The ester enolate Claisen rearrangement. Stereochemical control through stereoselective enolate formation

Ireland, Robert E.; Mueller, Richard H.; Willard, Alvin K.

doi:10.1021/ja00426a033

Cited by 831 publications

(257 citation statements)

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“…Thus, by using (R)-5a having a phenyl group on the chiral carbon, enantioselectivities of the reactions decrease as the bulkiness of the substituent on the 4-position of cyclohexanones increases (runs [1][2][3][4]. The same tendency is observed for the reactions using (R)-12a (runs 5-8), (R)-13a (runs 9-12), (R)-14a (runs [13][14][15][16], and (R)-15a (runs 17-19), having a 1-naphthyl, 2-naphthyl, 3,5-dimethylphenyl, and 3,5-di-tertbutylphenyl group, respectively, on the chiral carbon. It is also recognized that enantioselectivities of the reactions are generally higher by using chiral lithium amides having a phenyl or 1-naphthyl group on the chiral carbon ((R)-5a or (R)-12a), while they become lower by using chiral lithium amides having a more bulky substituent on the chiral carbon ((R)-14a, (R)-15a).…”

mentioning

confidence: 59%

“…[6][7][8][9][10][11][12][13][14][15] N-NMR spectra were recorded on a JEOL GSX-500 spectrometer (73.45 and 50.55 MHz,respectively) 5i) The following abbreviations are used: dϭdoublet, ddϭdoublet of doublets, tϭtriplet, ttϭtriplet of triplets. Optical rotations were measured by a JASCO DIP-360 or a JASCO DIP-370 digital polarimeter using benzene as a solvent.…”

Section: Methodsmentioning

confidence: 99%

“…2,13) However, since the dimer (18) is considered to be responsible for the reactions under the internal quench method or under the external quench conditions in the presence of LiCl, it is reasonable to assume that the eight-membered cyclic transition state model (19) including LiCl 14) is a better explanation for (R)-5a to give the products (3a-d) rich in R-enantiomer. By this transition state model, it is possible to explain the severe steric interactions between the bulkier aryl substituent of the chiral bidentate lithium amides and the bulkier 4-substituent of cyclohexanones to reduce enantioselectivities of the reactions.…”

Section: E)mentioning

confidence: 99%

“…The product of the reaction of 1d having a tert-butyl group by (R)-15b having a 3,5-di-tert-butylphenyl group is almost racemic 3d (run 20). Enantioselectivities of the reactions using (S)-16b (runs 21-24) are improved compared to those using (S)-16a (runs 21-24, Table 1), but are still lower than those using (R)-5b, (R)-12b, (R)-13b, and (R)-14b (runs [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16].…”

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confidence: 99%

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Stereoselective Reactions. XXXIV.<SUP>1)</SUP> Enantioselective Deprotonation of Prochiral 4-Substituted Cyclohexanones Using Chiral Bidentate Lithium Amides Having a Bulky Group Instead of a Phenyl Group on the Chiral Carbon

Toriyama

Sugasawa²,

Motohashi

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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Lithium dialkylamides such as lithium diisopropylamide (LDA) are widely used in organic synthesis as strong bases with low nucleophilicity.2) We have previously reported enantioselective deprotonation 3) of prochiral 4-substituted cyclohexanones (1) using chiral lithium amides in the presence of excess trimethylsilyl chloride (TMSCl) (Corey's internal quench method 4) ) to isolate the corresponding lithium enolates (2) as trimethylsilyl enol ethers (3). 5) Among various chiral lithium amides examined, chiral bidentate lithium amides ((R)-5a, (R)-5b) having a phenyl group on the chiral carbon, a neopentyl or trifluoroethyl group on the amide nitrogen, and a piperidino group as an internal ligation site for the lithium give the products ((R)-3) in high ee's. 5b,c,i,l) By Xray and NMR studies, it is shown that these chiral lithium amides ((R)-5a, (R)-5b) exist almost entirely as a chelated monomeric form ((R)-6) having a chiral amide nitrogen in tetrahydrofuran (THF) or dimethoxyethane (DME), and in THF, DME, ether, or toluene in the presence of 2 eq of hexamethylphosphoric triamide (HMPA). 5b,c,i,l) In this structure, the substituent (a neopentyl or trifluoroethyl group) on the amide nitrogen and the phenyl group on the chiral carbon are trans, presumably due to the steric repulsion between them. It is therefore reasonable to assume that bidentate chiral lithium amides ((R)-12a, b-(R)-15a, b, (S)-16a, b) having a bulkier substituent instead of a phenyl group on the chiral carbon would be more effective as chiral bases for enantioselective deprotonation. Based on this consideration, we prepared chiral bidentate amines ((R)-7a, b-(R)-10a, b, (S)-11a, b) for the preparation of their corresponding lithium amides.1) The present paper describes the results of deprotonation reactions of 4-substituted cyclohexanones (1a-d) by these chiral bidentate lithium amides.The reactions of 1a-d were carried out under the fixed conditions, using 1.2 eq of lithium amide and 5 eq of TMSCl in the presence of 1.2 eq of HMPA in THF at Ϫ78°C for 30 min.6) The results using chiral lithium amides ((R)-5a, (R)-11a-(R)-15a, and (S)-16a) having a neopentyl group on the amide nitrogen are summarized in Table 1. It is shown that, except one case (run 20), chiral lithium amides having R-configuration give the products rich in R-enantiomer, while that having S-configuration gives the products rich in S-enantiomer. It is also shown that the enantioselectivities of the reactions are dependent on the bulkiness of both the substituent on the chiral carbon of the chiral lithium amides and the sub- * To whom correspondence should be addressed. e-mail: kkoga@ms.aist-nara.ac. Narashinodai, Funabashi-shi, Chiba 274-8555, Japan, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., b 21 Miyukigaoka, Tsukuba-shi, Ibaraki 305-8585, Japan, and Research and Education Center for Materials Science, Nara Institute of Science and Technology, c Takayama-cho, Ikomashi, Nara 630-0101, Japan. Received January 5, 2001; accepted February 1, 20...

