium turnings is not reduced to a minimum, or metal salts such as ferric chloride and other metal chelates such as nickel acetoacetonate are added to the reaction mixture. ... 

For a review on the effect of transition metal catalysis in Grignard reactions see E. Erdik. Tetrahedron, 40, 641 (1984). 

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