Highly Enantioselective Ketone-Ene Reactions of Trifluoropyruvate: Significant Counterion Effect of the In (III)− PyBox Complex (original) (raw)
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ChemInform Abstract: Enantioselective Carbonylation Reactions
ChemInform, 2009
A highly enantioselective carbonyl-ene reaction of trifluoropyruvate catalyzed by a recyclable indiumA C H T U N G T R E N N U N G (III)-pybox complex in ionic liquid afforded trifluoromethyl-containing tertiary homoallylic alcohols with excellent yields (up to 98%) and enantioselectivities (up to 98% ee). Notably, this catalytic system can be recycled up to seven cycles.
2012
The development of novel synthetic methods for the rapid and stereoselective preparation of complex molecular scaffolds constitutes the driving force behind organic synthesis. [1] In the past decade, organocatalytic [2] methods have emerged as complementary to organometallic-based techniques for catalysed transformations. In particular, enamine, [3] iminium, [4] and SOMO catalysis, [5] as well as photocatalysis [6] have contributed to the enhanced synthetic utility and versatility of carbonyl compounds. The stereoselective alkylation of carbonyl groups (aldehydes and ketones) has been achieved through conceptually different activation modes. [7] Recently, we introduced the concept of enantioselective S N 1-type alkylations to organocatalysis, [8, 9] and also established the compatibility of indiumA C H T U N G T R E N N U N G (III) Lewis acids with organocatalytic processes mediated by the MacMillan catalyst. [10, 11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts in these processes creates the possibility of using carbocations that cannot be generated in the presence of Brønsted acids. [12] The stability of the carbocation involved in the process is the primary driving force for these S N 1-type reactions, and their use can be easily rationalized by the work of Mayr et al. [13] In the presence of InBr 3 , allylic alcohols can provide straightforward access to alkylated aldehydes without the use of palladium or iridium salts. [14] Herein, we report an extension to the scope of our methods to include benzylic and benzhydrylic alcohols, substrates which give access to useful intermediates for the synthesis of biologically active enantioenriched diarylethane products. [15] This structural motif has a diverse range of biological properties that include anticancer, antidepressant, and antiviral activity. [16] We envisioned the direct synthesis of enantioenriched diarylethanes from readily available racemic diarylmethanols (Table 1). We have established a correlation between the electrophilicity (E) of the carbenium ion employed in our S N 1-type reaction and the possibility of generating such an ion. Alcohols that form carbenium ions located at À1 or above on the Mayr scale are not reactive with the enamine that is formed in situ with the MacMillan catalyst. [17] Even in the presence of strong acids, the carbenium ions are not formed or are intercepted by water. Alternatively, by using indiumA C H T U N G T R E N N U N G (III) salts (triflate or bromide), the corresponding carbenium ion can be generated from the alcohols and intercepted by the enamine formed in situ with the MacMillan catalyst. [10-11] The compatibility of indiumA C H T U N G T R E N N U N G (III) salts with water, the amine, and an excess of aldehyde is the motivation for investigating this chemistry. The reactions of model substrates 2 a-c were investigated in the presence of different Lewis acids and under various conditions. The 4-MeO derivative 2 a was rather unreactive and afforded the desired product in 75 % yield as a 1:1 diastereomeric mixture in 76 and 59 % ee after 24 h, with InBr 3 as the Lewis acid in CH 2 Cl 2 (Table 1, entry 1). Many other benzhydrylic derivatives bearing the methoxy substituent were tested, but the reactions gave poor results. In our preceding publications we have established that steric hindrance of the incoming carbenium ion controls the stereoselectivity of the reaction. [11] Therefore, to increase the stereoselectivity and reactivity, derivatives 2 b and 2 c were tested. The reaction conditions were carefully optimized by varying the solvent, Lewis acid, and MacMillan catalyst used in the reaction. Substrate 2 c is more sterically demanding because of the diphenyl substituent. The introduction of an ortho substituent results in more steric hindrance in the carbenium ion, which in turn introduces a steric bias for the enamine that is formed in situ with the MacMillan catalyst. In general, different Brønsted or Lewis acids are able to promote the formation of the corresponding carbenium ion and are compatible with secondary amines and excess aldehydes. However, only InA C H T U N G T R E N N U N G (OTf) 3 ensured high stereoselectivity in this reaction. By varying the solvent excellent stereoselectivity was obtained with catalyst 3 b. Different benzhydrylic substituents were then tested and the data obtained are shown in Table 2. The diastereoselectivity is
Helvetica Chimica Acta, 1981
Dioxolanones 7 and 8a and oxazolinones 9 a derived from pivalaldehyde and lactic acid, mandelic acid, and proline, respectively, furnish chiral enolates of type 3 by deprotonation with LDA. Reactions of these enolates with akyl halides, aldehydes, and ketones ( 4 8b, 9b, 11-13) are highly diastereoselective. Thus, the overall enantioselective u-alkylation of chiral, non-racemic a-heterosubstituted carboxylic acids (4 6 ) is realized. Continuing our search for chiral reagents derived from readily available enantiomerically pure starting materials ('chiral pool') [I], we recently investigated the enolates of type 1 (from b-hydroxy-butyrate [2], malate [2-41, N-formylaspartate IS]) and 2 (from 2,3-O-isopropylidentartrate [6]). We now report preliminary results R 1 2 4 (X=NR,O,S) 5a (cis) 6a HX~FE R1 * = k 2 R2 3a 3b 5b (trans)
Catalysis Today, 2008
In this work it is studied the enantioselective hydrogenation of ethyl pyruvate using a Pt/SiO 2 catalyst, modified with different chiral auxiliaries: (S)-(+)-1-aminoindan, (1R, 2S)-(+)-cis-1-amino-2-indanol and (S)-(+)-1-indanol. Cinchonidine modified system was taken as reference. It is analyzed the influence of the particle size of the catalyst, the molecular structure of the modifier and the nature of the solvent. The enantioselective hydrogenation of ethyl pyruvate resulted to be a structure-sensitive reaction, and accordingly, the Pt/SiO 2 (B) catalyst (dp = 6.5 nm) provided the best results. The modifier (S)-(+)-1-aminoindan presented an ee of 63%, whereas (S)-(+)-1-indanol gave a racemic mixture and (1R, 2S)-(+)-cis-1amino-2-indanol showed an effect of ''erosion of enantiomeric excess''. Concerning the solvent, a higher ee in 2-propanol was obtained when the modifier used was the (S)-(+)-1-aminoindan, while in toluene, n-heptane and acetic acid the performance of the catalytic systems was not good.