Prochiral acyclic

Prochiral acyclic olefins have been used in the reaction with an aryl Grignard reagent. With the complex of nickel(II) chloride and chiraphos (2), a high enantioselectivity could be obtained, albeit with poor rcgiosclecdvity (Eq. 8E.26) [204]. When the sterically more bulky 1,3-diphenylallyl... 

Desymmetrization via proline-catalyzed asymmetric intramolecular aldol reaction can, however, also be performed with acydic diketones of type 109 as has been reported by the Agami group [106], In the first step a prochiral acyclic diketone reacts in the presence of L-proline as catalyst (22-112 mol%) with formation of the aldol adduct 111 (Scheme 6.49). In this step reaction products with two stereogenic centers, 110, are formed. These chiral hydroxyketones 110 are subsequently converted, via dehydration, into the enones 111, by treatment with p-toluenesulfonic acid. 

Asymmetric reduction of cyclic ketones. Prochiral cyclic ketones are reduced to (R)-alcohols in 75-96% ee by a chiral hydride obtained by refluxing a mixture of lithium aluminum hydride, (— )-N-methylephedrine (1 equiv.), and 2-ethylaminopyridine (2 equiv.) in ether for 3 hours. Reduction of prochiral acyclic ketones with this hydride also results in (R)-alcohols, but only in moderate yield. 

A broad spectrum of stereospecific reductions of prochiral acyclic ketones has been recorded (Scheme 4). These arise by enzyme-controlled delivery of the hydride equivalent to only one of the two enantiotopic faces of a C=0 group. Such reductions are achievable with many different oxidoreductases, as illustrated for the conversions of (5a) - (6a) with GDH, of (5b-d) (6b-d) with of... 

Table 11.1-2. Pig liver esterase-catalyzed enantiotopos-differentiating hydrolysis of prochiral acyclic dicarboxylic acid diesters in aqueous solution.

Table 11.1-12. Lipase-catalyzed enantiotopos-differentiating hydrolysis of prochiral acyclic and cyclic dicarboxylic acid diesters in aqueous solution (CCL Candida cylindracea lipase, PPL pig pancreas lipase, PSL Pseudomonas sp. lipase, CVL Chromobacterium viscosum lipase,...

Yamaguchi and coworkers have found that proline rubidium salts catalyze the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When (25)-L-prolines are used, acyclic ( )-enones give (S)-adducts. Cyclic (Z)-enones give (R)-adducts predominantly (Eq. 4.139).203 Recently, Hanessianhas reported that L-proline (3 7% mol equiv) and 2,5-dimethylpiperazine are more effective to induce catalytic asymmetric conjugate addition of nitroalkanes to cycloal-kanones.204... 

For diene ligands which are prochiral, complexation results in the formation of a racemic mixture. Resolution of this racemic mixture has been accomplished via either classical methods102, chromatographic separation on chiral stationary phases103 or kinetic resolution104. For certain acyclic or cyclic dienes possessing a pendent chiral center(s)... 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

Trost and his co-workers succeeded in the allylic alkylation of prochiral carbon-centered nucleophiles in the presence of Trost s ligand 118 and obtained the corresponding allylated compounds with an excellent enantioselec-tivity. A variety of prochiral carbon-centered nucleophiles such as / -keto esters, a-substituted ketones, and 3-aryl oxindoles are available for this asymmetric reaction (Scheme jg) Il3,ll3a-ll3g Q jjg recently, highly enantioselective allylation of acyclic ketones such as acetophenone derivatives has been reported by Hou and his co-workers, Trost and and Stoltz and Behenna - (Scheme 18-1). On the other hand, Ito and Kuwano... 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

A number of examples of monoacylated diols produced by enzymatic hydrolysis of prochiral carboxylates are presented in Table 3. PLE-catalyzed conversions of acyclic diesters strongly depend on the structure of the substituent and are usually poor for alkyl derivatives. Lipases are much less sensitive to the structure of the side chain the yields and selectivity of the hydrolysis of both alkyl (26) and aryl (24) derivatives are similar. The enzyme selectivity depends not only on the structure of the alcohol, but also on the nature of the acyl moiety (48). 

When a prochiral nucleophile is reacted with 1,3-disubstituted allylic systems, the issue of diastereo- as well as enantioselectivity arises. In the alkylation of a tetralone, both the acyclic... 

