Asymmetric induction in allylic alkylations of 3-(acyloxy)cycloalkenes

Trost, Barry M.; Bunt, Richard C.

doi:10.1021/ja00088a059

Cited by 259 publications

(152 citation statements)

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“…46) Cyclic substrates are generally excellent with broad ranges of nucleophiles including carbon, sulfur, nitrogen, and oxygen. 47) Illustrative of carbon nucleophiles is the DYKAT of 3-acyloxycycloheptene with malonate (Eq. 16, path a) 47) and nitroalkanes (Eq.…”

Section: Type C Enantiodiscriminationmentioning

confidence: 99%

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Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Trost

2002

Chem. Pharm. Bull.

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307

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Chiral compounds have many applications. None are more important than those related to biological targets. The chiral nature of biological receptors make chiral ligands common objectives as pharmaceuticals and agrichemicals. Thus, developing efficient synthetic methods to such compounds represents an important challenge. In spite of great advances, resolution methods still frequently represent the most economical method for commercial production in spite of the fact that the theoretical yield of the single desired enantiomer cannot exceed 50% unless the opposite enantiomer can be converted to the desired one. Using starting materials from the chiral pool also constitutes a common strategy. More recently, attention has shifted to inducing chirality into achiral precursors. Two tacts have been explored. In one, chiral auxiliaries, normally emanating from the chiral pool, are covalently attached to prochiral substrates.1) The advantage of this approach is the high degree of success in transmitting chiral information in this more controlled strategy. However, it suffers from numerous drawbacks. First, it requires stoichiometric amounts of the chiral auxiliary which ultimately is not part of the final product. It also requires additional steps to add and subsequently remove the chiral auxiliary. Clearly, the conceptually most attractive strategy is employing asymmetric catalytic reactions. 2)Some of these have achieved great success. Two of the most successful have been asymmetric catalytic hydrogenation and asymmetric catalytic oxidation of alkenes, notably epoxidation. These two reactions, in addition to virtually every other asymmetric catalytic reaction, share a common feature-the enantiodiscriminating event involves recognizing the enantiotopic faces of a prochiral p-unsaturation such as a carbonyl group or a double bond. Furthermore, each of these reactions also involve formation of just one bond type-a C-H bond in the case of hydrogenation and a C-O bond in the case of oxidation.Catalytic asymmetric allylic alkylation differs from virtually all other catalytic processes in two important ways. In the first, there are many enantiodiscriminating mechanisms, not just one. As shown in Fig. 1, there are at least five such mechanisms. As in most other catalytic asymmetric reactions, differentiating the enantiotopic faces of a p-unsaturation is one mechanism (Fig. 1, A). A second mechanism is differentiating enantiopic leaving groups (Fig. 1, B). Mechanism C involves differentiating enantiotopic termini of a pallylmetal intermediate. Since this intermediate derives from a chiral racemic precursor in which the chirality of the substrate is lost, this deracemization constitutes a dynamic kinetic asymmetric transformation (DYKAT). Mechanism D is a varient of mechanism A wherein the p-allylmetal intermediates interconvert faster than they are attacked by a nucleophile and asymmetric induction derives from differential rates of reaction of the two diastereomeric intermediates. This mechanism allows employment of either an ...

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Section: Type C Enantiodiscriminationmentioning

confidence: 99%

“…47) Illustrative of carbon nucleophiles is the DYKAT of 3-acyloxycycloheptene with malonate (Eq. 16, path a) 47) and nitroalkanes (Eq. 16, path b).…”

Section: Type C Enantiodiscriminationmentioning

confidence: 99%

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Trost

2002

Chem. Pharm. Bull.

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307

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“…It is to be noted that when 5 was used as the ligand, the reaction was again very sluggish, only 18% conversion being observed after 24 h (Table 1, entry 10). Lower conversion was obtained when the alkylation reaction using 4 as the ligand was performed in THF in the presence of (C 6 H 13 ) 4 NBr, 11 the enantioselectivity being 28% (Table 1, entry 7). However the use of CH 2 Cl 2 as the solvent in the presence of (C 6 H 13 ) 4 NBr gave a quantitative conversion, with an enantioselectivity up to 19% ; when the reaction was performed at 0 °C, the conversion was 63% and the enantioselectivity increased to 53% ( Finally we used potassium phthalimide as a nitrogen nucleophile.…”

