Carbenes from acyl chlorides

Interactive mechanism for carbene formation from acyl chlorides with diazomethane... 

The main synthetic application of the Wolff rearrangement is for the one-carbon homologation of carboxylic acids.242 In this procedure, a diazomethyl ketone is synthesized from an acyl chloride. The rearrangement is then carried out in a nucleophilic solvent that traps the ketene to form a carboxylic acid (in water) or an ester (in alcohols). Silver oxide is often used as a catalyst, since it seems to promote the rearrangement over carbene formation.243... 

A free carboxylic acid group also enhances the antibacterial spectmm in the penicillin series. Acylation of 6-APA (2-4) with the half-acid chloride (6-1) from benzyl phenylmalonate leads to the amide (6-2). Removal of the benzyl protecting group by catalytic hydrogenation [8] or by enzymatic hydrolysis [9] affords carben-cillin (6-3). A similar sequence starting with 3-thiophenylmalonic acid leads to the considerably more potent analogue ticarcillin (6-4) [10]. 

Carbenes have divalent carbon with a lone pair and hence only six electrons in the outer shell of the carbon atom. They are normally electrophilic and can form two bonds at once with a re-system.7 One way to make carbenes is by loss of nitrogen from diazocompounds such as diazoketones 33. The formation of very stable nitrogen is initiated by heat or light and compensates for the formation of the unstable carbene 30. Diazoketones are easily made by acylation of diazomethane with an acid chloride 31. Loss of a very acidic proton from the diazonium salt 32 gives 33. Normally the diazoketone and the alkene are combined and treated with heat or light.8... 

A complementary access to alkoxy- and aminocarbene complexes ( Semmelhack-Hegedus route ) involves the addition of the pentacarbonylchromate dianion 18 (obtained from the reduction of hexacarbonylchromium with C8K) to carboxylic acid chlorides and amides [27] (Scheme 10). While alkylation of acyl chromate 19 leads to alkoxycarbene complexes 12, addition of chromate dianion 18 to carboxylic amides generates the tetrahedral intermediates 20, which are deoxygenated by trimethylsilyl chloride to give amino carbene complexes 14. 

Cyclopropanation reactions of nonheteroatom-stabilized carbenes have also been developed. The most versatile are the cationic iron carbenes that cyclopropanate alkenes with high stereospecificity under very mild reaction conditions. The cyclopropanation reagents are available from a number of iron complexes, for example, (9-alkylation of cyclopentadienyl dicarbonyliron alkyl or acyl complexes using Meerwein salts affords cationic Fischer carbenes. Cationic iron carbene intermediates can also be prepared by reaction of CpFe(CO)2 with aldehydes followed by treatment with TMS-chloride. Chiral intermolecular cyclopropanation using a chiral iron carbene having a complexed chromium tricarbonyl unit is observed (Scheme 61). 

The acyl cation 2a or acylium ion 2b is a familiar intermediate in the Friedel-Crafts reaction. It is easy to make (acid chloride + Lewis acid 1) and it can be observed by NMR as it expresses the natural reactivity pattern of the acyl group. The acyl anion by contrast has umpolung or reverse polarity.1 One might imagine making it from an aldehyde by deprotonation 3 and that it would be trigonal 4a or possibly an oxy-carbene 4b. Such species are (probably) unknown and their rarity as well as their potential in synthesis has led to many synthetic equivalents for this elusive synthon. The acyl anion, the d1 synthon, is the parent of all synthons with umpolung2 and should perhaps have been treated before the homoenolates dealt with in the previous chapter. 

Related acetoxy-substituted carbene complexes have been prepared by acylation of anionic metal acyl complexes with acetyl chloride (Connor and Jones, 1971a). The silylation of anionic acyl complexes was used to prepare (CO)5CrC[OSi(CH3)3]CH3 (Fischer and Moser, 1968a). Phenoxy-substituted carbene complexes have been obtained from the reaction of anionic acyl com-... 

Hydroxy carbene complexes 161 and 162, formed in the same reaction mixture by the abstraction of chloride from an acyl complex, are reported (Scheme 39). X-ray structures of both complexes show crystallographically imposed symmetry, and hence bond lengths that are intermediate between the extremes of Pt-C and Pt=C (and G-O and C=0). 

Scheme 21). It involves the initial formation of anionic acyl complexes by addition of Li[GH2R] reagents to the carbonyl ligand, which, by reaction with acetyl chloride, generate the vinylidenes via spontaneous loss of MeC02H from intermediate acyl(oxy) carbenes. " ... 

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