Saturated ketones, reduction

For enone to saturated ketone reductions, see page 13, Section 3.6. For stereochemistry of various reagents, see TL 34 6745 (1993)... 

For enone to saturated ketone reductions, see page 13, Section 3.6. 

All five Group I metals (Li, Na, K, Rb and Cs) and three Group II metals (Ca, Sr, Ba) have been used in NH3 to effect the reduction of ketones to secondary alcohols. " In addition, it has been reported that Yb-NH3 reduction of a,p-unsaturated ketones affords the saturated alcohol as the major product, which presumably arises via reduction of the intermediate saturated ketone.Reduction of (+)-camphor with Yb-NH3 both in the absence and presence of NH4CI affords the same 86 14 ratio of bomeol (2) to iso-bomeol (3). In the presence of NH4CI, the ketone is completely consumed and dimeric reduction products are not observed. Excess Yb-THF-HMPA effects bimolecular reduction of aromatic ketones, but aliphatic ketones are apparently inert to Yb-THF. - ... 

Me2C = CHCOCH= CMca- Yellow liquid having a camphor-like odour m.p. 28 C, b.p. 198-5°C. It is formed when propanone is saturated with HCl and allowed to stand. Resembles camphor in many of its properties and is a solvent for cellulose nitrate. Used to prepare diisobutyl ketone (reduction). 

The isophytol side chain can be synthesized from pseudoionone (Fig. 5) using chemistry similar to that used in the vitamin A synthesis (9). Hydrogenation of pseudoionone (20) yields hexahydropseudoionone (21) which can be reacted with a metal acetyUde to give the acetylenic alcohol (22). Rearrangement of the adduct of (22) with isopropenyknethyl ether yields, initially, the aHenic ketone (23) which is further transformed to the C g-ketone (24). After reduction of (24), the saturated ketone (25) is treated with a second mole of metal acetyUde. The acetylenic alcohol (26) formed is then partially hydrogenated to give isophytol (14). 

IV. REDUCTION OF CONJUGATED ENONES AND DIENONES, SATURATED KETONES AND KETOL ACETATES. 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Reduction of a conjugated enone to a saturated ketone requires the addition of two electrons and two protons. As in the case of the Birch reduction of aromatic compounds, the exact order of these additions has been the subject of study and speculation. Barton proposed that two electrons add initially giving a dicarbanion of the structure (49) which then is protonated rapidly at the / -position by ammonia, forming the enolate salt (50) of the saturated ketone. Stork later suggested that the radical-anion (51), a one electron... 

Eq. (4e)] is not reduced by metal-ammonia solutions so that the existence of this equilibrium cannot lead to further reduction of the saturated ketonic product only protonation on carbon can result in further reduction (see page 39). 

Reductions of unsaturated ketones and a-acetoxy ketones usually are effected with an excess of reducing agent. For optimum yields of saturated ketones, the intermediate enolate salt obviously must not become protonated while... 

A widely used procedure for the reduction of conjugated enones to saturated ketones is that of Bowers, Ringold and Denot, Procedure 5 (section V). Ether-dioxane (1 1) is used as the organic co-solvent and solid ammonium... 

For the reduction of conjugated enones to saturated alcohols, Procedure 5 (section V) may be modified by adding methanol in place of ammonium chloride a sufficient excess of lithium is present to effect reduction of the intermediate saturated ketone to the alcohol. Procedure 2 (section V) for effecting Birch reductions is also useful for reduction of conjugated enones to saturated alcohols. Thus, 17-ethyl-19-nortestosterone affords crude 17a-ethyl-5a-estrane-3) ,17) -diol of mp 174-181°, reported mp 181-183°, in quantitative yield. 

Epoxides are normally hydrogenated in preference to saturated ketones but double bonds are usually reduced under these conditions. It is possible in some cases to selectively cleave an epoxide without saturating double bonds by the use of the deactivated catalysts recommended for the partial reduction of acetylenes (see section IV) or by the addition of silver nitrate to the palladium-catalyzed reaction mixture. " ... 