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mentioning

confidence: 59%

Section: Methodsmentioning

confidence: 99%

Section: E)mentioning

confidence: 99%

mentioning

confidence: 99%

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Stereoselective Reactions. XXXIV.<SUP>1)</SUP> Enantioselective Deprotonation of Prochiral 4-Substituted Cyclohexanones Using Chiral Bidentate Lithium Amides Having a Bulky Group Instead of a Phenyl Group on the Chiral Carbon

Toriyama

Sugasawa²,

Motohashi

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…at −78 °C in anhydrous tetrahydrofuran, followed by a conventional operation. A proposed mechanism according to Ireland-Claisen rearrangement was outlined in Scheme 3 [29]. The formation of preferential configuration of the (E)-silyl enol ether could help to rationalize the possible six-membered, acyclically advantage chair-like transition state.…”

Section: Resultsmentioning

confidence: 99%

Construction of the 1,2-Dialkenylcyclohexane Framework via Ireland-Claisen Rearrangement and Intramolecular Barbier Reaction: Application to the Synthesis of (±)-Geijerone and a Diastereoisomeric Mixture with Its 5-Epimer

et al. 2014

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Abstract:The elemene-type terpenoids, which possess various biological activities, contain a syn-or anti-1,2-dialkenylcyclohexane framework. An efficient synthetic route to the syn-and anti-1,2-dialkenylcyclohexane core and its application in the synthesis of (±)-geijerone and its diastereomer is reported. Construction of the syn-and anti-1,2-dialkenyl moiety was achieved via Ireland-Claisen rearrangement of the (E)-allylic ester, and the cyclohexanone moiety was derived from the iodoaldehyde via intramolecular Barbier reaction. The synthetic strategy allows rapid access to various epimers and analogues of elemene-type products.

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Eine neue Variante der Claisen-Umlagerung von aus Allylmalonaten abgeleiteten Trimethylsilylketenacetalen – effiziente, hoch enantio- und diastereoselektive Synthesen von (+)-Methyldihydroepijasmonat und (+)-Methylepijasmonat

Fehr¹,

Galindo

2000

Angewandte Chemie

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Mit vollständiger Chiralitätsübertragung verläuft die Claisen‐Umlagerung der Trimethylsilyl(TMS)‐Ketenacetale, die aus den Allylmalonaten (R)‐1 (R=Pentyl, 2‐(Z)‐Pentenyl) hergestellt wurden. Diese sind ihrerseits durch enantioselektive Reduktion/Veresterung oder durch enzymatische kinetische Racematspaltung zugänglich. Die cis‐Konfiguration in (+)‐3 wurde durch eine hoch syn‐selektive Epoxidierung von (+)‐2 und eine anschließende suprafaciale 1,2‐H‐Wanderung sichergestellt.

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The ester enolate Claisen rearrangement. Stereochemical control through stereoselective enolate formation

Cited by 831 publications

References 9 publications

Stereoselective Reactions. XXXIV.<SUP>1)</SUP> Enantioselective Deprotonation of Prochiral 4-Substituted Cyclohexanones Using Chiral Bidentate Lithium Amides Having a Bulky Group Instead of a Phenyl Group on the Chiral Carbon

Stereoselective Reactions. XXXIV.<SUP>1)</SUP> Enantioselective Deprotonation of Prochiral 4-Substituted Cyclohexanones Using Chiral Bidentate Lithium Amides Having a Bulky Group Instead of a Phenyl Group on the Chiral Carbon

Construction of the 1,2-Dialkenylcyclohexane Framework via Ireland-Claisen Rearrangement and Intramolecular Barbier Reaction: Application to the Synthesis of (±)-Geijerone and a Diastereoisomeric Mixture with Its 5-Epimer

Eine neue Variante der Claisen-Umlagerung von aus Allylmalonaten abgeleiteten Trimethylsilylketenacetalen – effiziente, hoch enantio- und diastereoselektive Synthesen von (+)-Methyldihydroepijasmonat und (+)-Methylepijasmonat

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