Ketones, diazo alkylation

Reaction of halo ketones or diazo ketones with boranes 10-112 Carbonylation of alkyl halides... 

A number of these alkylation reactions are illustrated in Scheme 9.2. Entries 1 and 2 are typical examples of a-halo ester reactions. Entry 3 is a modification in which the highly hindered base potassium 2,6-di-f-butylphenoxide is used. Similar reaction conditions can be used with a-halo ketones (Entries 4 and 5) and nitriles (Entry 6). Entries 7 to 9 illustrate the use of diazo esters and diazo ketones. Entry 10 shows an application of the reaction to the synthesis of an amide. 

Acceptor-monosubstituted diazomethanes can be further converted into other types of diazo compound. C-Acylation of diazoacetic esters generally requires very reactive acylating agents, such as acid chlorides [969,970] or bromides [971]. C-Alkylations of acyldiazomethanes are best accomplished by metallation followed by treatment with a carbon electrophile [972-977], C-alkylation can also occur without any base if sufficiently electrophilic aldehydes or ketones are used [973,978 -982] or if the alkylation proceeds intramolecularly [983]. 

This general procedure is effective for the preparation of many types of phenylhydrazones. For example, a substituted diazo compound can be employed.2 Alkylated acetoacetic esters 8 and ethyl benzoylacetate 4 may be used. For the higher homologs, the a-formyl derivatives of ketones may be used in place of ethyl acetoacetate.6 6 Ethyl pyridylacetates may also be substituted for ethyl acetoacetate.7 The products in these cases are the phenylhydrazones of 2-acylpyridines. 

Reaction of halo ketones or diazo ketones with boranes 0-102 Carbonylation of alkyl halides 0-104 Reaction between acyl halides and organometallic compounds 0-105 Reaction between other acid derivatives and organometallic compounds... 

Benzyl ketones. Benzyl ketones can be prepared by alkylation of benzene with an a-diazo ketone catalyzed by Rh(02CCF3)2 at 25° followed by workup with TFA.1... 

With 0,-y-unsaturated a -diazo ketones, the resulting [2.1.0]-bicyclic systems (40) were quite unstable and underwent a [2 + 2] cycloreversion to generate ketenes (41), which were then trapped by nucleophiles (Scheme 7). The overall scheme has been named a vinylogous Wolff rearrangement and offers a novel entry to products usually derived from a Claisen rearrangement.102 A recent report describes its application for functionalized angular alkylation in fused ring systems.103 In contrast, the intramolecular re-... 

Thus, the reaction of both aryl (Table 9, entries 1-3) and alkyl diazo ketones (entries 5 7,... 

The construction of the tetracyclic diterpenoids has continued to attract attention. The intramolecular alkylation of an olefin by the acid-catalysed reaction of y5-unsaturated diazo-ketones has been used ° to generate ring D in the step (194)->(195) -i- (196). A benzocyclobutane route based on the thermal cyclization of (197) to (198) has been developed for the synthesis of the beyerane skeleton. A stereoselective synthesis of stachenone, based on a series of... 

Thus, the reaction of both aryl (Table 9, entries 1-3) and alkyl diazo ketones (entries 5-7, 9-11) with (HF) /pyridine and a halide source gives a-fluoro-a-halo ketones. The best yields are generally obtained in the case of the fluoroiodo derivatives (entries 3, 7 and 11). Diazo... 

An extension of this reaction has been the use of other aliphatic diazoalkanes. Benzaldehyde and the appropriate diazo compound give propiophenone, butyrophenone, and valerophenone in almost quantitative yield. Furylaldehyde also reacts to form furyl alkyl ketones ... 

The action of hydrogen bromide or hydrogen chloride on diazo ketones represents a general preparative method (50-90%) for pure halomethyl alkyl, halomethyl aryl, or halomethyl heterocyclic ketones. N ... 

The method has been adapted to the formation of l)fs-diazoacetylalkanes from dibasic acid chlorides. Diazo ketones have been obtained from acyl chlorides containing a /Sj y-double bond, an ester group, and certain heterocyclic and aryl nuclei having alkyl, methoxyl, and nitro substituents. On the other hand, functional groups such as phenolic hydroxyl, arylamino, aldehyde, active methylene, and a,/S-unsaturated linkages may interfere. The method is ideal for application to complex molecules. 

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