Alcohols diastereomeric mixture

In 2005, another class of chiral ligands, bis(thiazolines) derivatives, was prepared by Nishio et al. from chiral bis-(A-acylamino alcohols) by using Lawesson s reagent. These new compounds have proved to be useful chiral ligands for the Zn-catalysed Diels-Alder reaction of 3-acryloyloxazolidine-2-one with cyclopentadiene, giving the corresponding cycloadducts as a 94 6 diastereomeric mixture, where the major diastereomer was formed with 92% ee (Scheme 5.14). 

In 12 the upper face is shielded by the isopropyl group, whereas in 13 the lower face is shielded by the methyl and phenyl groups. As a result, alkylation of the two derivatives gives products of the opposite configuration. The initial alkylation product ratios are typically 95 5 in favor of the major isomer. Since these products are diastereomeric mixtures, they can be separated and purified. Subsequent hydrolysis or alcoholysis provides acids or esters in enantiomerically enriched form. Alternatively, the acyl imides can be reduced to alcohols or aldehydes. The final products can often be obtained in greater than 99% enantiomeric purity. 

The use of trichloroimidates for the preparation of ethers is an effective method for O-alkylation of alcohols [27]. This method has found widespread use in the protection of alcohols as benzyl ethers since the corresponding trichlorobenzylimi-date is inexpensive and commercially available. The mechanism involves activation of the imidate with a catalytic amount of a strong acid (typically TfOH) which leads to ionization of the electrophile and the formation of carbocation which is rapidly trapped by an alcohol. For the preparation of sec-sec ethers, this protocol has been limited to glycosidation reactions, due to the SN1 nature of the reaction which often leads to diastereomeric mixtures of products [26],... 

In another approach, the alcohol moiety, formed by an enzymatic hydrolysis of an ester, can act as a nucleophile. In their synthesis of pityol (8-37a), a pheromone of the elm bark beetle, Faber and coworkers [17] used an enzyme-triggered reaction of the diastereomeric mixture of ( )-epoxy ester 8-35 employing an immobilized enzyme preparation (Novo SP 409) or whole lyophilized cells of Rhodococcus erythro-polis NCIMB 11540 (Scheme 8.9). As an intermediate, the enantiopure alcohol 8-36 is formed via kinetic resolution as a mixture ofdiastereomers, which leads to the diastereomeric THF derivatives pityol (8-37a) and 8-37b as a separable mixture with a... 

Cycloadduct 30a underwent an easy cleavage of the sulfur-carbon bond by attack of alcohols to give ring-opening products 31 and 32, the latter as inseparable diastereomeric mixtures (see Equation (6) and Table 3) <1997T4611>. A completely regioselective reaction was observed with bulky alcohols resulting in the exclusive formation of 31 (see entries 3 and 4). 

Like Still s reagent, tributyl[(methoxymethoxy)methyl)etannane incorporates an alcohol protective group that can be conveniently unmasked under mild acidic conditions. However, an advantageous feature of this MOM ether derivative is that, in contrast to Still s reagent, it is achiral. In many applications the introduction of an additional chiral center into synthetic intermediates is undesirable because of the complications associated with the manipulation, analysis, and purification of diastereomeric mixtures. 

The secondary hydroxyl group of 206 is now protected with a PMB group. Reduction of the resulting diastereomeric mixture 207 gives the corresponding alcohol 208, which is then separated to give a single stereoisomer. A silyl ether... 

When the diazoimides 253 are subjected to Rh2(OAc)4 at 80 °C in presence of an alkyl alcohol, pcrhydropyrrolo[2,1 -b -oxazol-4-ones 254 were isolated in good yields as a diastereomeric mixture. If the alcohol is replaced by terminal alkyl diols, the corresponding bis(2,3-fused perhydropyrrolo[2,l- ]oxazol-4-one) systems 255 were obtained (Scheme 37) <2003CC440>. 

As depicted in Fig. 6, syntheses of enantiomerically pure 116 and 117 have been carried out [236]. Lipase AK-catalysed asymmetric acetylation of meso-2,4-dimethyl-1,5-pentanediol A yielded (2R,4S)-5-acetoxy-2,4-dimethylpen-tanol B. Protection of the free hydroxy group as the terf-butyldimethylsilyl (TBS) ether, saponification of the acetate, and oxidation furnished the aldehyde C. Reaction of C with ethylmagnesium bromide gave a diastereomeric mixture of the corresponding secondary alcohols which could be resolved by asym-... 