There are ample precedents for reductions of double bonds in conjugated enones with lithium in deuterioammonia (see section V-C). Examples of the reduction of saturated ketones in deuterated media appear only as side reactions (over reductions) during the above mentioned conversions. For experimental details, therefore, one should consult the literature for the analogous reductions in protic medium (see also chapter 1). The use of deuterioammonia is essential for labeling purposes since by using liquid ammonia and methanol-OD the resulting alcohol contains no deuterium. For the preparation of deuterioammonia see section IX-D. 

J. E. StaiT, Metal Ammonia Reductions of Steroidal Enones, Saturated Ketones, and Ketols in Steroid Reactions, C. Djerassi, ed., Holden-Day, Inc., San Francisco, 1963, Chapter 7. 

Olefin formation by reduction of a,/3-un-saturated ketones with diborane, 347 Olefin formation by reductive eliminations, 343... 

The principal constituent of (he oil is a saturated ketone of the formula C],H,0. which is the active tariety of pino-camphone, which baa been prepar in the inactive form svutbettcally. bv Wallaob, by the reduction of nitrosopineue. The characters of thet -o bodies are as follows r -... 

The constitution of verbenone has been established by its reduction to the corresponding saturated secondary alcohol, dihydroverbenol, and into the corresponding saturated ketone, or dihydroverbenone. 

Reduction of carbon-carbon double bond Microalgae easily reduce carbon-carbon double bonds in enone. Usually, the reduction of carbonyl group and carbon-carbon double bond proceeds concomitantly to afford the mixture of corresponding saturated ketone, saturated alcohol, and unsaturated alcohol because a whole cell of microalgae has two types of reductases to reduce carbonyl and olefinic groups. The use of isolated reductase, which reduces carbon-carbon double bond chemoselectively, can produce saturated ketones selectively. 

The isomerisation of aUylic alcohols to saturated ketones usually has a strong thermodynamic driving force. The ruthenium NHC complex 62 has been used to catalyse the isomerisation of allylic alcohol 59 which gives ketone 60 as the principal product along with some of the reduction product 61 [32]. The catalyst was water-soluble and the aqueous phase could be re-used for several runs (Scheme 11.15). NHC analogues of Crabtree s catalyst, [IrlPCyjKpyridineXcod)] PFg, were found to be less efficient for the isomerisation of allylic alcohols than... 

Reduction of aryl diazonium ions by Ti(III) in the presence of a,(3-unsaturated ketones and aldehydes leads to (3-arylation and formation of the saturated ketone or aldehyde. The early steps in this reaction parallel the copper-catalyzed reaction. However, rather than being oxidized, the radical formed by the addition step is reduced by Ti(III).116... 

The PMHS, copper-catalyzed reduction of fi-substituted aq/l-unsaturated ketones to saturated ketones is accomplished in good yield with ee values in the 90 to 95% range when (S)-/ -Tol-BINAP is employed as the chiral ligand.595,596 Higher ee values are achievable with the use of a copper catalyst and (/ )-100 as the chiral ligand (Eq. 351).597... 

One or both carbonyls in /3-diketones can be reduced, as well as the carbonyl function in acyl cyanides (210). Similar treatment of a,/3-unsat-urated ketones and aldehydes can lead to the saturated carbonyl products via selective reduction of the olefinic bond (207, 208, 210) see Eq. (51) in Section III,A,4. Some terpenes (a- and /3-ionone, pulegone) were reduced in this way (208). Platinum(II) phosphine complexes have been used for the hydrosilylation of saturated ketones and could be used for the reduction (211). 

Rh(bpy)2]+, obtained by the in-situ reduction of [Rh(bpy)2Cl2]Cl with hydrogen in methanolic sodium hydroxide [43], can reduce a series of simple ketones under 1 bar H2 and at 30 °C [44]. Yields of over 98% were obtained in all cases with a SCR of up to 680 1. When a mixture of ketones and aldehydes was placed under such conditions, the ketones were found to be reduced preferentially, although unsaturated ketones were generally reduced to saturated ketones. 

As for some of the monodentate phosphine-based catalysts, ds-[Ru(6,6 -Cl2bpy)2(0H2)2][CF3S03]2 was found to require water for the best catalytic activity in the reduction of aldehydes and ketones [57]. Aldehydes and ketones were found to be hydrogenated, with reasonable yields. Unsaturated aldehydes were reduced with selectivity towards the unsaturated alcohol, whereas unsaturated ketones showed selectivity towards the saturated ketones. 

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