Asymmetric reactions Alder-Ene reaction

Enantio- and diastereoselective syntheses of a variety of heterocycles were accomplished by combining the ruthenium-catalyzed Alder-ene reaction with a palladium-catalyzed asymmetric allylic alkylation (AAA) (Scheme 7). For the AAA, y>-nitrophenol was found to function as a suitable leaving group and yet was stable to the Alder-ene conditions. Extensive solvent studies were performed to determine the best conditions for the one-pot procedure. 

While the transition metal-catalyzed Alder-ene reaction has been developed to offer excellent regio- and chemos-electivity, stereoselective variants have only recently begun to appear in the literature.58 The scope and limitations of many of these protocols have yet to be established. Nonetheless, several groups have published exciting examples of asymmetric Alder-ene cyclizations. 

One of the major advantages of the rhodium(I)-catalyzed Alder-ene reaction is that mild conditions are used to effect the cycloisomerization process thus increasing the likelihood of being able to facilitate an asymmetric reaction. In fact, Zhang has demonstrated convincingly that the Alder-ene reaction of enynes can indeed be performed with excellent enantioselectivity and with similar efficiency. These examples are highlighted below in chronological order. 

Asymmetric 1,4-addition reactions, boron reagents, 10, 388 Asymmetric Alder-ene reactions, characteristics, 10, 579 Asymmetric alkoxycarbonylation, characteristics, 11, 467 Asymmetric alkylations, with alkylzincs, 2, 403 Asymmetric allylation... 

As variations of Rh-catalyzed cycloisomerization Widenhoefer and coworkers have developed asymmetric 1,6-enyne cyclization/hydrosilylation reactions by using the Rh(I)/biphemp system excellent de and ee were obtained [42]. Brum-mond et al. also discovered a rhodium(I)-catalyzed allenic Alder-ene reaction that... 

These reactions were, of course, limited to instances in which the enophile could be activated with a Lewis acid. Nevertheless, this was an excellent advancement toward promoting the utility of the Alder-Ene reaction and an asymmetric, Lewis acid-promoted ene reaction was reported by Whitesell using a chiral auxiliary. ... 

Asymmetric Alder-Ene reactions have been accomplished using optically-enriched starting materials, chiral auxiliaries, and chiral catalysts. The use of chiral catalysts has been applied to both chiral Lewis acid catalysis and asymmetric catalysis with chiral ligands. Some of these examples have already been cited for example, the use of a chiral auxiliary or optically-enriched substrates to generate optically-enriched products (LA catalysis with chiral auxiliary 30 + 31 -+ 32 or with optically-enriched starting materials 75 or 77 — 76 or 78, respectively or chiral LA applied to desymmetrization 33 + 34 — 35). More recent examples are displayed here, in particular, the use of chiral catalysts. 

An asymmetric and catalytic Conia-type Alder-Ene reaction has been reported using a combination of asymmetric Pd ligand [(DTBM-SEGPHOS)Pd(OTf)2, 171] and Yb(OT 3 with AcOH. The reactions are quite dilute, yet both conversion and optical purity were good for the p-keto ester or differentiated p-diketone substrates 172. 

Asymmetric Oiels-Alder reaction, ene reaction, hydrogenation, halogenatlon by means of chiral olelln, such as camphor derivative 1 or 2. 

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 ene reaction of fuUerene (C o) with 3-methylene-2,3-dihydrofuran gives an easily isolated addition product in good yield <96JOC2559>. There is a continuous need for chiral acrylate esters for asymmetric Diels-Alder reactions with high diastereoselectivity. Lewis acid promoted Diels-Alder reactions of acrylate esters from monobenzylated isosorbide 28 (or isomannide) and cyclopentadiene provided exclusively e db-adducts with good yields and high diastereoselectivity <96TL7023>. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Zhang s group has reported highly enantioselective cycloisomerization processes catalyzed by rhodium(i) chiral complexes (Scheme 53). For instance, (A)-BINAP gives excellent asymmetric induction in the reaction of enediyne 212 to furnish the quasi-enantiopure Alder-ene product 213.219... 

The carbonyl group in a ketone or aldehyde is an extremely versatile vehicle for the introduction of functionality. Reaction can occur at the carbonyl carbon atom using the carbonyl group as an electrophile or through enolate formation upon removal of an acidic proton at the adjacent carbon atom. Although the carbonyl group is an integral part of the nucleophile, a carbonyl compound can also be considered as an enophile when involved in an asymmetric carbonyl-ene reaction or dienophile in an asymmetric hetero Diels-Alder reaction. These two types of reaction are discussed in the next three chapters. 

Reactions where NLE have been discovered include Sharpless asymmetric epoxi-dation of allylic alcohols, enantioselective oxidation of sulfides to sulfoxides, Diels-Alder and hetero-Diels-Alder reactions, carbonyl-ene reactions, addition of MesSiCN or organometallics on aldehydes, conjugated additions of organometal-lics on enones, enantioselective hydrogenations, copolymerization, and the Henry reaction. Because of the diversity of the reactions, it is more convenient to classify the examples according to the types of catalyst involved. 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

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