Treatment of the chiral oxazaborolidine 1 with AlBr3 generates the 1:1 complex 3, which is an even more potent Lewis acid catalyst than protonated 1 (i.e., 2) for enantioselective Diels−Alder reactions. Only 4 mol % of catalyst 3 is required to achieve yields and enantiomeric purities of 90% over a broad range of achiral dienes and dienophiles. The ligand from which 3 is derived can be recovered easily and with high efficiency. The method is illustrated by 22 examples.
A highly electron-donating and conformationally rigid P-chiral bis(trialkylphospholane) ligand 2 (DuanPhos) has been prepared in both enantiomeric forms through a concise synthesis. Rh-2 complex has exhibited remarkably high enantioselectivities (up to Ͼ99% ee) and reactivities (up to 10,000 TON) for the hydrogenation of a wide variety of functionTransition metal-catalyzed asymmetric hydrogenation of prochiral double bonds using such elements as Rh, Ru and Ir represents one of the most practical and efficient methods for the preparation of chiral building blocks.[1] Tremendous effort has been devoted into this field during the last few decades, especially the development of chiral phosphorus ligands that can provide not only high enantioselectivities, but also high reactivities.[2] However, the substrate scope of hydrogenation for a particular ligand or ligand family is generally very limited with only few exceptions such as BINAP [3] and DuPhos. [4] While there is no universal ligand, the search for more practical ligands with ready availability, high enantioselectivity and reactivity, and broad substrate scope remains an important goal in asymmetric hydrogenation.P-chiral phosphorus ligands are highly likely to be a superior class of ligands for asymmetric catalysis because of their abilities to bring the chiral environment to the closest proximity to the transition metal centers. Dramatic results by Knowles using P-chiral DIPAMP ligand for Rh-catalyzed hydrogenation in 1970s opened the field of asymmetric catalysis.[5] However, it took nearly two decades for other groups to discover efficient methods to prepare Pchiral phosphane compounds largely due to the synthetic difficulties in construction of stereogenic phosphorus centers. [6,7] Moreover, a major drawback of many P-chiral phosphane synthetic methods developed by Imamoto, [6a] Juge, [6b] Corey, [6c] Evans, [6e] and Livinghouse [6g] is that either only one enantiomer of ligand is readily accessible due to the nature of the chiral auxiliaries they used in the ste- Figure 1. Structures of a new class of highly electron-donating and conformationally rigid bis(trialkylphospholane) ligands reogenic center formation step or a tedious diastereomeric derivatization, separation and deprotection sequence was involved. Thus, an overwhelming challenge in this field is to prepare both enantiomers of P-chiral ligands in a practical way. We have designed many conformationally rigid chiral bis-(phosphanes) for achieving high enantioselectivities in asymmetric hydrogenation.[8] To reach high turnover number (TON) and turnover frequency (TOF) as well, we envisioned that bis(trialkylphosphanes), especially with tertbutyl groups, would be a particular class of electron-donating ligands and their Rh complexes would be highly active and represent a new generation of hydrogenation catalysts. For instance, a bis(trialkylphosphane) ligand developed by Hoge [9] provided 10 times more turnovers for the hydrogenation of an alkene than the bis(dialkylarylphosphane) DuPhos. Re...
A variety of triazole-based monophosphines (ClickPhos) have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes. Their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides. Ligand 7i, which has a 2,6-dimethoxybenzene moiety, provided good results in Suzuki-Miyaura reaction to form hindered biaryls. A CAChe model for the Pd/7i complex shows that the likelihood of a Pd-arene interaction might be a rationale for its high catalytic reactivity.
Efficient methodology has been developed for the conjugate addition of ketene acetals to cyclic alpha,beta-enones. The chiral adducts allow access to fused- or bridged-ring structures such as those shown.
Enantioselective hydrogenation of amino ketones catalyzed by Ru- [1] or Rh-phosphine [2] complexes provides an efficient method for the synthesis of enantiomerically active amino alcohols, a class of chiral compounds of great importance in pharmaceutical products. A recent challenging target [3] inspired us to look for a practical solution for the enantioselective reduction of b-amino ketones with a secondary amino group, an unsolved class of substrates in asymmetric hydrogenation. To our knowledge, no Ru catalytic system has successfully been used for the asymmetric hydrogenation of amino ketones with a secondary amino group. A Rh-MCCPM (MCCPM = (2S,4S)-4-dicyclohexylphosphino-2-diphenylphosphinomethyl-1-(N-methylcarbamoyl)pyrrolidine) catalyst has been reported for the hydrogenation of one b-secondary-amino ketone substrate with only moderate efficiency (80 % ee, turnover number (TON) = 1000).[2e]Given the importance of chiral g-amino alcohols 2 as key intermediates for the synthesis of pharmaceutical products 1 [4] (Scheme 1), an efficient enantioselective reduction of bsecondary-amino ketones 3 into 2 would be of great significance, not only for pharmaceutical development but also as a generally useful organic transformation. Herein, we report a Rh-catalyzed highly efficient hydrogenation of a series of b-secondary-amino ketones with ee values of up to > 99 % and with turnover numbers of more than 4500; this hydrogenation provides a potentially practical synthesis of key pharmaceutical intermediates.g-Secondary amino alcohols 2 are of particular interest to synthetic chemists as they are key intermediates for the synthesis of an important class of antidepressants, 1 a-d. [4] Owing to the different biological activities exhibited by individual enantiomers of 1, a number of enantioselective syntheses of 1, as well as of 2, have been developed in recent years.[5] Although highly enantioselective hydrogenation of btertiary-amino ketones, catalyzed by a chiral [RuCl 2 (diphosphine)(1,2-diamine)] complex, provides an effective route for the enantioselective syntheses of 1, [1c-e] subsequent selective removal of one N-methyl group is needed to afford the desired amino alcohols 2.[5b] A direct hydrogenation of bsecondary-amino ketones 3 would be a more attractive and economic strategy for the syntheses of 2. However, Ru systems have not been effective for the latter reduction so far. Recently, we revealed the synthesis of a highly electrondonating P-chiral trialkylbisphospholane ligand, 4 (duanphos, see Scheme 2), in both enantiomeric forms.[6] The high reactivities and enantioselectivities observed in the Rhduanphos-catalyzed hydrogenation of various types of functionalized C = C bonds [6] suggest the feasibility of using the Rh-duanphos system for the reduction of the C = O bond in amino ketones, provided a proper metal-substrate chelate forms through coordination of the nitrogen atom to the metallic center.
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