Acylation of alkanes

The Friedel-Crafts acylation of alkanes requires hydride abstraction, which can be induced by the acylium ion itself, to form the corresponding carbocation. This may undergo carbocationic rearrangements prior to a proton loss to form an alkene, which then reacts with the acylating agent. Similar to the acylation of alkenes, the product is an unsaturated ketone. The reaction is limited to alkanes that are prone to undergo hydride transfer. 

Cyclohexane can be acylated with acetyl chloride and AICI3 to yield l-acetyl-2-methylcyclopentene in 37% yield.127 Alkanes, such as 2-methylbutane, cyclohexane, methylcyclopentane, and methylcyclohexane, are easily acylated with a,p-unsaturated acyl chlorides in the presence of A1C13 and a hydride acceptor to afford mono- or bicyclic products after secondary transformations.128 Isoalkanes (isopentane, 2-methylpentane, 3-methylpentane, 2,3-dimethylbutane) undergo diacylation and eventually form pyrilium salts under Friedel-Crafts acylation conditions with acetyl chloride or acetic anhydride.129 

The formation of l-acetyl-2-methylcyclopentene was also observed when either cyclohexane or cyclopentene was reacted by Vol pin and coworkers with an excess of the aprotic organic superacid MeCOCl—2AlBr3 130131 

However, when a 1 1 molar ratio was applied, the corresponding saturated ketone was obtained, albeit in low yield. Cyclopentane, in turn, gives acetylcyclopentane in 60-80% yields. 

Schellhammer, in Methoden der Organischen Chemie (Houben-Weyl), Vol. 7/2a Ketone, E. Muller, ed., Thieme, Stuttgart, 1973, p. 15-370. 

---

The acylation of alkanes has also been known for a long time, but for synthetic purposes is limited to simple substrates. The initial step is hydride abstraction by an acylium ion, a process well established in the presence of a powerful Lewis acid, most commonly an aluminum halide, or strong protic acid. The carbocation so formed can then undergo elimination, possibly after hydride or alkyl migration, to give an alkene which is then acylated. In the presence of excess alkane, saturated ketones are formed by a further intermolecular hydride transfer, whereas with an excess of acyl halide, the product is the (conjugated) unsaturated ketone. -" The synthetic potential is obviously likely to be limited to simple substrates. 

Apart from Bronsted acid activation, the acetyl cation (and other acyl ions) can also be activated by Lewis acids. Although the 1 1 CH3COX-AIX3 Friedel-Crafts complex is inactive for the isomerization of alkanes, a system with two (or more) equivalents of AIX3 was fonnd by Volpin to be extremely reactive, also bringing abont other electrophilic reactions. 

In 1978, Schwartz and Gell found that CO would induce reductive elimination of alkane in various zirconocene alkyl hydride complexes with concurrent formation of Cp2Zr(CO)2 (2) (52,53). It was postulated that CO initially coordinates to the 6-e complex 23 forming the coordina-tively saturated species 24 which can then reductively eliminate alkane and/or rearrange to a zirconocene acyl hydride intermediate. When R = cyclohexylmethyl, methylcyclohexane reductively eliminated and Cp2Zr(CO)2 was isolated in 25% yield. 

Enol Ethers and Esters 0-15 O-Alkylation of carbonyl compounds with diazo alkanes 0-17 Transetherification 0-20 Reaction between acyl halides and active hydrogen compounds 0-23 Transesterification 0-24 Acylation of vinylic halides 0-94 Alkylation with ortho esters 0-107 O-Acylation of 1,3-dicarbonyl compounds... 

In principle, the acylation of aliphatic compounds is analogous with the Friedel-Crafts acylation of aromatics in the sense that a hydrogen of the reacting alkanes, alkenes, or alkynes is replaced by an acyl group to yield ketones, unsaturated ketones, or conjugated acetylenic ketones, respectively. As discussed subsequently, however, the reactions are more complex. The acylation of aliphatics is an important but less frequently used and studied process.11-13... 

The first step in oxidation of alkanes is usually an 02-requiring hydroxylation (Chapter 18) to a primary alcohol. Further oxidation of the alcohol to an acyl-CoA derivative, presumably via the aldehyde (Eq. 17-2), is a frequently encountered biochemical oxidation sequence. 

The porphyrin-iron(III)-peroxo complex [Fe(TPP)02] (163) was prepared by the reaction of K02 with Fen(TPP) in the presence of a crown ether, and characterized by spectroscopic methods [p(0—O) = 806 cm-1]542. This peroxo complex (163) was found to be inactive toward hydrocarbons. However, addition of excess acetic anhydride to (163) dissolved in a benzene-cyclohexane mixture results in the formation of cyclohexanol and cyclohexanone. This reaction is thought to proceed via acylation of the peroxo group, giving iron percarboxylate (164), which decomposes to an Fev-oxo compound (165) capable of hydroxylating alkanes.543 Such a mechanism has been suggested for the hydroxylation of camphor by Pseudomonas cytochrome P-450.544... 

Akhrem et al.390 have reported a unique method for the acylation of aromatics. When alkanes and cycloalkanes (propane, butane, cyclopentane, cyclohexane) are treated with CBr4-2AlBr3 in the presence of carbon monoxide, the intermediate acyl cations react with aromatic silanes to yield acylated products by desilylative acylation [Eq. (5.151)]. The ipso-substitution of trimethylsilane takes place regioselectively,... 

---