Asymmetric alcoholysis

Asymmetric alcoholyses catalyzed by lipases have been employed for the resolution of lactones with high enantioselectivity. The racemic P-lactone (oxetan-2-one) illustrated in Figure 6.21 was resolved by a lipase-catalyzed alcoholysis to give the corresponding (2S,3 S)-hydroxy benzyl ester and the remaining (3R,4R)-lactone [68]. Tropic acid lactone was resolved by a similar procedure [69]. These reactions are promoted by releasing the strain in the four-membered ring. 

Other silicon derivatives containing Si—X—C bonds (where X is O and/or N) can be successfully prepared by using iridium-catalyzed reachons such as the asymmetric hydrosilylation of ketones and amines, the silylcarbonylation of alkenes, and the alcoholysis of Si—H bonds. Indeed, oxygenation of the latter bond to silanol also proceeds smoothly in the presence of iridium compounds. 

Deng also showed that (DHQD)2AQN could catalyze the parallel KR (PKR) of a variety of monosubstituted succinic anhydrides via asymmetric alcoholysis [215]. The nature of the solvent was found to have a significant influence on the selectivity. Hence, increasing the size of the alcohol from methanol to ethanol resulted in increased levels of enantioselectivity, albeit with reduced reaction rates. In this context, 2,2,2-trifluoroethanol appeared to be the alcohol of choice as it allowed the ASD of 2-methyl succinic anhydride (58a) with a remarkable level of selectivity. Indeed, the use of (DHQD)2AQN (15 mol%) provided a mixture of two regioiso-meric hemiesters 59a and 60a in a 1 1 ratio with 93 and 80% ee respectively. 

A study on the combined use of a chiral substrate obtained by alcoholysis of a 4-benzylidene-5(4//)-oxazolone with a chiral alcohol coupled with hydrogenation using a chiral catalyst has also been described. This work shows that the matching effect of double asymmetric induction in hydrogenation can be modulated by a solvent effect. 

To our knowledge, the first examples of asymmetrically substituted monocyclic phosphoranes are 60 and 61, described by Moriarty et al.135 and involving the reaction of a substituted o-benzoquinone136,137 (Scheme 6) on an aminophosphine (59), itself obtained by alcoholysis of 58 with l-( — )-menthol. In contrast to the amino phosphine 53 (Scheme 5), 59 is a mixture of the diastereoisomers 59a and b, and its reaction with 3,5-di-tert-butyl-l,2-benzoquinone yields two diastereoisomeric phosphoranes, 60a and b. Finally, alcoholysis of the P(V)—NR2 bond138 in 60a and b leads to 61a and b or 62. 

Kinetic resolution of chiral, racemic anhydrides In this process the racemic mixture of a chiral anhydride is exposed to the alcohol nucleophile in the presence of a chiral catalyst such as A (Scheme 13.2, middle). Under these conditions, one substrate enantiomer is converted to a mono-ester whereas the other remains unchanged. Application of catalyst B (usually the enantiomer or a pseudo-enantiomer of A) results in transformation/non-transformation of the enantiomeric starting anhydride ). As usual for kinetic resolution, substrate conversion/product yield(s) are intrinsically limited to a maximum of 50%. For normal anhydrides (X = CR2), both carbonyl groups can engage in ester formation, and the product formulas in Scheme 13.1 are drawn arbitrarily. This section also covers the catalytic asymmetric alcoholysis of a-hydroxy acid O-carboxy anhydrides (X = O) and of a-amino acid N-carboxy anhydrides (X = NR). In these reactions the electrophilicity of the carbonyl groups flanking X is reduced and regioselective attack of the alcohol nucleophile on the other carbonyl function results. 

Sato and coworkers have reported an asymmetric synthesis of Baylis-Hillman-type allylic alcohols 48, 49 via a chiral acetylenic ester titanium alkoxide complex (Scheme 9) [41]. These reactions rely on the use of the novel acetylenic ester titanium alkoxide complex 44 with a camphor-derived chiral auxiliary. Optically active, stereodefined hydroxy acrylates 46, 47 were obtained in high yields and with excellent regio- and diastereoselectivities. The chiral auxiliary was subsequently cleaved off by alcoholysis. 

It might be anticipated that, if a racemic unsymmetrically substituted cyclic anhydride were to be used as a substrate for asymmetric alcoholysis, a KR would ensue. In fact, Deng has shown that for monosubstituted succinic anhydrides, because both carbonyl groups have comparable reactivity, what actually occurs on subjection to his (DHQD)2AQN-catalyzed asymmetric alcoholysis conditions, is a PKR [188]. Thus, the reaction of 2-methyl succinic anhydride (39a) with 2,2,2-trifluoroethanol (10 equiv.) in ether at —24 °C in the presence of (DHQD)2AQN (15 mol%) provided a mixture of two regioisomeric hemiesters... 

