Alkanes from ketone reduction

The yields of ketones, isolated from the reductive debromination of a-bromo-ketones by dicobalt octacarbonyl under basic phase-transfer conditions are good (Table 11.13), but are improved (>95%) by the use of stoichiometric amounts of the quaternary ammonium catalyst. Somewhat unexpectedly, in the case of the reductive dehalogenation of secondary benzylic halides, the yields of the coupled alkanes are... 

Tosylhydrazones can be silylated with (fert-bufyldimethylsilyl)trifluoromethanesulfonate (Me2teriBuSi03SCF3) on the sulfonamide nitrogen. This is how the starting material for a broadly applicable alkane synthesis is produced ( Figure 1.49). Due to their ability to undergo reductive cyanization (Figure 17.69) mesitylene sulfonyl hydrazones allow for a two-step synthesis of nitriles from ketones. 

Catalytic hydrogenation of carbonyl compounds to alkanes is a difficult proposition under normal conditions, although limited success is attainable with aromatic ketones. However, certain enolates derived from ketones have been shown to undergo catalytic reduction to alkanes quite efficiently. For example, enol triflates of ketones are reduced over platinum oxide catalyst to alkanes (equation 56) . Similarly, enol phosphates, conveniently prepared from ketones, can be quantitatively hydrogenated to alkanes (equation 57) . ... 

A method of almost universal applicability for the deoxygenation of carbonyl compounds is the Wolff-Kishner reduction While the earlier reductions were carried out in two steps on the derived hydrazone or semicarbazone derivatives, the Huang-Minlon modification is a single-pot operation. In this procedure, the carbonyl compound and hydrazine (hydrate or anhydrous) are heated (180-220 °C) in the presence of a base and a proton source. Sodium or potassium hydroxide, potassium-t-butoxide and other alkoxides are the frequently used bases and ethylene glycol or its oligomers are used as the solvent and proton source. Over the years, several modifications of this procedure have been used to cater to the specific needs of a given substrate. The Wolff-Kishner reaction works well with both aldehydes and ketones and remains the most routinely used procedure for the preparation of alkanes from carbonyl compounds (Table 9). This method is equally suitable for the synthesis of polycyclic and hindered alkanes. 

In a much less sophisticated system hydrocarbons are being oxidized by OH radicals at the cathode This occurs by simultaneous reduction of Fe(III) and oxygen at cpe. The OH radicals are generated by a Fenton reaction from Fe(II) and cathodically formed hydrogen peroxide. Linear alkanes from C5 to C o are being oxidized to ketones as the only products. The yields decrease with increasing number of carbon atoms and with the Fe(III) concentration. 

Otiier reductive eliminations that form C-H bonds do occur after initial dissociation of a ligand. For example, the elimination of carborane in Equation 8.14, - the elimination of ketone in Equation 8.15, and the elimination of aldehyde in Equation 8.16 aU occur after dissociation of a phosphine ligand. In contrast, die reductive elimination of alkane from the zirconocene alkyl hydride complex in Equation 8.17 occurs after association of ligand. ... 

Both alkanes and alcohols can be produced by the reduction of aldehydes and ketones. However, reactions that produce alcohols generally do not produce alkanes and vice versa. This means that the alcohols do not lie on the reductive pathway to alkanes. Of course, as noted in Chapter 8, alcohols produced by the reduction of aldehydes or ketones can be subsequently converted to alkanes, but the reductive methods for alkanes from the aldehydes and ketones are different from those for alcohols to alkanes. 

By-Products. Almost all commercial manufacture of pyridine compounds involves the concomitant manufacture of various side products. Liquid- and vapor-phase synthesis of pyridines from ammonia and aldehydes or ketones produces pyridine or an alkylated pyridine as a primary product, as well as isomeric aLkylpyridines and higher substituted aLkylpyridines, along with their isomers. Furthermore, self-condensation of aldehydes and ketones can produce substituted ben2enes. Condensation of ammonia with the aldehydes can produce certain alkyl or unsaturated nitrile side products. Lasdy, self-condensation of the aldehydes and ketones, perhaps with reduction, can lead to alkanes and alkenes. 

