Magnesium compounds Wittig reaction

Our first example is 2-hydroxy-2-methyl-3-octanone. 3-Octanone can be purchased, but it would be difficult to differentiate the two activated methylene groups in alkylation and oxidation reactions. Usual syntheses of acyloins are based upon addition of terminal alkynes to ketones (disconnection 1 see p. 52). For syntheses of unsymmetrical 1,2-difunctional compounds it is often advisable to look also for reactive starting materials, which do already contain the right substitution pattern. In the present case it turns out that 3-hydroxy-3-methyl-2-butanone is an inexpensive commercial product. This molecule dictates disconnection 3. Another practical synthesis starts with acetone cyanohydrin and penty(magnesium bromide (disconnection 2). Many 1,2-difunctional compounds are accessible via oxidation of C—C multiple bonds. In this case the target molecule may be obtained by simple permanganate oxidation of 2-methyl-2-octene, which may be synthesized by Wittig reaction (disconnection 1). 

The reactivity of organometals increases in the order Li < Na < K alkali metal organometals are more efficient than magnesium and aluminium compounds and the reaction of aryllithium organometals with ketones is more rapid than that of alkyllithium compounds [202], Wittig and Bub [204, 205] postulated the formation of transition complexes with simultaneous nucleophilic attack on the carbonyl and electrophilic attack on the oxygen by the metal. 

Alkyl halides, as well as sulfonates, besides being useful for the preparation of derivatives as shown above, are widely utilized for the preparation of phosphorus derivatives such as R-PPhi Hal , precursors for the generation of Wittig reagents. Alkyl halides are also extremely important as intermediates in the preparation of the most valuable derivatives of oxidation level 0, the organometallic compounds. The required reduction step is usually carried out via direct reaction of the alkyl halides with an active metal such as lithium or magnesium. 

Peterson Alkenation. Trimethylsilylmethyllithium (1) provides an alternative to a Wittig approach for the preparation of methylene compounds from carbonyl precursors. In some cases the use of (1) is superior to the Wittig approach. Condensation of (1) with a carbonyl compound results in the formation of a 8-hydroxysilane. Elimination to the alkene can be acconqtlished by use of acidic or basic conditions (eq 1). acetyl chloride or thionyl chloride can also be used to accomplish this elimination. A wide variety of aldehydes and ketones have been used as substrates in this reaction. The use of cerium(III) chloride has been advocated with reagent (1) to favor nucleophilic addition with enolizable carbonyl corrqtounds. The use of the lithium agent (1) gives superior yields compared to the use of trimethylsilylmethyl-magnesium chloride with cerium, ... 

Reaction of a metallated carbon nucleophile R —M with an organohalogen compound R-X leads to an ate complex 12 [71, 72], the relevance of which in lithium-halogen exchange reactions was postulated as early as 1958 by Wittig [71]. Experimental evidence for this intermediate was subsequently obtained by Reich [73, 74], and in 1986 Famham reported the first isolation of such an (iodine-based) 10-1-2 [75] ate complex [76]. In 1998, Hoffmann reported a related ate complex as an observable intermediate in an iodine-magnesium exchange reaction [77]. In the further course of the reaction, these intermediates are converted to the end products R -X and R-M [78]. 

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