Chiral induction observation

Another more efficient catalytic version of the reaction consists of the interaction of ketones with chiral amines [6] to form enolate-like intermediates that are able to react with electrophilic imines. It has been postulated that this reaction takes place via the catalytic cycle depicted in Scheme 33. The chiral amine (130) attacks the sp-hybridized carbon atom of ketene (2) to yield intermediate (131). The Mannich-like reaction between (131) and the imine (2) yields the intermediate (132), whose intramolecular addition-elimination reaction yields the (5-lactam (1) and regenerates the catalyst (130). In spite of the practical interest in this reaction, little work on its mechanism has been reported [104, 105]. Thus, Lectka et al. have performed several MM and B3LYP/6-31G calculations on structures such as (131a-c) in order to ascertain the nature of the intermediates and the origins of the stereocontrol (Scheme 33). According to their results, conformations like those depicted in Scheme 33 for intermediates (131) account for the chiral induction observed in the final cycloadducts. 

It was found that lowering the reaction temperature from rt to — 10°C resulted in an increased enantiomeric excess (from 27% ee to 54% ee). Surprisingly, the addition of small amounts of water (ca. 20 mol %) also increased the chiral induction observed (up to 89% ee). 

More recently, a study by Lassaletta, Fernandez and co-workers showed that enantioselective NHC-Ag catalysis was not an impossible goal. Hence, the use of polydentate thiolato-NHCs 11-14 afforded good enantioselectivities in the 1,3-dipolar cycloaddition of azomethine ylides with acrylates (Scheme 11.4). ° Ligand 11 systematically produced the highest ee s (up to 80% ee) with a number of imino esters. The authors proposed that a tridentate SCS coordination of these C2-symmetric ligands onto the silver center was key for obtaining the good chiral induction observed in the cycloaddition. 

The assumed transition state for this reaction is shown in Scheme 5.5. The two bulky t-butoxy groups are expected to locate at the two apical positions. One of the 3,3 -phenyl groups would effectively shield one face of an imine, and consequently, a diene attacks from the opposite side. Judging from this model, similar selectivities were expected in the Mannich-type reactions of imines with silyl eno-lates. Actually, when ligand 10 was used in the reaction of imine la with S-ethyl-thio-l-trimethylsiloxyethene, the corresponding / -amino thioester was obtained in 84% ee (Scheme 5.6). As expected, the sense of the chiral induction in this case was the reverse of that observed when using catalyst 6 [12, 25]. 

The complexation procedure included addition of an equimolar amount of R,R-DBFOX/Ph to a suspension of a metal salt in dichloromethane. A clear solution resulted after stirring for a few hours at room temperature, indicating that formation of the complex was complete. The resulting solution containing the catalyst complex was used to promote asymmetric Diels-Alder reactions between cyclopen-tadiene and 3-acryloyl-2-oxazolidinone. Both the catalytic activity of the catalysts and levels of chirality induction were evaluated on the basis of the enantio-selectivities observed for the endo cycloadduct. 

Recent studies on isolated BVMOs using Rh-complexes as NADPH substitutes for facile cofactor recycling suggested a pivotal role of the native cofactor to generate the proper environment within chiral induction in sulfoxidation reactions. While biooxidation was still observed in the presence of the metal complex, stereoselectivity of the enzyme was lost almost completely [202]. 

Allyltitanium complexes derived from a chiral acetal have been reacted with carbonyl compounds and imines [63], While the chiral induction proved to be low with carbonyl compounds, high induction was observed with imines. This complex represents the first chiral homoenolate equivalent that reacts efficiently with imines. Finally, the reactions with electrophiles other than carbonyl compounds and imines, namely a proton source, NCS, and I2, furnished the corresponding alkene, chloro, and iodo derivatives in good yields [64]. 

On thermolysis, appropriately substituted A-allyl-A-silyloxy enamines 19 undergo smooth [3,3]-sigmatropic rearrangements to the corresponding A-silyloxy imino ethers laP (equation 5). Two stereogenic centers are created but no reference to chiral induction is referred. High diastereoselectivity was observed and short reaction times favoured the syn A-silyloxy imino ether diastereomers. 

Achiral ester-substituted nitrones as well as chiral nitrones can be employed in diastereoselective asymmetric versions of tandem transesterification/[3 + 21-cycloaddition reactions, as shown in Scheme 11.54 (174). High diastereoselectivity and excellent chemical yields have been observed in the reaction with a (Z)-allylic alcohol having a chiral center at the a-position in the presence of a catalytic amount of TiCl4- On the other hand, the reaction with an ( )-allylic alcohol having a chiral center at the a-position, under similar conditions, affords very low selectivities. Tamura et al. has solved this problem with a double chiral induction method. Thus, high diastereoselectivity has been attained by use of a chiral nitrone. 

An interesting reversal of chiral induction in chromium(III)-salen complexes using a tartaric derived alicyclic diamine moiety (i.e., 7) has been observed by Mosset, Saalfrank, and co-workers <99T1063>. Thus, epoxidation of the chromene 8 using catalyst 7 and an oxidant consisting of MCPBA/NMO afforded the 3S,4S epoxide 9, whereas the Jacobsen catalyst (1) provided the corresponding 3R,4R enantiomer. A mechanistic rationalization for this curious crossover has not yet been proposed. 

Special cases arc the enantioselective synthesis of chiral aldehydes using 1-phenyl-l-ethanamine under optimized conditions (see Table 5), and the remarkable asymmetric induction observed in the alkylation of polymer-bound imines at room temperature (see Table 2). 

The use of chiral sulfoxides to transfer the chirality from sulfur to the a carbon has been investigated, and the high asymmetric induction observed in chiral acyclic sulfoxides using a silicon-induced Pummerer-typc reaction is noteworthy [249]. 

The appreciable levels of asymmetric induction observed in the catalytic ARCM reactions mentioned above suggest a high degree of enantiodifferentiation in the association of olefinic substrates and chiral complexes. This stereochemical induction may also be exploited in asymmetric ring-opening metathesis (AROM). Catalytic ROM transformations [20] offer unique and powerful methods for the preparation of complex molecules [2d, 2g]. The chiral Mo-alkyli-denes that are products of AROM reactions can be trapped either intramolecu-larly (RCM) or intermolecularly (cross metathesis, CM) to afford a range of optically enriched adducts. 

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