Asymmetric O- and C-Alkylation of Phenols

and, Barry M. Trost; Toste, F. Dean

doi:10.1021/ja972453i

Cited by 216 publications

(121 citation statements)

References 18 publications

(27 reference statements)

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“…54) Thus, the ester 46 reacted with phenol 47 to provide the allyl phenyl ether 48 in good yield and ee (Eq. 20).…”

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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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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“…54) Thus, the ester 46 reacted with phenol 47 to provide the allyl phenyl ether 48 in good yield and ee (Eq. 20).…”

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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“…Enantioselective transition-metal-catalyzed allylic substitution [2][3][4][5][6] could be used to prepare these materials from achiral or racemic allylic electrophiles, but intermolecular enantioselective reactions of allylic acetates or carbonates with alkoxides are limited. Enantioselective reactions of phenoxides are well documented, [7][8][9] but no metal catalyzes intermolecular enantioselective allylations of alkoxides with broad scope. [10][11][12][13] Lee and Kim [14] as well as Evans and Leahy [15] demonstrated that zinc and copper alkoxides were more reactive for allylic substitution with achiral palladium and rhodium catalysts than alkali metal alkoxides.…”

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confidence: 99%

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

2004

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Elimination and racemization limit the synthesis of sterically hindered ethers, [1] such as a-chiral ethers, by the Willamson synthesis. Enantioselective transition-metal-catalyzed allylic substitution [2][3][4][5][6] could be used to prepare these materials from achiral or racemic allylic electrophiles, but intermolecular enantioselective reactions of allylic acetates or carbonates with alkoxides are limited. Enantioselective reactions of phenoxides are well documented, [7][8][9] but no metal catalyzes intermolecular enantioselective allylations of alkoxides with broad scope. [10][11][12][13] Lee and Kim [14] as well as Evans and Leahy [15] demonstrated that zinc and copper alkoxides were more reactive for allylic substitution with achiral palladium and rhodium catalysts than alkali metal alkoxides. The palladium-catalyzed reactions generated achiral ethers, but the rhodium-catalyzed reactions formed branched chiral ethers. Reactions of primary alkoxides with optically active allylic acetates occurred with predominant retention of configuration, but reactions of secondary and tertiary alkoxides were conducted with racemic allylic electrophiles. Because the products from reactions of primary alkoxides can be formed by alkylation of an optically active alcohol, but products from reactions of secondary alkoxides cannot, a catalyst that forms optically active products from hindered alkoxides and allylic carbonates is synthetically valuable. We report herein enantioselective reactions of primary, secondary, and tertiary alkoxides with achiral allylic carbonates to form branched chiral allylic ethers in high yields and with high stereoselectivity in the presence of an iridium catalyst containing a phosphoramidite ligand (Scheme 1). [16][17][18][19][20][21][22] To optimize the conditions for the allylation of aliphatic alkoxides with iridium-phosphoramidite catalysts, we studied the reactions of cinnamyl carbonate with benzyloxides (Table 1). Careful selection of carbonate, alkoxide counterion, and nitrogen substituents in the ligand was essential for high yields. Cinnamyl carbonates with small alkyl groups underwent transesterification in competition with etherification, but tert-butyl cinnamyl carbonate (1 a) provided the

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“…An eight-membered heterocycle fused to the aryl ring can be assembled by ring-closing metathesis of the diene 43, which would be prepared from the phenol 44. For the key construction of the tertiary stereogenic center at the benzylic position, we planned to use a substrate-controlled chirality transfer in the Claisen rearrangement 40,41) of the allyl aryl ether 45 prepared from the phenol 46 and S-(E)-1-(benzyloxy) pent-3-en-2-ol (47) by Mitsunobu coupling (Chart 5).…”

Section: Syntheses Of Helianane Sesquiterpenesmentioning

confidence: 99%

Stereocontrolled Total Synthesis of Natural Products with Characteristic Molecular Structures and Biological Activities

Shishido

2013

CHEMICAL & PHARMACEUTICAL BULLETIN

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Total synthetic studies on natural products with promising biological profiles, coupled with their intriguing structural features, are described. The target molecules dealt with in this article are five heliananetype sesquiterpenes (heliannuols A, D and K and heliespirones A and C) and three meroterpenes (breviones A, B and C) with allelopathic activity, as well as four cytotoxic polyketides (lasonolide A and aspergillides A, B and C) and two pyrrolidinoindoline alkaloids (physostigmine and psychotrimine) with acetylcholine esterase inhibitory and antibacterial activities.

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Asymmetric O- and C-Alkylation of Phenols

Cited by 216 publications

References 18 publications

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

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

Iridium‐Catalyzed Intermolecular Allylic Etherification with Aliphatic Alkoxides: Asymmetric Synthesis of Dihydropyrans and Dihydrofurans

Stereocontrolled Total Synthesis of Natural Products with Characteristic Molecular Structures and Biological Activities

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