Ethers ketone reduction gives

A mixture of the ketone (4.62 g), iridium tetrachloride (1.23 g), trimethyl phosphite (15 ml), propan-2-oI (200 ml) and water (50 ml) is heated under reflux for 21 hr. Much of the solvent is then distilled off ca. 215 ml) and the organic products remaining are isolated by extraction with ether. If reduction is essentially complete, the product at this stage may be sufficiently pure for most preparative purposes. Pure components can be obtained by chromatography over alumina, a representative experiment (on the above scale) gives unchanged ketone (0.13 g), cw-alcohol (4.36 g) and tmns-2 co o (0.16 g) (eluted in this order by pentane, and then by pentane containing ether). 

Even more highly selective ketone reductions are earned out with baker s yeast [61, 62] (equations 50 and 51) Chiral dihydronicotinamides give carbonyl reductions of high enantioselectivity [63] (equation 52), and a crown ether containing a chiral 1,4-dihydropyridine moiety is also effective [64] (equation 52). 

The reaction processes shown in Scheme 8 not only accomplish the construction of an oxepane system but also furnish a valuable keto function. The realization that this function could, in an appropriate setting, be used to achieve the annulation of the second oxepane ring led to the development of a new strategy for the synthesis of cyclic ethers the reductive cyclization of hydroxy ketones (see Schemes 9 and 10).23 The development of this strategy was inspired by the elegant work of Olah 24 the scenario depicted in Scheme 9 captures its key features. It was anticipated that activation of the Lewis-basic keto function in 43 with a Lewis acid, perhaps trimethylsilyl triflate, would induce nucleophilic attack by the proximal hydroxyl group to give an intermediate of the type 44. 

Reductive Etherification. As indicated earlier, aldehydes as well as ketones often give very good yields of ethers when they are treated with Br0nsted acids or other electrophilic species in the presence of organosilicon hydrides (Eq. 172). In the absence of added alcohols, symmetrical ethers are obtained. 

Like their sulfur counterparts (Section 3.2.4.4.2.), 1 -lithiocyclopropyl selenides 1, as generated by reductive lithiation of bis(selanyl)cyclopropanes 173 with butyllithium in diethyl ether or tetrahydrofuran, react with aldehydes or ketones to give /Lhydroxy selenides 2, which rearrange to cyclobutanones 3 on treatment with p-toluenesulfonic acid in wet benzene.174 175 The method was used in a total synthesis of a-cuparenone.175... 

The phenols need to be protected as their methyl ethers 67 and functionalisation by SeC>2, as described earlier in this chapter, gives the keto-aldehyde 68. To get 65 we should have to reduce the ketone in the presence of the aldehyde but the workers at Boehringer discovered a shortcut reductive amination using hydrogenation reduced both the imine (from i-PrNH2 and the aldehyde) and the ketone to give 69 and hence, by deprotection, metaproterenol 64. Notice that the aldehyde in 68 is more electrophilic than the conjugated ketone so it forms the imine needed for reductive amination. 

In contrast with the common activity of oxo-rhenium compounds in oxidation catalysis (see above), the Re -dioxo-complex [Re02l(PPh3)2] catalyzes the reductive hydrosilylation of aldehydes and ketones to give silyl ethers (reaction... 

Reductive nucleophilic acylation. The reagent 1 condenses with aldehydes and ketones to give products (2) of carbonyl addition, which do not undergo syn-elimination of —OSi(CH3)3 in situ. However, treatment of 2 with KH in THF affords enol ethers (3) in excellent yields. The latter products are readily converted into aldehydes (4) on hydrol) is with 90% aqueous formic acid ( 90% yield, equation I). The adducts (2) are desilylated to 5 with CsF in DMSO (equation II). In this case, 1 functions as an equivalent of the —CH2OCH3 anion. 

I Birch reduction gives the enol ether of the ketone and demands careful hydrolysis to avoid... 

Transformation of 417b into lactone 419, followed by Mc2CuLi addition, hydroxylation, and oxidation with N-chlorosuccinimide gives the hydroxy lactone 420 (80JOC4820). Enol ether formation, reduction of the lactone and ester functions, and hydrolysis of the enol ether give hydroxy ketone... 

Anions from the Schiffs base (78) can be C- or A -alkylated with ethyl iodide or diethyl sulphate. The ratio of the products depends both on the solvent and on the presence of 18-crown-6. In non-polar solvents, the crown ether increases the solubility of the base, and C-alkylation is the major pathway. In dipolar aprotic solvents, the 18-crown-6 breaks up ion pairs by solvation of the Na" cation, and favours A -alkylation. A nerylsulphonamide, formed from (79), undergoes regiospecific reductive desulphonylation to give nerol (80), which implies that (79) is an effective synthon for cisoid iso-prenoids. Chiral complexes of crown ethers, e.g. (81), catalyse the Michael addition reaction of j3-keto-esters and methyl vinyl ketone to give adducts in high optical yields. ... 

The Birch reduction gives the enol ether of the ketone and demands mreful hydrolysis to avoid the alkene moving into conjugation with the etone. The aldol reaction requires some kind of control—perhaps the silyl enol ether of acetone will do. Now we need a reagent for CHO that will do conjugate addition. The most obvious choices are cyanide ion or nitromethane. The last step is the same as in the first synthesis. 

The reactivity of alkyllithiums towards ketones and thioketones has been investigated. " Whereas alkyllithiums add to the carbonyl carbon of ketones to give tertiary alcohols, the reaction with thioketones proceeds to give secondary thiols by reduction of the C=S group. Transition states for such addition and reduction reactions of acetone and thioacetone in ethereal solution have been located and the computed activation free energies are in agreement with experimental results. 

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