Whereas preparation of a-amino acid derivatives by asymmetric allylation of an acyclic iminoglycinate gave a modest enantioselectivity (62% ee) in an early investigation [189], the use of conformationally constrained nucleophiles in an analogous alkylation resulted in high selectivities (Scheme 8E.43) [190], With 2-cyclohexenyl acetate, the alkylation of azlactones occurred with good diastereomeric ratios as well as excellent enantioselectivities. This method provides very facile access to a variety of a-alkylamino acids, which are difficult to synthesize by other methods. When a series of azlactones were alkylated with a prochiral gem-diacetate, excellent enantioselectivities were uniformly obtained for both the major and minor diastereom-ers (Eq. 8E.20 and Table 8E.12). 

A rubidium salt of proline (5-10 mol%) has been reported to catalyse the asymmetric Michael addition of nitroalkanes to prochiral acceptors. When L-proline was used, acyclic (I )-enones produced (.S )-adducts. whereas cyclic (Z)-enones gave (R )-adducts.88... 

Metal-based asymmetric phase-transfer catalysts have mainly been used to catalyze two carbon-carbon bond-forming reactions (1) the asymmetric alkylation of amino acid-derived enolates and (2) Darzens condensations [5]. The alkylation ofprochiral glycine or alanine derivatives [3] is a popular and successful strategy for the preparation of acyclic a-amino acids and a-methyl-a-amino acids respectively (Scheme 8.1). In order to facilitate the generation of these enolates and to protect the amine substituent, an imine moiety is used to increase the acidity of the a-hydrogens, and therefore allow the use of relatively mild bases (such as metal hydroxides) to achieve the alkylation. In the case of a prochiral glycine-derived imine (Scheme 8.1 R3 = H), if monoalkylation is desired, the new chiral methine group... 

The results of the hydroformylation of internal olefins are reported in Table 9. In the case of (Z)- and (E)-2-butene, the same fare of the unsaturated carbon atom is formylated with either a rhodium- or platinum (—)-DIOP-containing catalytic system. With the rhodium catalyst, when an acyclic olefin is used as the substrate, the same fare is always attacked, and it is only the notation but not the geometric requirement that is different for (E)-l-phenyl-1-propene. The only exception is represented by bicyclo[2,2,l]heptene. However, using (—)-CHIRAPHOS instead of (—)-DIOP, also bieyelo[2,2,l]heptene behaves like internal butenes. No regularity is observed for the cobalt or ruthenium (—)-DIOP catalytic systems. With the same system, only in 3 cases out of 15 the face of the prochiral atom preferentially formylated has different geometric requirements. 

Desymmetrization of prochiral cyclic anhydrides In the presence of the chiral nucleophilic catalyst (e.g. A, Scheme 13.1, top) one of the enantiotopic carbonyl groups of the prochiral (usually meso) cyclic anhydride substrate is selectively converted into an ester. Application of catalyst B (usually the enantiomer or a pseudoenantiomer of A) results in generation of the enantiomeric product ester. Ideally, 100% of one enantiomerically pure product can be generated from the starting anhydride. No reports of desymmetrizing alcoholyses of acyclic meso anhydrides appear to exist in the literature. 

Since the discoveries of Itsuno32 and Corey,33 remarkable advances have been made in the enantio-selective reduction of prochiral ketones using amino alcohol-derived oxazaborolidines (see Chapter 16).34 35 In most cases, these amino alcohols were obtained from chiral pool sources. Consequently, extensive synthetic manipulations were often necessary to access their unnatural antipode. Didier and co-workers were first to examine the potential of m-aminoindanol as a ligand for the asymmetric oxazaborolidine reduction of ketones.36 Several acyclic and cyclic amino alcohols were screened for the reduction of acetophenone (Scheme 17.2), and m-aminoindanol led to the highest enantioselectivity (87% ee). 

In order to utilize such a chiral substructure as a source of absolute stereoehemical information in a synthesis, it is necessary to employ the complexes A and ent-A in non-racemie form. While the enan-tioselective preparation of such chiral complexes was achieved in the past more or less exclusively via resolution of raeemic mixtures, the diastereo-selective complexation of chirally modified ligands was shown more recently to be a practical alternative [2]. Another possibility, the enantiose-lective conversion of prochiral metal complexes by means of chiral reagents, has been achieved by W. R. Roush 3]. In a remarkable (formal) total synthesis of the antibiotic (-i-)-ikarugamycin (1), Roush et al. apply their method and demonstrate in a highly convincing fashion the synthetic usefulness of acyclic butadiene-FefCOfj complexes [4]. 

Asymmetric reduction of oi, -enones. Prochiral cyclic and acyclic a,p-enones are reduced by lithium aluminum hydride complexed with 1 to (S)-allylic alcohols in optical yields of 30-100% (equation 1). 

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