Selectivity of reduction

Two factors of paramount importance in understanding the chemistry of metal-ammonia reductions are the acidity of the reaction medium and the relative rates of all reactions possible with a given combination of reagents. The control or appreciation of these factors permits one to achieve a certain degree of selectivity in metal-ammonia reductions in spite of the vigor of the reducing agents. 

The reduction of a benzenoid ring, except in benzoic acid derivatives, occurs only in the presence of a proton donor having a pKa of 19 or less (pKa of ammonia is about 33). With the exception of the vinyl group, the other functional groups listed above do not require a proton donor of this acidity in order to be reduced, although the course of reduction may then be complex, e.g. as with esters. Consequently, a variety of functional groups should be capable of selective reduction in the presence of a benzenoid ring if the reaction medium does not contain an acid of pKa 19. A few examples of such selective reductions have been reported in the steroid literature. 

The styrene double bond in 9(ll)-dehydroestradiol 3-methyI ether (1) or its 8-dehydro counterpart is reduced by potassium or lithium in ammonia without affecting the aromatic ring estradiol 3-methyl ether (2) is formed from both compounds. Reduction of the corresponding 17-ketones occurs with partial or complete reduction of the carbonyl group. Lithium 

Certain functional groups may be protected from reduction by conversion to anions that resist reduction. Such anions include the alkoxides of allylic and benzylic alcohols, phenoxide ions, mercaptide ions, acetylide ions, ketone carbanions, and carboxylate ions. Except for the carboxylate, phenoxide, and mercaptide ions, these anions are sufficiently basic to be proton-ated by an alcohol, so they are useful for protective purposes only in the 

Treatment of the 9-fiuoro-l,4-dien-3-ol (15) with 3.5 g-atoms of lithium and l-methoxy-2-propanol in ammonia reductively cleaves the allylic 3-hydroxyl group to give t7 corresponding 3-desoxy compound, but the fluorine 

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In pyridine, as in 2-propanol, the selectivity of reduction favors the A" -3-ketone over the 17- and 20-ketones.Kupfer suggests that resonance interactions between the double bond and the 3-ketone are smaller in pyridine and in 2-propanol than in methanol. However, by slow addition (1 hour) of one equivalent of NaBH4 in pyridine to a solution of androst-4-ene-3,17-dione i n methanol, testosterone has been obtained in good yield (72 %). Similarly,... 

Both amine oxides related to pyridines and aliphatic amine oxides (/25) are easily reduced, the former the more so. Pyridine N-oxide has been reduced over palladium, platinum, rhodium, and ruthenium. The most active was rhodium, but it was nonselective, reducing the ring as well. Palladium is usually the preferred catalyst for this type of reduction and is used by most workers 16,23,84 158) platinum is also effective 100,166,169). Katritzky and Monrol - ) examined carefully the selectivity of reduction over palladium of a... 

Scheme 31 Scope and selectivity of reductive enyne cyclization by Rh4(CO)i2...

FIGURE 22.4. Decision tree for selection of reduction of dimensionality procedures. 

Allenes are reduced in two distinct stages. In the first stage, the major products are olefins, accompanied by a small amount of the alkane, while in the second stage the olefins produced are reduced to alkanes. The selectivity of reduction varies with the metal34, and for allene itself at various temperatures it decreased in the following series of metals ... 

Species 111 formed by trans-addition of e.g. ClCHj—Cl to Pt(II)d metallacyclopentanes show the effect of hgand constraint on the selectivity of reductive elimination. Complexes in which L is a monodentate phosphine decompose preferentially... 

The main methods of reducing ketones to alcohols are (a) use of complex metal hydrides (b) use of alkali metals in alcohols or liquid ammonia or amines 221 (c) catalytic hydrogenation 14,217 (d) Meerwein-Ponndorf reduction.169,249 The reduction of organic compounds by complex metal hydrides, first reported in 1947,174 is a widely used technique. This chapter reviews first the main metal hydride reagents, their reactivities towards various functional groups and the conditions under which they are used to reduce ketones. The reduction of ketones by hydrides is then discussed under the headings of mechanism and stereochemistry, reduction of unsaturated ketones, and stereochemistry and selectivity of reduction of steroidal ketones. Finally reductions with the mixed hydride reagent of lithium aluminum hydride and aluminum chloride, with diborane and with iridium complexes, are briefly described. 

Figure /. Time dependence of the selectivities of reduction products upon reaction of nitrobenzene at a-Mn304 (575K).

Tab. 6.1 Selection of reduction potentials that are of interest in AOPs (data taken from Ward-man, 1989)...

Molecular orbital calculations have suggested that cyclopentenone is intrinsically more x one to conjugate reduction than cyclohexenone " and thus is a good substrate on which to test new 1,2-selective reagents. The selectivity of reduction of both these enones with the best of the new reagents together with the results for 9-BBN-H, the previous reagent of choice, are tabulated for comparison (Table 2). 

A pulsed electrolysis of COj on Au, Ag and Cu and their alloyed electrodes was performed, laying special emphasis on an improvement of the selectivity of reduction products. The effect of anions (Cl, Br, I ) intentionally added to a KHCO3 blank solution on the selectivity was investigated. The pulsed electrolysis was found to have a remarkable effect in enhancing hydrocarbonization reactions on Ag and Cu, while little on Au. It is concluded that oxide surface formed during an anodic period may play a key role in the selectivity of reduction products of COj. 

Selective catalytic hydrogenation of the 6,7-double bond of 17/3-acetoxy-7-methylandrosta-4,6-dien-3-one was achieved with Pd-C-PhCH20H and gave the 7/8-methyl dihydro-compound. Added FeCls has been reported to improve the selectivity of reduction of a,/S-enones in metal-ammonia reactions, thereby improving the yield of the saturated ketones. Similar improvements were observed in the lithium-ethylamine reductions at -78 C when a substantial excess of lithium was used and t-butyl alcohol was the proton source. The influence of solvent and added nitrogenous bases on the stereoselectivity of hydrogenation of A - and A -3-oxo-steroids with Pd catalysts has been studied, and the stereoselectivity of Pd-catalysed hydrogenation of various A -7-oxo-steroids has been reported to be unaffected by substituents at C-3 or C-17. 

In this expression, Ej° is the standard electrode potential, i.e., the value of Ej when the activities of both the reduced and oxidized forms are unity. Tables of E° values (see Appendix) are useful for the selection of reductants of suitable strength. It will be noticed that for redox couples having positive E° values, the oxidized form is superior to the hydrogen ion as an oxidant. The more effective reducing agents are the reduced forms of couples having negative E° values. 

Some finer effects caused by additives were reported. Thus, the use of the pair rt-Bu4NOAc-KCl was used to control the selectivity of reductive elimination in the ary-lation of acrolein acetals (Scheme 2.7). Interestingly, a more usual reverse combination KOAc- -Bu4NC1 gave worse results with respect to selectivity [54, 55], which clearly shows that the Mizoroki-Heck reaction is often extremely sensitive towards subtle details of formulation of the catalytic system. As proposed by Cacchi and coworkers [54,68] for the -Bu4NOAc-KC1 cocktail [55-57], the coordination sphere of palladium is saturated to form an anionic complex 28 (28 29 + 30), in which palladium is not capable of coordinating to the aryl tt-system as in 31 (31 30, Scheme 2.7). 

It was shown that the selectivity of reduction changed from (S) selectivity with small chain esters to (R) selectivity with long chain esters. ... 

The selectivity of reduction is also illustrated by the observation that... 

Figure 1.20 Hydrophobic binding of a reagent to a substrate in water reverses the selectivity of reduction of a diketone.

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