Chiral alcohols, formation

Selenski investigated the use of chiral enol ether auxiliaries in order to adapt method F-H for enantioselective syntheses. After surveying a variety of substituted and unsubstituted enol ethers derived from a vast assortment of readily available chiral alcohols, she chose to employ enol ethers derived from trans-1,2-phenylcyclohexanol such as 73 and 74 (Fig. 4.37). These derivatives were found to undergo highly diastereoselective cycloadditions resulting in the formation of 75 and 76 in respective... 

When enzymes like alcohol dehydrogenase, are chiral, reduce carbonyl groups using coenzyme NADH, they discriminate between the two faces of the trigonal planar carbonyl substrate, such that a predominance of one of the two possible stereoisomeric forms of the tetrahedral product results, i) If the original reactant was chiral, the formation of the new stereocenter may result in preferential formation of one diastereomer of the product => a diastereoselectiv reaction. 

It is important to note that the Ru-catalyzed RCM and the Zr-catalyzed resolution can be carried out in a single vessel, without recourse to intermediate isolation. The unsaturated medium-ring amides 5 and 8 can be subjected to 10 mol% of the chiral Zr catalyst and EtMgCl, in the same flask, to afford unsaturated 6 and 9 in 81% and 54% isolated yield, respectively. As depicted in Eq. 1, a similar tandem diene metathesis/ethylmagnesation can be carried out on ether 10, leading to the formation of unsaturated chiral alcohol 11 in 73% yield and >99% ee. 

Chiral active pharmaceutical ingredients, 18 725-726. See also Enantio- entries Chiral additives, 6 75—79 Chiral alcohols, synthesis of, 13 667-668 P-Chiral alcohols, synthesis of, 13 669 Chiral alkanes, synthesis of, 13 668-669 Chiral alkenes, synthesis of, 13 668—669 Chiral alkoxides, 26 929 Chiral alkynes, synthesis of, 13 668-669 Chiral ammonium ions, enantiomer recognition properties for, 16 790 Chiral ansa-metallocenes, 16 90 Chiral auxiliaries, in oxazolidinone formation, 17 738—739... 

Surface modification of skeletal nickel with tartaric acid produced catalysts capable of enantiose-lective hydrogenation [85-89], The modification was carried out after the formation of the skeletal nickel catalyst and involved adsorption of tartaric acid on the surface of the nickel. Reaction conditions strongly influenced the enantioselectivity of the catalyst. Both Ni° and Ni2+ have been detected on the modified surface [89]. This technique has already been expanded to other modified skeletal catalysts for example, modification with oxazaborolidine compounds for reduction of ketones to chiral alcohols [90],... 

As the integrity of chiral alcohols are retained in the phase-transfer catalysed O-alkylation, the procedure is valuable for the synthesis of chiral ethers under mild conditions as, for example, in the preparation of alkoxyallenes via the initial formation of chiral propargyl ethers [8]. It has been proposed that a combination of 18-crown-6 and tetra-n-butylammonium iodide provide the best conditions for the O-benzylation of diethyl tartrate with 99% retention of optical purity [9]. 

As a consequence of the wide choice of hydride reagents the classical methods such as reduction with sodium in ethanol almost fell into oblivion [579, 520]. Nevertheless some old reductions were resuscitated. Sodium di-thionite was found to be an effective reducing agent [262], and the reduction by alcohols [309] was modified to cut down on the temperature [755] or the time required [527], or to furnish chiral alcohols ( in good yields and excellent optical purity ) by using optically active pentyl alcohol and its aluminum salt [522]. Formation of chiral alcohols by reduction of pro-chiral ketones is... 

The hydrodimerization of cinnamate esters formed with a chiral alcohol leads to asymmetric induction at the carbon-carbon bond formation step. The ester with bomeol gives a chiral cyclopentanone with greater than 95% enantiomeric excess [55]. A second approach towards achieving a chiral carbon-carbon bond formation has been to use the asymmetric oxazolidones 15 as substrates. These are reduced at... 

The formation of chiral alcohols from carbonyl compounds has been fairly widely studied by reactions of aldehydes or ketones with organometallic reagents in the presence of chiral ligands. Mukaiyama et al. 1081 obtained excellent results (up to 94% e.e.) in at least stoichiometric addition of the chiral auxiliary to the carbonyl substrate and the organometallic reagent. 

In this case both enantiomers 3 and ent-3 react with Pd(0)/BPA with formation of the two diastereomeric 7c-allyl-Pd( II) complexes 25 and 26, respectively (Scheme 2.1.4.29). Only if the following conditions exist can the racemic substrate be completely converted to the chiral alcohol with high efficiency 1) the reactivity of the 7c-allyl-Pd(II) complexes 25 and 26 must be different 2) a fast diastereom-erization of 25 and 26 or racemization of 3 and/or ent-3 must take place 3) BPA must induce a high stereoselectivity 4) the substituents of the allylic substrate have to provide for a high regioselectivity [39]. 