More recently, using the cyclometallated iridium C,(7-benzoate derived from allyl acetate, 4-methoxy-3-nitrobenzoic acid and BIPHEP, catalytic carbonyl crotylation employing 1,3-butadiene from the aldehyde, or alcohol oxidation was achieved under transfer hydrogenation conditions [274]. Carbonyl addition occurs with roughly equal facility from the alcohol or aldehyde oxidation level. However, products are obtained as diastereomeric mixtures. Stereoselective variants of these processes are under development. It should be noted that under the conditions of ruthenium-catalyzed transfer hydrogenation, conjugated dienes, including butadiene, couple to alcohols or aldehydes to provide either products of carbonyl crotylation or p,y-enones (Scheme 16) [275, 276]. 

These observations were applied by Dimitrov, Hesse and coworkers. On stndying ozonization of a series of allylic and homoallylic alcohols prepared from (+) camphor and (—) fenchone, they were able to isolate a certain number of ozonides and to obtain the O NMR spectrum of the diastereomeric mixture of one of them, i.e. derivative 15, whose structure and O NMR chemical shifts (5, ppm) are shown below. 

Further transformations of a-alkyl-3-oxazolidineacetonitriles are possible. Addition of methyllithium to the cyano group followed by acid hydrolysis gave a morpholine derivative, from which a /i-amino alcohol was obtained as a diastereomeric mixture (d.r. 80 20)69. 

This section deals with examples in which the enolate 2 from the ester 1 of a chiral, nonracemic alcohol R OH is alkylated to give the diastereomeric mixture 3 and 4. The measure of diastereoselectivity is the ratio of 3/4. 

The chiral, nonracemic bicyclic lactams, used as starting materials for stereoselective alkylation reactions, are usually prepared by treating a mixture of the enantiomerically pure vicinal amino alcohol 1 with a 3-acylpropanoic or 4-acylbutanoic acid 2 (R4 = H) under acid catalysis in toluene with azeotropic removal of the resulting water1-17. When formation of the bicyclic aminal is complete, it is isolated as a diastereomeric mixture which is usually easy to purify and provides the major diastereomer 3. An alternative method for preparation of the bicyclic lactam uses the same conditions with a 2-substituted acid (R4 =1= H). This leads to a roughly 50 50 mixture of diastereomers 3 and 4 which can be used directly for the next step2,5,12. 

Fluorodehydroxylation of the diastcrcomeric benzylic amino alcohols, r/-cphedrine and pseudoephedrine affords, in 100% yield, the same 2 1 diastereomeric mixture of 2-fluoro-/V,l-dimcthyl-2-phenylethylamines (2). This, and also exclusive formation of 4-fluoropiperidine from both piperidin-3- and -4-ol, implies participation of stable carbeninm ion precursors.40... 

Elaboration of 2-isoxazolines via their 4-endo-anions has been studied as a method to synthesize y-amino alcohols (78TL3129,3133,81AG(E)601,603). When the 5-methyl-3-phenyl-2-isoxazoline (527) was deprotonated with LDA/HMPA and methylated with methyl iodide, the tra 5-4,5-substituted isoxazoline (528) was formed predominantly (trans-.cis = 12 1). Reduction of this isoxazoline with lithium aluminum hydride proceeded with steric approach control to provide a diastereomeric mixture of y-amino alcohols (529, 530 Scheme 116). The 5-substituent was found to exhibit a greater steric influence on this reaction than the 4-substituent. 

An asymmetric synthesis of mevalolactone in over 87% e.e. employs a 1,3-oxathiane as the chiral auxiliary (81TL2859). The reagent (818), easily prepared from (+)-pulegone (81TL2855), was metallated with u-butyllithium and the anion reacted with acetaldehyde. Oxidation of the diastereomeric mixture of alcohols to the ketone (819) and reaction of... 

I-Allenyl dienes. Reaction of C6H5SCI with the propargyl alcohol 1 results in the ilrimatriene derivative 2 (as a diastereomeric mixture), formed by spontaneous cycli/alion of the allenyldiene a. The triene 2 undergoes an unusual 1,6-reduction when treated with excess lithium aluminum hydride to give a (rara-decalin (3) in 70% yield,1... 

The initial a-addition adduct from the reaction of methyl (S)-2-isocyano-4-methylpentanoate 232 and protected (S)-alaninal 233 further reacted with benzoic acid to furnish 234 as a diastereomeric mixture. The stereochemistry of the resulting benzoyl-protected alcohol was inconsequent since the latter functionality is oxidized during the course of the synthesis using pyridinium dichromate to afford the a-oxoamide in the final target. In general, however, in isocyanide MCRs the control of the newly created stereogenic center is problematic and separation of diastereomeric mixtures cannot be avoided. A recent report by Denmark and Fan on a catalytic asymmetric variant of this reaction therefore represents an interesting development [119]. 

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