A-deuterio alcohol

Reaction of saturated acylzirconocene chlorides with (CH3)2Cu(CN)Li2 gives the secondary alcohol (73%), and D20 work-up of the reaction mixture gives the a-deuterio alcohol. This observation suggests the formation of a ketone—zirconocene complex (Scheme 5.40 see also Section 5.3.2.1). Thus, for the reaction of a,p-unsaturated acylzirconocene chlorides with R2Cu(CN)Li2, initial formation of an unsaturated ketone—zirconocene complex followed by 1,3-rearrangement of the zirconocene moiety to an oxazirconacyclopentene, which is a ketone carbanion equivalent, has been proposed (Scheme 5.41). 

Deuteration can generally be carried out by reaction of D20 or a deuterio-alcohol (e.g. CH3OD or r-BuOD) with the organometallic intermediate. 

The high price of the deuteration reagents requires their economical use. However, stoichiometric amounts often give incomplete conversions. Although deuterations are extremely fast, the hydroxide or alkoxide R OM form complexes with R OD from which D is less readily available. Therefore, at least 100% excess of R OD should be used. If the deuteration has to be carried out at low temperatures, D20, if added to the reaction mixture, solidifies, so that complete deuteration may not be achieved hence, use of a deuterio-alcohol (THF or Et20 solution) is preferred. 

ESTERIFICATION OF HINDERED ALCOHOLS tert-BUTYL p-TOLUATE, 51, 96 Esters, from diazoketones and organoboranes, 53, 82 Esters, a-deuterio-, 53, 82 Esters, y [Pg.59]

This interpretation was proved correct by considering the oxidation of a sample of diphenylmethane that had an isotopic purity of 97.0% a,a-dideuterio and 2.7% a-deuterio by mass spectrometry. The oxidation rate observed after the initial 15-second period (see Figure 2), during which the undeuterated and monodeuterated material were destroyed, yielded a second-order rate constant, ki = 0.0148 mole"1 per second. There is thus an appreciable isotope effect ku/kD of about 6 in the ionization of diphenylmethane by potassium ferf-butoxide in DMSO(80%)-tert-butyl alcohol (20% ) at 25°C. This compares with a value of fcH/ D of 9.5 reported for the ionization of triphenylmethane (16). The observation of primary isotope effects of this magnitude requires that the protonation of the diphenylmethide ion by tert-butyl alcohol in DMSO solution does not proceed at the diffusion rate which would, by the principle of microscopic reversibility, require the absence of an isotope effect in the deprotonation step. 

R,R)-TsDPEN-RuCl(p-cymene) complex catalyzes the deuteration of benzalde-hydes by using only a stoichiometric amount of the deuterium source, DCOOD/ N(C2Hs)3, to give the S deuterio alcohols in up to 99% e.e. [285]. The dj content in... 

A number of experimental details have contributed to an understanding of the mechanism of reductions carried out under these conditions. Among the more important observations are the facts that ketones react with one and only one equivalent of alkali metal in NH3 enolizable ketones afford equal amounts of enolate and alcohol, while nonenolizable ketones give metal ketyls which are stable at low temperatuie. Also, pinacol formation is a major reaction path with Li, but K affords little or no pina-col. - Finally, a-deuterio ketones afford product alcohols in which deuterium has been transferred to the carbinol carbon of the product alcohol or alcohols. - ... 

A hydride shift is invoked to explain deuterium distribution among the products when the 3-tosylate (127) of cholest-5-ene-3)9,4)S-diol is reduced with lithium aluminium deuteride.In this first identification of all three main products from a reaction first described in 1951, 4) -deuteriocholest-5-en-4a-ol (129) is considered to arise from reduction of the 5-en-4-one (128), formed by a hydride shift (4a — 3a marked a) as illustrated. Sodium hydride promoted the same rearrangement to give the 5-en-4-one (128). The 3 -deuterio-A-nor-alcohol... 

Evidence for this postulate was provided by epimerization of deuterio-or tritio-labeled derivatives of (148) 117). As the result, a retro-aldol type mechanism in which stereoelectronic requirements are satisfied in the transition state was suggested. The process is depicted in Figure 5. This concept was also applied to the retro-Dieckmann type cleavage of ketone (151) to carboxylic acid (152) (Scheme 31), the facile epimerization of the 3p-axial alcohol (153) to the 3 a-equatorial alcohol (154) under the influence of dilute alkali (followed by esterification) and the cleavage of the 3-ketone (155) to methyl ester (156) on treatment with sodium hydroxide in methanol at 0°C for one hour (Scheme 31). 

Consequently, a deuterated B-3-pinanyl-9-BBN finds applications in the reduction of variety of aromatic, aliphatic, and a,p-unsaturated aldehydes to the corresponding chiral primary 1-deuterio alcohols either with (R)- or (S)-con-figuration. 

The isotopic purity of the product is usually about 48-62%, the rest of the material being mainly undeuterated. (An alternate preparation of a-mono-deuterio ketones of high configurational and isotopic purity is the mild oxidation of cis- or tra 5-deuterated alcohols under Jones conditions, see sections V-D and VII-A.) Treatment with zinc in acetic acid-OD has also been applied to the deiodination of 2a-iodoandrost-4-ene-3,17-dione. In a slightly modified version the iodine in 19-iodocholesterol acetate has been replaced with tritium by using tritium oxide as the isotope source/... 

The reduction of different aliphatic or aromatic aldehydes or ketones 15 was easily achieved using the combination of dihydrated nickel(II) chloride, lithium and a catalytic amount of naphthalene (16%) or DTBB (8%) in THF, yielding the corresponding alcohols without (534) or with (535) deuterium labelling in 57-86% yield. For imines 536, the same process afforded the corresponding amines 537 or deuterio amines 538 in 54- >95% yield . 