After characterization of the systems, biotra ns formations were performed to produce chiral alcohols using 10 mM acetophenone, 15 mM 2,5-hexanedione, and 25 mM t-butyl 6-chloro-3,5-dioxohexanoate as substrates (Scheme 2.2.4.5). 

Racemization of (S)-l-phenylethanol in the presence of an Ru p-cymerie binu-clear complex and triethylamine was much faster in [BMIm][BF4] or [BMIm][PF,s] than in toluene [136]. A range of chiral alcohols (Figure 10.17) were resolved in the presence of this complex and immobilized PsL. The reactions were performed in [BM Im][PF6] with the activated ester 2,2,2-trifluoroethyl acetate as the acyl donor (Figure 10.17). A hydrogen donor was required to prevent the formation of partially oxidized byproducts. Enantiomerically pure acetates were isolated in high yield (>85%). 

A somewhat different approach to determining the enantiopurity of a sample is based on the idea that an appropriate enzyme selectively processes one enantiomer, giving rise to a UV/visible signal [17]. An example concerns determination of the enantiopurity of chiral secondary alcohols, the (S) enantiomer being oxidized selectively by the alcohol dehydrogenase from Thermoanaerobium sp. The rate of this process can be monitored by a UV/visible plate reader due to the formation of NADPH (absorption at 340 nm), which relates to the quantity of the (S) enandomer present in the mixture. About 4800 ee determinadons are possible per day, accuracy amoundng to 10%. Although the screen was not specifically developed to evaluate chiral alcohols produced by an enzymadc process, it is conceivable that this could be possible after an appropriate extraction process. 

Conventional gas chromatography (GC) based on the use of chiral stationary phases can handle only a few dozen ee determinations per day. In some instances GC can be modified so that, in optimal situations, about 700 exact ee and E determinations are possible per day [29]. Such meclium-throughputmay suffice in certain applications. The example concerns the lipase-catalyzed kinetic resolution of the chiral alcohol (R)- and (S)-18 with formation of the acylated forms (R)- and (S )-19. Thousands of mutants of the lipase from Pseudomonas aeruginosa were created by error-prone PCR for use as catalysts in the model reaction and were then screened for enantioselectivity [29]. 

Another fluorescence-based method for assaying activity and enantioselectivity of synthetic catalysts, specifically in the acylation of chiral alcohols, was recently reported [27]. The idea is to use a molecular sensor that fluoresces upon formation of an acidic product (acetic acid). Adaptation to high-throughput evaluation of enantioselective lipases or esterases needs to be demonstrated. 

Alkanes are preferentially hydroxylated at the more nucleophilic C—H bonds, with relative reactivities tertiary secondary primary hydrogens = 7000 110 l.303 This reaction occurs with a high retention of configuration at the hydroxylated carbon atom, as shown by the selective formation of cis-9-decalol from the oxidation of cis-decalin with chromyl acetate in an acidic medium304 and the hydroxylation of chiral (+)-3-methylheptane (91) to chiral alcohol (92) with 72 to 85% retention of configuration.305... 

Isomerization of chiral propargyl alcohols.1 The isomerization of chiral alcohols of the type RCHOHC,=C(CH2)nCH3 to terminal acetylenic alcohols, RCHOH(CH2)n + 1C=CH, in the presence of KAPA occurs with no significant loss of enantiomeric purity. Evidently, formation of the alkoxide suppresses racemization. Retention of configuration is observed even when the triple bond moves through several methylene groups. 

Table 8. Preparation of chiral alcohols by enzyme-catalyzed reduction of the corresponding ketones with ADH from Lactobacillus kefir. The production of phenylethanol with formate and formate dehydrogenase (FDH) for coenzyme regeneration was carried out continuously in an enzyme-membrane-reactor...

Table 16. Chiral alcohols produced by continuous enzyme-catalyzed processes. The corresponding ketones are reduced with (S)-ADH from Rhodococcus erythropolis, NADH was regenerated by simultaneous coupling with formate dehydrogenase from Candida boidinii (FDH) and formate (data from [159])...

In most cases, chiral alcohol and phenol derivatives are used as host compounds for the resolution. In these cases, guest molecules are accommodated in the complex by formation of hydrogen bond with the hydroxyl group of the host. Since the hydrogen bond is not very strong, the included guest compound can be recovered easily from the inclusion complex by distillation, recrystallization, chromatography or some other simple procedures. 

Recently, complex formation reactions of (A,A)-tartaric acid (TA) and its 0,0 -dibenzoyl derivative (DBTA) with a series of chiral alcohols (26, 27, 8 and 28, Scheme 11) were investigated in our laboratory using Toda s suspension method. [35] As an example, resolution of 28 is outlined in Scheme 12. 

---