A Powerful Hydrogen‐Bond‐Donating Organocatalyst for the Enantioselective Intramolecular Oxa‐Michael Reaction of α,β‐Unsaturated Amides and Esters

Kobayashi, Yusuke; Taniguchi, Yamato; Hayama, Naomi; Inokuma, Takao; Takemoto, Yoshiji

doi:10.1002/anie.201305492

Cited by 114 publications

(41 citation statements)

References 78 publications

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“…A fascinating construction of the C-7 amino-drivatized atorvastatin lateral-chain precursor was described recently by Kobayashi and coworkers [102]. In the initial synthetic step, they used a newly developed asymmetric intramolecular oxa-Michael reaction of an α,β-unsaturated amide derivative for the assembly of the C-5 amino-derivatized atorvastatin lateral-chain intermediate with one chiral center.…”

Section: Asn146 His143mentioning

confidence: 99%

Recent Progress in the Synthesis of Super-Statins

Časar

2015

Topics in Heterocyclic Chemistry

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Super-statins now represent a mature class of marketed drugs that faces the patent cliff, as has already occurred for fluvastatin and atorvastatin and is approaching for rosuvastatin and pitavastatin. However, they continue to trigger huge scientific interest in terms of their efficient preparation. This is not surprising, as easier accessibility of super-statins will promote even bigger demand in the market and consequently the need for higher rates of the production and productivity. Therefore, the stimulus for the development of even more efficient synthetic approaches to the heterocyclic moieties of super-statins and their chiral lateralchain precursors is at a peak, as also for the assembly of the these two parts into super-statins. The present report summarizes recent developments in the field of the synthesis of super-statins published from 2010 to 2015. Emphasis is given to the analysis of novel approaches to the formation of the chiral statin lateral chain, with detailed discussion of the development of new routes to respective heterocyclic cores and the assembly of these key units into the final super-statin structure.

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Section: Asn146 His143mentioning

confidence: 99%

Recent Progress in the Synthesis of Super-Statins

Časar

2015

Topics in Heterocyclic Chemistry

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“…Moreover, in the oxa-Michael adducts of a thioester or imide, there is the risk of racemization via retro-Michael/Michael addition during these transformations. Therefore, the direct AIOM addition to unactivated α,β-unsaturated esters [52][53][54][55][56] or amides [11] would be more desirable from the perspective of substrate availability and tolerance to racemization of products. However, such a reaction has received much less attention, likely because of the poor reactivity of both the Michael acceptor and the O-nucleophiles employed.…”

Section: The Intramolecular Oxa-michael Addition To αβ-Unsaturated Amentioning

confidence: 99%

“…So far, there have been only a few reports on the same reaction of α,β-unsaturated esters [52][53][54][55][56], and no reports with regard to α,β-unsaturated amides have yet been described. Recently we discovered that benzothiadiazine catalyst 3a effectively promoted the AIOM addition to α,β-unsaturated amides 23a-i (Table 11) [11]. A variety of dihydrobenzofurans 24a-g and chromans 24h-i were synthesized in good yields (68-99%) and high enantioselectivities (83-98% ee), with methyl, methoxy, nitro, and bromo groups being well tolerated under the reaction conditions.…”

Section: The Intramolecular Oxa-michael Addition Of Phenolsmentioning

confidence: 99%

Bifunctional Guanidines as Hydrogen-Bond-Donating Catalysts

Kobayashi

Takemoto

2015

Topics in Heterocyclic Chemistry

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Bicyclic guanidines, bearing 2-aminoquinazolin-4-one and 3-aminobenzothiadiazine-1,1-dioxide core structures, work as bifunctional amine catalysts, due to a double hydrogen-bond-donating ability of two guanidine N-H protons, which are capable of activating both nucleophile and electrophile simultaneously. In fact, these guanidine catalysts revealed to promote several asymmetric reactions such as hydrazination of active methylene compounds with azodicarboxylate and 1,3-proton migration of alkynoates to allenoates as well as the oxa-Michael addition and epoxidation of α,β-unsaturated amides and esters with better chemical yields and higher enantioselectivities than the corresponding thioureas. The catalytic mechanisms of these asymmetric reactions and their synthetic applications for biologically active molecules are also discussed in this chapter.