Berkessel and Sklorz screened a variety of potential co-ligands for the Mn-tmtacn/H202 catalyzed epoxidation reaction and found that ascorbic acid was the most efficient one. With this activator the authors could oxidize the terminal olefins 1-octene and methyl acrylate with full conversion and yields of 83% and 97%, respectively, employing less than 0.1% of the metal complex (Scheme 86). Furthermore, with E- and Z-l-deuterio-1-octene as substrates, it was shown that the oxygen transfer proceeded stereoselectively with almost complete retention of configuration (94 2%). Besides the epoxidation, also the oxidation of alcohols to carbonyl compounds could be catalyzed by this catalytic system (see also Section in.C). 

In the second step, achiral 9-borabicyclo[3.3.1]nonane (9-BBN) adds to the less hindered diastereotopic face of a-pinene to yield the chiral reducing agent Alpine-Borane. Aldehydes are rapidly reduced to alcohols. The reaction with deuterio-Alpine-Borane, which yields (R)-a-d-henzy alcohol in 98% enantiomeric excess ( ) reveals a very high degree of selectivity of the enantiotopic faces of the aldehyde group in a crowded transition state ... 

Of the numerous nicotinamide model studies done since about 1970, the one that had perhaps the greatest impact on mechanistic thinking revealed a discrepancy between the kinetic deuterium isotope effect and the H/D ratio in the alcohol product formed upon reduction of trifluoroacetophenone by 4-protio- and 4-deuterio-A-alkyl-l,4-dihy-dronicotinamides (Scheme 2) (71JA6694). For example, while the reduction of... 

When ethanol is oxidized by the action of alcohol dehydrogenase (Eq. 9-73), only the pro-R hydrogen atom is removed. If the reaction is reversed in such a way that deuterium is introduced into ethanol from the reduced coenzyme the optically active R-2-deuterio-ethanol is formed. The ability of an enzyme to... 

Midland, M. M., Greer, S., Tramontane, A., Zderic, S. A. Chiral trialkylborane reducing agents. Preparation of 1-deuterio primary alcohols of high enantiomeric purity. J. Am. Chem. Soc. 1979, 101, 2352-2355. 

Asymmetric reduction of a,fi-acetylenic ketones. This borane can be used to reduce 1-deuterio aldehydes to chiral (S)-l-deuterio primary alcohols in 90% optical yields. It also reduces a, -acetylenic ketones to (R)-propargylic alcohols with enantiomeric purity of 73-100%. The ee value is increased by an increase in the size of the group attached to the carbonyl group. The value is also higher in reductions of terminal ynones. Alcohols of the opposite configuration can be obtained with the reagent prepared from (—)-a-pinene. 

Deuterium isotope effects on chemical shifts of phenols of which the OH proton has been exchanged by deuterium can be measured in two different ways. If the OH(D) proton is exchanging slowly (see Section II.B) two different resonances are observed, one due to the protio and one due to the deuterio species (see Figure 1). The relative intensities will depend on the H D ratio, perhaps not in a quantitative way due to fractionation (see Section II.O). If exchange is fast on the NMR time scale only one resonance for the X-nuclei (e.g. C) is observed, the position of which depends on the H D ratio. In order to determine the isotope effects properly, a series of experiments must be conducted varying the H D ratios of the exchanging species, typically 1 5, 1 2, 1 1, 2 1 and pure solvent . The exchanging species is typically H2O D2O but could equally well be deuteriated alcohols, ROD. 

Scheme 28 illustrates the asymmetric hydrogenation of 1-deuterio 0-bromoben-zaldehyde catalyzed by an (R)-BINAP-Ru complex and 5 equiv of HCl giving a 1-deuteriobenzyl alcohol in 89% ee [86]. The bromine atom at the oposition tends to increase the enantioselectivity through its interaction with the metal center of the catalyst. Deuteration of benzaldehyde with this catalyst occurs much more slowely. 

The trans-bromohydrin (125) is reduced directly by nucleophilic displacement of the bromo-substituent, lithium aluminium deuteride giving the 16a-mono-deuterio-17a-alcohol (126). The near-planar conformation of the five-membered ring is unfavourable to epoxide formation, observed under similar conditions in a six-membered ring. ... 

Reduction of (14b) with sodium borodeuteride in 0-deuterio- or 0-deuterioiso-propyl alcohol led to a 97 % monodeuteriated rearranged product in which 80% of the deuterium was incorporated at position 18. 

NADH or aldehyde) in excess of the other reactant. Under these conditions, the chemical conversion of aldehyde to alcohol occurs with a (saturated) apparent first-order rate constant of 200 to 400 sec i. This process, as measured either by the disappearance of NADH or by the disappearance of chromophoric aldehyde, has been shown by McFarland and Bernhard (80) to be subject to a primary, kinetic isotope effect ksjkj) =2 to 3 when stereospecifically labeled (4-R)-deuterio NADH is compared to isotopically normal NADH. Shore and Gutfreund (84) earlier had investigated substrate kinetic isotope effects on the pre-steady-state phase of ethanol oxidation. Their studies demonstrated that the rate of the presteady-state burst production of NADH is subject to a primary kinetic isotope effect, kulkj) 4—6 when 1,1-dideuterio ethanol is compared to isotopically normal ethanol, and that there is no primary kinetic isotope effect on the steady-state rate. It can be concluded from these studies (a) that the rate of interconversion of ternary complexes e.g., Eq. (19) above], as already mentioned, is rapid relative to turnover, and (b) that the transition-state for the rate-limiting step in the interconversion of ternary complexes involves carbon-hydrogen bond scission and/or carbon-hydrogen bond formation. 

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