This section contains dehydrogenations to form alkenes and unsaturated ketones, esters and amides. It also includes the conversion of aromatic rings to alkenes. Reduction of aryls to dienes is found in Section 377 (Alkene-Alkene). Hydrogenation of aryls to alkanes and dehydrogenations to form aryls are included in Section 74 (Alkyls from Alkenes). 

Typically, solvents are screened to identify one that gives optimal results. Assuming that the substrate and catalyst are soluble, solvent polarities varying from alkanes, aromatics, halogenated, ethers, acetonitrile, esters, alcohols, dipolar aprotic to water have been used. An example of this, using a ketone and the rhodium cp TsDPEN catalyst, is shown in Table 35.3. Further optimization of this reaction improved the enantiomeric excess to 98%. A second example involved the reduction of 4-fluoroacetophenone in this case the enantioselectivity was largely unaffected but the rate of reduction changed markedly with solvent. Development of this process improved the optical purity to 98.5% e.e. 

Starting from isolated hydrazones, reduction to the corresponding hydrocarbons by treatment with base in an aprotic solvent takes place at temperatures significantly below the 200 °C of the Huang-Minlon modification of the Wolff-Kishner reduction. However, hydra-zones cannot be prepared in a one-step reaction between a ketone and hydrazine, since usually azines (R1R2C=N=N=CR1R2) are formed instead. However, semicarbazones are hydrazone derivatives that are easily accessible by the reaction of a ketone with semicarbazide (for the mechanism, see Table 9.2). Semicarbazones can be converted into alkanes with KO/Bu in toluene at temperatures as low as 100 °C. This method provides an alternative to the Wolff-Kishner reduction when much lower than usual reduction temperatures are desirable. 

The wide distribution of PKSs in the microbial world and the extreme chemical diversity of their products do in fact result from a varied use of the well-known catalytic domains described above for the canonical PKS systems. Taking a theoretic view of polyketide diversity, Gonzalez-Lergier et al. (41) have suggested that even if the starter and extender units are fixed, over 100,000 linear heptaketide structures are possible using only the 5 common reductive outcomes at the P-carbon position (ketone, (R- or S-) alcohol, trans-double bond, or alkane). Recently, it has become apparent that even this does not represent the upper limit for polyketide diversification. To create chemical functionalities beyond those mentioned above, nature has recruited some enzymes from sources other than fatty acid synthesis (the mevalonate pathway in primary metabolism is one example) not typically thought of as type I PKS domains. Next, we explore the ways PKS-containing systems have modified these domains for the catalysis of some unique chemistries observed in natural products. 

Ra-NL A mild procedure for deoxygenation of aldehydes or ketones is via desulfurization of their thioacetal derivatives. For example, reduction of thioacetals with Ra-Ni, derived by treatment of an Ni-Al alloy with NaOH, produces the corresponding alkane moieties. The hydrogen atoms in the deoxygenated product come from the hydrogen gas adsorbed on the Ra-Ni surface during its preparation. 

Waxes mainly function as protective coatings, such as those found on leaf cuticles. They are mixtures of many constituents with high melting points, important members being esters of fatty acids with straight-chain saturated alcohols (fatty alcohols). The fatty acids and alcohols in these wax esters have similar chain lengths, mainly in the range C24 to C28. They have predominantly an even number of carbon atoms because the alcohols are biosynthesized from fatty acids by enzymatic reduction (Eqn 2.7). Lesser amounts of ketones, branched alkanes and aldehydes are present. 

The first traceless linker was developed by Kamogawa and coworkers in 1983 [82]. Starting from a polymer-bound sulfonylhydrazine, sulfonylhydrazone resin 88 was formed by reaction with ketones or aldehydes. The cleavage step was conducted either by reduction with sodium borohydride or lithium aluminium hydride to yield alkanes 89 or by treatment with base to give the corresponding alkenes 90 in a Bamford-Stevens reaction (Scheme 16.20). This work was a pioneering approach in the field of traceless tinkers. 

---