Asymmetric Diels-Alder-related Reactions

3 Asymmetric Inverse-electron-demand Diels-Alder Reaction 

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E = As, Sb or Bi) react similarly with Grignard reagents, providing routes to cyclic arsines, stibines and bismuthines. Leung s group has reported further applications of asymmetric Diels-Alder cyclisation reactions in phosphine synthesis. A platinum complex chiral auxiliary has been used to promote the asymmetric [4-1-2] Diels-Alder addition of diphenyl(vinyl)-phosphine to 3-diphenylphosphinofuran, giving the eradocycloadduct (70) as the predominant stereoisomer. Related cycloadditions between 3,4-dimethyl-1 -phenylphosphole and ester-functionalised allylic phosphines have provided chemoselective routes to optically-pure P-chiral 1,2- and... 

Catalytic asymmetric Diels-Alder reactions are presented by Hayashi, who takes as the starting point the synthetically useful breakthrough in 1979 by Koga et al. The various chiral Lewis acids which can catalyze the reaction of different dieno-philes are presented. Closely related to the Diels-Alder reaction is the [3-1-2] carbo-cyclic cycloaddition of palladium trimethylenemethane with alkenes, discovered by Trost and Chan. In the second chapter Chan provides some brief background information about this class of cycloaddition reaction, but concentrates primarily on recent advances. The part of the book dealing with carbo-cycloaddition reactions is... 

Ghosh et al. [70] reviewed a few years ago the utihty of C2-symmetric chiral bis(oxazoline)-metal complexes for catalytic asymmetric synthesis, and they reserved an important place for Diels-Alder and related transformations. Bis(oxazoline) copper(II)triflate derivatives have been indeed described by Evans et al. as effective catalysts for the asymmetric Diels-Alder reaction [71]. The bis(oxazoline) Ugand 54 allowed the Diels-Alder transformation of two-point binding N-acylimide dienophiles with good yields, good diastereos-electivities (in favor of the endo diastereoisomer) and excellent ee values (up to 99%) [72]. These substrates represent the standard test for new catalysts development. To widen the use of Lewis acidic chiral Cu(ll) complexes, Evans et al. prepared and tested bis(oxazoHnyl)pyridine (PyBOx, structure 55, Scheme 26) as ligand [73]. 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted much interest for their various applications in different synthetic transformations.2 Such simple structures, directly related to far better known chiral oxazolidinones,11,12,57 have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations, but mainly in condensation of their /V-acyl derivatives with aldehydes. Chiral OZTs have shown interesting characteristics in anti-selective aldol reactions58 or combined asymmetric addition. 

The preparation of immobilized catalysts related to the imidazolidinone-type organocatalyst 13 and their application in the asymmetric Diels-Alder reaction was reported by Pihko and co-workers [9]. The reactivity of the immobilized catalysts depended on the type of solid support. The silica-supported imidazolidinone 24, which was prepared starting from N-Fmoc-protected L-phenylalanine, was found to be a highly active organocatalyst. Several dienes and a,/i-un saturated aldehydes have been successfully used in the presence of only 3.3 to 20 mol% 24, usually... 

In addition, immobilized catalysts related to the MacMillan imidazolidinone-type organocatalyst 5 have been used for the asymmetric Diels-Alder reaction (Section... 

In the reaction between cyclohexadiene and acrylate, ees as high as 93% could be observed. An ionic liquid composed of a structurally related chiral cation is thus likely to promote asymmetric Diels-Alder reactions. 

Ooi T., Maruoka, K. Hetero-Diels-Alder and related reactions in Compr. Asymmetric Catal. I-III 1999 3 1237 Eds. Jacobsen EN, Pfaltz A and Yamamoto H, Pb. Springer-Verlarg, Berlin... 

Mikami K. Asymmetric Catalysis of Carbonyl-Ene Reactions and Related Carbon-Carbon Bond Forming Reactions Pure Appl. Chem. 1996 68 639 644 Keywords hefero-Diels-Alder reactions, asymmetric catalysis... 

The orbital mixing theory was developed by Inagaki and Fukui [1] to predict the direction of nonequivalent orbital extension of plane-asymmetric olefins and to understand the n facial selectivity. The orbital mixing rules were successfully apphed to understand diverse chemical phenomena [2] and to design n facial selective Diels-Alder reactions [28-34], The applications to the n facial selectivities of Diels-Alder reactions are reviewed by Ishida and Inagaki elesewhere in this volume. Ohwada [26, 27, 35, 36] proposed that the orbital phase relation between the reaction sites and the groups in their environment could control the n facial selectivities and review the orbital phase environments and the selectivities elsewhere in this volume. Here, we review applications of the orbital mixing rules to the n facial selectivities of reactions other than the Diels-Alder reactions. 