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“…5) However, simple α,β-unsaturated esters and amides have only been used in a limited number of successful studies because of their inherent low reactivity as Michael acceptors. 6,7) Instead, a variety of activated ester/amide surrogates possessing greater reactivity and rigidity, which enables them to interact with appropriate catalysts, have been developed for the Michael addition. 8) Recently, a range of activated carboxylates-specifically, α,β-unsaturated imides, 9,10) acyl pyrroles, 11) and acyl pyrazoles 12) -have been successfully applied in asymmetric metal-and organocatalyzed Michael additions to furnish the desired products with excellent enantioselectivity (Chart 1).…”

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confidence: 99%

Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

et al. 2016

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The first intermolecular asymmetric Michael addition of nitrogen-nucleophiles to α,β-unsaturated carboxylic acids was achieved through a new type of arylboronic acid equipped with chiral aminothiourea. The use of BnONH 2 as a nucleophile gives a range of enantioenriched β-(benzyloxy)amino acid derivatives in good yields and with high enantioselectivity (up to 90% yield, 97% enantiomeric excess (ee)). The obtained products are efficiently converted to optically active β-amino acid and 1,2-diamine derivatives.Key words aza-Michael addition; α,β-unsaturated carboxylic acid; integrated catalyst; thiourea; arylboronic acid; O-benzylhydroxylamine Stereoselective functionalization of electron-deficient alkenes continues to play a fundamental role in modern organic synthesis. The catalytic asymmetric aza-Michael addition of α,β-unsaturated carboxylic acid derivatives has been extensively investigated as a powerful protocol for the synthesis of optically active β-amino acids, [1][2][3][4] which are frequently encountered as important structural components in biologically active natural products and pharmaceuticals. 5) However, simple α,β-unsaturated esters and amides have only been used in a limited number of successful studies because of their inherent low reactivity as Michael acceptors.6,7) Instead, a variety of activated ester/amide surrogates possessing greater reactivity and rigidity, which enables them to interact with appropriate catalysts, have been developed for the Michael addition.8) Recently, a range of activated carboxylates-specifically, α,β-unsaturated imides, 9,10) acyl pyrroles, 11) and acyl pyrazoles 12) -have been successfully applied in asymmetric metal-and organocatalyzed Michael additions to furnish the desired products with excellent enantioselectivity (Chart 1). However, this masked ester/amide strategy requires a stoichiometric amount of an activating auxiliary and additional protection and deprotection steps. From the perspective of atom and step economy, achieving a direct Michael reaction of α,β-unsaturated carboxylic acids without the use of any activating templates is highly desirable. Despite strong synthetic utility, the direct Michael addition of α,β-unsaturated carboxylic acids has never been reported, except for an enzyme-catalyzed azaMichael addition 13,14) ; very few strategies have been exploited to catalytically activate the hydroxy group of carboxylic acids via transient covalent bond formation.By contrast, since the discovery by Yamamoto and Ishihara that electron-deficient arylboronic acids are efficient activators of carboxylic acids in direct amidation reactions, [15][16][17][18] 24,25) Hall reported that different types of arylboronic acids could be used for the cycloaddition of α,β-unsaturated carboxylic acids to dienes and 1,3-dipoles. 20,21) Recently, we also revealed that aminoarylboronic acid was the best catalyst for the intramolecular hetero-Michael addition of α,β-unsaturated carboxylic acids bearing sulfonamides or phenols.26) In addition, the asymmetric oxa-Michael ...

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A Powerful Hydrogen‐Bond‐Donating Organocatalyst for the Enantioselective Intramolecular Oxa‐Michael Reaction of α,β‐Unsaturated Amides and Esters

Cited by 114 publications

References 78 publications

Recent Progress in the Synthesis of Super-Statins

Recent Progress in the Synthesis of Super-Statins

Bifunctional Guanidines as Hydrogen-Bond-Donating Catalysts

Chiral Integrated Catalysts Composed of Bifunctional Thiourea and Arylboronic Acid: Asymmetric Aza-Michael Addition of α,β-Unsaturated Carboxylic Acids

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