Section: Resultsmentioning

confidence: 99%

“…3 A variety of analogues containing anthracenyl, diphenyl, tartrate, or sugar-derived chiral scaffolds have been prepared in order to study the structural and electronic aspects of the ligand in different reactions. [6][7][8][9][10] However to our knowledge there is no study concerning the preparation of such ligands containing an aromatic heterocycle instead of a phenyl ring. We present in this paper the preparation of two ligands 4 and 5, bearing an aromatic heterocycle, and give some preliminary results in the use of these ligands in asymmetric alkylation.…”

Section: Introductionmentioning

confidence: 99%

Heterocyclic Trost’s ligands. Synthesis and applications in asymmetric allylic alkylation

Sinou

Percina-Pichon²,

Konovets³

et al. 2004

Arkivoc

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Condensation of (1R,2R)-1,2-diaminocyclohexane with 2-(diphenylphosphino)nicotinic acid and 3-(diphenylphosphino)quinoxaline-2-carboxylic acid afforded the corresponding diphosphines. These ligands were used in the palladium-catalyzed alkylation of various allylic acetates with carbon and nitrogen nucleophiles, giving generally lower enantioselectivities than the analogous non-heterocyclic ligands.

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“…While the metal-catalyzed π-allyl substitution for the synthesis of allylic amines (Scheme 1, expression 5) is restricted by the same issues mentioned above (16,17), the 1,2-addition of vinylic metal species to imines (Scheme 1, expression 4) often applies an additional chiral auxiliary attached to the nitrogen atom in order to obtain high stereocontrol (9). An efficient transformation with complete stereoinversion, is the Mitsunobu reaction (Scheme 1, expression 6) which has been applied numerous times for the synthesis of optically active allylic amines (18).…”

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confidence: 99%

Simple strategy for synthesis of optically active allylic alcohols and amines by using enantioselective organocatalysis

Jiang

Holub

Jørgensen

2010

Proc. Natl. Acad. Sci. U.S.A.

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A simple organocatalytic one-pot protocol for the construction of optically active allylic alcohols and amines using readily available reactants and catalyst is presented. The described reaction is enabled by an enantioselective enone epoxidation/aziridinationWharton-reaction sequence affording two highly privileged and synthetically important classes of compounds in an easy and benign way. The advantages of the described sequence include easy generation of stereogenic allylic centers, also including quaternary stereocenters, with excellent enantio-and diastereomeric-control and high product diversity. Furthermore, using monosubstituted enones as substrates, having moderate enantiomeric excess, the one-pot reaction sequence proceeds with an enantioenrichment of the products and high diastereoselectivity was achieved.asymmetric catalysis | allylic amines | enantioselectivity A llylic alcohols and amines represent two of the most abundant and fundamental building blocks in contemporary organic synthesis. The possible transformations of these important compounds are numerous and proceed often with excellent stereoinduction (1-3). Consequently, optically active allylic alcohols and amines have appeared innumerable times as key intermediates in asymmetric total syntheses, showing the need for efficient and benign methods of their formation.One of the traditional synthetic approaches to optically active allylic alcohols is the catalytic kinetic resolution applying enzymes (4). In addition, Sharpless and coworkers have successfully established an asymmetric titanium-catalyzed resolution of racemic secondary allylic alcohols via the Sharpless-Katsuki epoxidation (5), resulting in a mixture of epoxy-alcohols and optically active allylic alcohols (Scheme 1, expression 1). However, the fact that the resolution method is restricted to a theoretical yield of 50%, makes other direct routes to optically active allylic alcohols highly desirable. With the dynamic kinetic resolution (6), a procedure that allows full conversion of the starting compound to one desired product with excellent stereocontrol was established. In this process, a fast and efficient in situ racemization reaction of the undesired enantiomer of the starting material is the key to overcome the 50%-yield limit of the traditional resolution method. However, the scope of this reaction is limited to mainly acyclic substrates and the combined use of transition metal and enzyme is necessary (Scheme 1, expression 2).As an alternative to the resolution method, several different enantioselective reduction protocols of enones have been developed. Examples are the Corey-Bakshi-Shibata reduction (7), applying a borane-prolinol complex, and the catalytic enantioselective hydrogenation, applying BINAP [2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl]-diamine ruthenium complexes developed by Noyori and coworkers (8) (Scheme 1, expression 3). The needs of bulky functional groups, different substitution patterns at the enone functionality, and inert reaction conditions for obtain...

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Asymmetric induction in allylic alkylations of 3-(acyloxy)cycloalkenes

Cited by 259 publications

References 1 publication

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Pd Asymmetric Allylic Alkylation (AAA). A Powerful Synthetic Tool.

Heterocyclic Trost’s ligands. Synthesis and applications in asymmetric allylic alkylation

Simple strategy for synthesis of optically active allylic alcohols and amines by using enantioselective organocatalysis

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