In a related reaction, the Danishefsky diene 1434 cyclizes with ethyl pyruvate 1435 in the presence of catalytic amounts of the asymmetric Lewis acid catalyst 1436, at -72 °C in THF, to give the Diels-Alder adduct 1437, in 85% yield and 91% ee, and the ring-opened product 1438, which cyclizes, however, with triflic acid to give 1437 [11] (Scheme 9.9). 

An interesting expansion to the scope of dienes that could be adopted as partners within the Diels-Alder cycloaddition was reported by Deng (Scheme 57) [193]. Reaction of 3-hydroxypyrones 145 with a broad range of a,p-unsaturated ketones in the presence of the primary cinchona alkaloid 144 (5 mol%) provided the Diels-Alder adducts with exceptional levels of asymmetric induction (up to 99% ee). Within this report it was also shown that the related alkaloid 146 provided access to the enantiomeric adducts with similar levels of asymmetric induction. 

Surprisingly, the catalytic potential of proline (1) in asymmetric aldol reactions was not explored further until recently. List et al. reported pioneering studies in 2000 on intermolecular aldol reactions [14, 15]. For example, acetone can be added to a variety of aldehydes, affording the corresponding aldols in excellent yields and enantiomeric purity. The example of iso-butyraldehyde as acceptor is shown in Scheme 1.4. In this example, the product aldol 13 was obtained in 97% isolated yield and with 96% ee [14, 15]. The remarkable chemo- and enantioselectivity observed by List et al. triggered massive further research activity in proline-catalyzed aldol, Mannich, Michael, and related reactions. In the same year, MacMillan et al. reported that the phenylalanine-derived secondary amine 5 catalyzes the Diels-Alder reaction of a,/>-un saturated aldehydes with enantioselectivity up to 94% (Scheme 1.4) [16]. This initial report by MacMillan et al. was followed by numerous further applications of the catalyst 5 and related secondary amines. 

These results indicate that the sulfinyl group seems to be much more efficient in the control of the stereoselectivity of 1,3-dipolar cycloadditions (endo or exo adducts are exclusively obtained in de> 80%) than in Diels-Alder processes (mixtures of all four possible adducts were formed). Additionally, complete control of the regioselectivity of the reaction was observed. Despite these clearly excellent results, the following paper concerning asymmetric cycloaddition of cyclic nitrones and optically pure vinyl sulfoxides was reported nine years later [154]. (Meanwhile, only one paper [155], related to the synthesis of /1-nicotyri-nes, described the use of reaction of nitrones with racemic vinyl sulfoxides, but these substrates were merely used as a masked equivalent of acetylene dipolaro-phile). In 1991, Koizumi et al. described the reaction of one of the best dipolarophiles, the sulfinyl maleimide 109, with 3,4,5,6-tetrahydropyridine 1-oxide 194 [154]. It proceeded in CH2C12 at -78 °C to afford a 60 20 10 6 mixture of four products in ca. 90 % yield (Scheme 92). 

Ooi, T. Maruoka, K. Hetero-Diels-Alder and Related Reactions. In Comprehensive Asymmetric Catalysis Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. Springer Heidelberg, 1999 Vol. 3, pp 1237-1254. 

Surprisingly, little follow-up work on this idea of small molecule asymmetric catalysis appeared for the next 25 years. In the late 1980s, Agami reported the asymmetric intramolecular aldol reaction of acyclic diketones with (S)-proline as the catalyst. It was not nntil the twenty-first centnry, however, when this notion of organocatalysts became fnlly exploited. List and Barbas ° pioneered enam-ines as catalysts for aldol and Mannich and related reactions. MacMillan has developed a variety of imininm-based catalysts prodncing large asymmetric indnction for Diels-Alder chemistry, Friedel-Crafts alkylations, Mnkaiyama-Michael and cyclopropanation " reactions. 

The domino Knoevenagel condensation hetero-Diels-Alder reaction was used for the enantioselective total synthesis of the active anti-influenza A virus indole alkaloid hirsutine and related compounds by L.F. Tietze and co-workers. The Knoevenagel condensation was carried out between an enantiopure aldehyde and Meldrum s acid in the presence of ethyienediamine diacetate. The resulting highly reactive 1-oxa-1,3-butadiene underwent a hetero-Diels-Alder reaction with 4-methoxybenzyi butenyl ether ElZ = 1 1) in situ. The product exhibited a 1,3-asymmetric induction greater than 20 1. 

The great importance of the Diels-Alder and hetero-Diels-Alder reactions in synthesis is a strong stimulus for finding new aspects about them, especially those methodologically related, and chiral catalysts rank high in such a context. Accordingly, 145, ID, and 146 are valuable additions to the list of the metal-free entities, even ID is somewhat inferior due to relatively low asymmetric induction (up to 70% ee) it tenders during the reaction of anthro-nes and maleimides. 

Asymmetric hetero-Diels—Alder and related reactions 99MI24. 

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