Ketones parent hydrides

Among the rare reports of chemical transformation of substituents attached to the ring, the total reduction of an aromatic ketone linked at C-l (lithium aluminium hydride (LAH)), then Et3SiH/trifluoroacetic acid (TFA), overall yield 20%) is of interest <1998H(48)1015>. One example related to Wittig olefination of the 1-formyl derivative of the parent heterocyle was reported to occur in low yield <2001CPB799>. 

The reduction of ketones with silicon hydrides has been occasionally performed by radical chemistry for a synthetic purpose. The radical adduct is stabilized by the a-silyloxyl substituent and for RsSi (R = alkyl and/or phenyl) the hydrogen abstraction from the parent silane is much slower than a primary alkyl radical (cf. Chapter 3). On the other hand, (TMS)3SiH undergoes synthetically useful addition to the carbonyl group and the reactions with dialkyl ketones afford yields > 70% under standard experimental conditions, i.e., AIBN, 80-85 °C [45,51]. Reaction (5.25) shows as an example the reduction of 4-tcrt-butyl-... 

Hydrazones treated with alkalis decompose to nitrogen and hydrocarbons [845, 923] Woljf-Kizhner reduction) (p. 34), and p-toluenesulfonylhydra-zones are reduced to hydrocarbons by lithium aluminum hydride [812], sodium borohydride [785] or sodium cyanoborohydride [813]. Titanium trichloride hy-drogenolyzes the nitrogen-nitrogen bond in phenylhydrazones and forms amines and ketimines which are hydrolyzed to the parent ketones. Thus 2,4-dinitrophenylhydrazone of cycloheptanone afforded cycloheptanone in 90% yield [202]. 

It is important to recognise that it is only through alkoxy/acetoxy interchange around the parent triacetoxyborohydride that a sufficiently reactive hydride donor can be generated that can perform the ketone reduction at an acceptable rate. Ordinarily, Me4NBH(OAc)3 will reduce ketones exceedingly slowly. 

Ketone acetals may be oxidized by hydride transfer, using trityl fluoroborate (see also Part II, Chap. 2, p. 388). ° Ethylene acetals of steroidal ketones afforded the parent ketones in good yield, under non-polar conditions (in CH2CI2 at room temperature). The proposed mechanism (Scheme 3) results in oxidation... 

The phenolic substance previously stated to be formed when codeinone is allowed to stand in hydrochloric acid, to have the composition Cl8Ha04N [3], and to be phenolic has now been identified as 8-hydroxy-dihydrocodeinone [B], which is formed from codeinone by the addition of a molecule of water to the double bond. Reduction of [B] catalytically or with lithium aluminium hydride affords 8-hydroxydihydrocodeine G], which is not oxidized by periodates, thus eliminating formula [D] for the parent ketone. 

Reactions on the three-carbon bridge of oxabicyclo [3.2.1] compounds have been reported but less systematically studied. Because the majority of these compounds are derived from oxyallyl cation cycloadditions, most experiments on the three-carbon bridge involve addition to the bicyclic ketone. The parent oxabicyclo[3.2.1] ketone 90 undergoes reduction with bulky hydride sources such as L-selectride to generate the endo alcohol, Eq. 68 [112]. Presumably, the selectivity is due to equatorial attack of the hydride at the ketone of the pyran-one in a pseudo chair conformation. The exo alcohol is prepared from the endo alcohol by a Mitsunobu inversion-hydrolysis sequence [113]. 

The Stork-Dolfini synthesis of the amino ketone 458 requires some 11 steps clearly, this is an area for improvement. One method used has been that of methyl vinyl ketone annelation (237). This procedure had been used previously in a synthesis of mesembrine (238) involving 2- -rolines. Stevens hoped to extend this technique to endocyclic enamines to give compounds in the octahydroquinolone series. 3-Ethylpiperid-2-one (549) was prepared from the y-lactone 550 according to standard procedures (239). N-Benzylation followed by reduction with diisobutyl-aluminum hydride (DIBAL) gave enamine 473. Addition of the enamine to methyl vinyl ketone (551) gave an almost quantitative yield of a hydroquinoline 552, which could be readily debenzylated to the known amino ketone 458. As with the Stork method of synthesis, this route to the Aspidosperma nucleus is efficient for the parent compounds but appears to lack the potential for diversification required to synthesize the more complex alkaloids such as vindoline (101) or even tabersonine (28). 

Both ligand 171 and its parent, (iS)-P-Phos (Ar = Ph), as their complexes with in 5/tM-generated CuH, have been studied in asymmetric hydrosilylations of halogen-containing aryl ketones. That is, a variety of ketones bearing either chloride or bromide in the a-, 3-, or y-positions undergo 1,2-carbonyl reduction in toluene at -20 C, using phenylsilane as the source of hydride. Enantiomeric excesses t5 ically exceed 90%, as illustrated by the examples below. 

The thioenol ethers are stable towards base and lithium aluminium hydride -but are reconverted to the parent compound on dilute acid hydrolysis. Raney nickel desulphurization can be used to form the diene . Hydrogen peroxide oxidation will convert the acid-labile thioenol ether to an acid-stable sulphoxidoenol ether . The sulphoxidoenol ether may be desulphurized with Raney nickel to the diene, or with lithium aluminium hydride reconverted to the thioenol ether for hydrolysis to the (x,j3-unsaturated ketone . These reactions are depicted in equation (80). 

Building on these results, Hanessian and co-workers devised an efficient protocol for the isomerisation of terminal olefins with minimal self-dimerisation or cross-metathesis by employing methanol to generate hydride complex 33 in situ from its parent 10. The procedure was successfully applied to a variety of allylic compounds, including O- and A-allyl ethers, and cleanly afforded the corresponding propenyl species as EjZ isomeric mixtures, without any further isomerisation or conjugation in the cases of ketones, esters and lactams. 

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