And Grignard formation

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). 

In terms of cost, the effectiveness of the catalytic cycle in the ring closure makes this process economical in palladium. The first three steps in the reaction sequence -- ring opening of an epoxide by a Grignard reagent, converison of an alcohol to an amine with inversion, and sulfonamide formation from the amine — are all standard synthetic processes. 

Formation of C—Nu The second mode of nucleophilic addition, which often occurs with amine nucleophiles, involves elimination of oxygen and formation of a C=Nu bond. For example, aldehydes and ketones react with primary amines, RNH2, to form imines, R2C=NR. These reactions proceed through exactly the same kind of tetrahedral intermediate as that formed during hydride reduction and Grignard reaction, but the initially formed alkoxide ion is not isolated. Instead, it is protonated and then loses water to form an imine, as shown in Figure 3. 

The patent describes the formation of complex metal chelates by treatment of the ketoester simultaneously with an alcohol and a metal to effect trans-esterification and chelate formation by distilling out the by-product ethanol [1], This process was being applied to produce the zinc chelate of 2-tris(bromomethyl)ethyl acetoacetate, and when 80% of the ethanol had been distilled out (and the internal temperature had increased considerably), a violent decomposition occurred [2], This presumably involved interaction of a bromine substituent with excess zinc to form a Grignard-type reagent, and subsequent exothermic reaction of this with one or more of the bromo or ester functions present. 

The report by Luche and coworkers that ultrasonic waves from a common ultrasonic laboratory cleaner aid the formation of organolithium and Grignard reagents and also improve the Barbier reaction spurred much of the current interest in the synthetic applications of ultrasound(lO) ... 

Chlorodialkylphosphines are important synthetic intermediates in organophosphorus chemistry. In the chemical literature there is a widespread view that the simple one-step Grignard method is not suitable for the preparation of these compounds because of dominant trisubstitution and the formation of difficultly separable mixtures.12 Although this is true for the w-alkyl compounds, the present preparation demonstrates that in the case of branched primary alkyl compounds and secondary and tertiary alkyl compounds the method can be very convenient and can give pure products. The submitters have prepared 13 chloro-diisobutylphosphine (45-50%), chlorodi-sec-butylphosphine (75-80%), chlorodi-f-butylphosphine (65-70%), and chlorodicyclo-hexylphosphine (60-65%) in analogous manner. 

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