This process proceeds as a DKR [13, 190] because the DMAP catalyst promotes not only the asymmetric alcoholysis of the azlactone but also its racemization under the reaction conditions the N-benzoyl a-amino acid ester product does not racemize under these conditions. Johannsen has also screened chiral DMAP 21 (Fig. 8.4) for this transformation, but obtained poorer yields and selectivities [102],... 

The side-on (r)2) bonding in M r 2-H2 and other a-complexes has been termed non-classical, on analogy to the 3-center, 2-electron bonding in non-classical carbocations and boranes (Fig. 2). One of the first questions raised when H2 complexes were discovered is whether they would be important in catalytic reactions. As will be shown below the answer is an emphatic yes, as exemplified by the elegant asymmetric catalytic hydrogenation systems of Nobel-laureate Ryoji Noyori. Also, the mechanism of catalytic silane alcoholysis directly involves two different a complexes M(r 2-Si-H) and M(r 2-H2). In both of these systems, the crucial step is heterolytic cleavage of the H H and/or Si-H bond, the primary subject of this review. 

Catalytic alcoholysis of silanes by a variety of transition metal based catalysts is a useful method to form silyl ethers under mild conditions (Scheme 19). The process is atom-economical hydrogen gas is the only byproduct. This mild method has not been fully exploited for the preparation of unsymmetrical bis-alkoxysilanes. A catalytic synthesis using silicon alcoholysis would circumvent the need of bases (and the attendant formation of protic byproducts), and eliminate the need for excess silicon dichlorides in the first silyl ether formation. We sought catalytic methods that would ultimately allow formation of chiral tethers that are asymmetric at the silicon center (Scheme 20). Our method, once developed, should be easily transferable for use with high-value synthetic intermediates in a complex target-oriented synthesis therefore, it will be necessary to evaluate the scope and limitation of our new method. 

Under almost anhydrous conditions in organic medium, lipases can be used in the reverse mode for direct ester synthesis from carboxylic acids and alcohols, as well as transesterifications (acyl transfer reactions) which can be divided into alcoholysis (ester and alcohol), acidolysis (ester and acid), and interesterification (ester-ester interchange). The direct esterification and alcoholysis in particular have been most frequently used in asymmetric transformations involving lipases. The parameters that influence enzymatic catalysis in organic solvents have been intensively studied and discussed. ... 

Chen Y, McDaid P, Deng L. Asymmetric alcoholysis of cyclic anhydrides. Chem. Rev. 2003 103 2965-2983. 

Asymmetric Alcoholysis of Dihydrosilanes. Optically active difunctional silanes have been obtained by asymmetric alcoholysis of prochiral dihydrosilanes catalyzed by rhodium complexes (73) (eq. [28]). 

A proposed mechanism for the rhodium-catalyzed alcoholysis is represented in Scheme 49 (77). In the first step, activation of the hydrosilane occurs through oxidative addition. Formation of the alkoxysilane then takes place by nucleophilic attack of a noncoordinated alcohol molecule. The dihydro-rhodium complex 143 thus obtained liberates a hydrogen molecule upon reductive elimination. Nucleophilic cleavage of the silicon-rhodium bond, without prior coordination of the alcohol at the rhodium is supported by results obtained in asymmetric alcoholysis (cf. Sect. II-D). Optical yields were shown to be little dependent on the catalyst ligands (in marked contrast with the asymmetric hydro-silylation), indicating but weak interaction between alcohol and catalyst during the reaction. Moreover, inversion of configuration at silicon, which occurs in the particular case of methanol as solvent, is not likely to occur in a reaction between coordinated silane and alcohol. 

Electrophilic reactions. Asymmetric bromination of alkanoyl chlorides with 1,1,3,6-tetrabromo-l,2-dihydronaphthalen-2-one is catalyzed by the quinine - derived 3, it affords (5)-a-bromoaIkanoic esters on alcoholysis of the products Quatemization of quinine with... 

Ring cleavage. Catalyzed hy Sc(OTf)3, alcoholysis of epoxides and aziridines proceeds at room temperature. The ring opening of mei oepoxides is rendered asymmetric if a chiral ligand such as 1 is added to the reaction medium. Lactones give polymers via alcoholysis. ... 

The first example of an asymmetric induction at tetragonal silicon was reported by Klebe and Finkbeiner42 and is shown in equation 3. The reaction of a prochiral bis-(acetamido)silane with optically active amino acids led to two diastereomeric 2-silaoxa-zolidones in unequal amounts. These diastereomers were shown to undergo a second-order asymmetric transformation crystallization was accompanied by a rearrangement of the less abundant into the more abundant diastereomer. From the silaoxazolidones, alcoholysis reactions yielded an optically active dialkoxysilane. 

Asymmetric alcoholysis. The asymmetric alcoholysis of dihydrosilanes was studied in the presence of a rhodium catalyst45 (equation 5). 

TABLE 2. Asymmetric alcoholysis of dihydrosilanes in the presence of (Ph3P)3RhCl (after Reference 45)... 

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