Saturated Grignard reagents

Structural rearrangements are not encountered with saturated Grignard reagents, but allylic and homoallylic systems can give products resulting from isomerization. NMR studies indicate that allylmagnesium bromide exists as a CT-bonded structure in which there is rapid equilibration of the two terminal carbons.101 Similarly,... 

The aldehyde 11 and its a -epimer 15, on reaction with saturated Grignard reagents, afforded separable mixtures of diastereoisomers in which the syn adducts prevailed. 

Steric hindrance on the carbonyl derivative. With a saturated Grignard reagent and a conjugated aldehyde, 1,2-addition is exclusive, except if the R of RMgX is a bulky tertiary group [1-4]. 

Only a few studies have been made on this reaction. Saturated Grignard reagents react with a, -ethylenic thioketones [28,29] to lead to a mixture of several products. They principally result from thiophilic 1,2-addition, thiophilic 1,4-addition, and 5-alkylation [28,29]. 

A series of 8-hydroxy saturated fatty acids were synthesized to explore the effect of chain length on activity. The hydroxyl function was maintained on the eight carbon by starting with 1,8-octanediol and the chain length dictated by a reaction with the appropriate carbon number saturated Grignard reagent. The eighteen carbon 8-hydroxy compound demonstrates the most activity in this series (Fig. 5). 

If the hydrogenation reaction is carried out in the presence of magnesium chloride, the product is the saturated Grignard reagent. The active species is HMgCl, which is formed quantitatively [76] (Scheme 14). 

Structural rearrangements are not encountered with saturated Grignard reagents. Allylic and homoallylic systems can give products resulting from isomeriz-... 

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

Compounds which can formally be considered as anhydro bases can sometimes react with nucleophiles. Thus unsaturated azlactones with Grignard reagents give saturated azlactones (Scheme 50) (65AHC(4)75). 

Kharasch has shown that the presence of a small amount of cuprous chloride favored the conjugate addition of Grignard reagents to a, -un-saturated ketones rather than 1,2-addition. 

In some cases Grignard reagents cause reduction of the iminium salt to the corresponding saturated amine (51a). 

The stereochemical course of reduction of imonium salts by Grignard reagents was found to depend on the structure of the reagent 714). Hydro-boration of enamines and oxidation with hydrogen peroxide led to amino-alcohols (7/5). While aluminum hydrogen dichloride reacted with enamines to yield mostly saturated amines and some olefins on hydrolysis, aluminum hydride gave predominantly the unsaturated products 716). 

In contrast to these ring-opening reactions, it was observed by Horner and Schwahn that 4-arylidene-(isopropylidene and cyclo-hexylidene)-oxazolones react with alkyl Grignard reagents by conjugate addition to give saturated azlactones 29a as the only products [Eq. (18)]. 

An interesting example of the organomagnesium synthesis is to be found in the use of 1,4-addition of the Grignard reagent to 4-alkyl-ideneisoxazol-5-ones (91) to prepare saturated isoxazol-5-ones (92). 

The reaction mixture is diluted with dry tetrahydrofuran (25 ml) and allowed to stand at room temperature for 20 hours. Excess Grignard reagent is quenched by adding a saturated solution of ammonium chloride. The organic layer is separated and the aqueous layer is extracted with ethyl acetate. 

Grignard reagents carry out nucleophilic attack at a saturated carbon when they react with oxiranes => a convenient way to synthesize 1° alcohols. 

Electrolysis of Grignard reagents in ether produces the saturated and unsaturated hydrocarbons to be expected if the anode oxidizes a real or potential carbanion to the corresponding free radical. 

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