Regio- and diastereoselective conjugate addition of Grignard reagents to aryl substituted α,β-unsaturated carbonyl compounds derived from Oppolzer's sultam

Cao, Xiufang; Liu, Fang; Lu, Wenchang; Chen, Gang; Yu, Guang‐Ao; Liu, Sheng Hua

doi:10.1016/j.tet.2008.04.048

Cited by 24 publications

(19 citation statements)

References 39 publications

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“…(S)-3-Phenylheptan-1-ol: [31] Colorless oil; yield: 95 mg, 0. Sequential a-alkylation-desulfonation of bisA C H T U N G T R E N N U N G (sulfone) acetal adducts a-Alkylation of 14 a: NaH (120 mg 60 % in mineral oil) was placed in a flask and washed twice with dried hexane.…”

Section: Methodsmentioning

confidence: 99%

Catalytic Conjugate Additions of Geminal Bis(sulfone)s: Expanding the Chemistry of Sulfones as Simple Alkyl Anion Equivalents

Landa

Puente

Santos

et al. 2009

Chemistry A European J

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The value of cyclic gem-bis(sulfone) 4 as a simple alkyl nucleophile equivalent in catalytic C-C bond-forming reactions is demonstrated. The 1,4-type nucleophilic additions of bis(sulfone) 4 to alpha,beta-unsaturated ketones take place by assistance of catalytic guanidine base. On the other hand, pyrrolidines are able to catalyze the conjugate addition of 4 to both enones and enals, likely by means of iminium ion activation. Upon exploration of the best chiral pyrrolidine catalyst, it has been found that the addition of 4 to enals catalyzed by diphenylprolinol silyl ether 10 proceeds with very high enantioselectivity (beta-aryl-substituted enals >95% ee; beta-alkyl substituted enals up to 94% ee; ee = enantiomeric excess). Further reductive desulfonation of adducts gives rise to the corresponding beta-methyl aldehydes, as well as the derived alcohols, acetals, and methyl esters after simple (Mg, MeOH) well-established protocols. Application of the procedure to the synthesis of biologically relevant phenethyl building blocks is shown. Most interestingly, alpha-alkylation of initially obtained bis(sulfone) adducts can be done even with less reactive alkylating reagents, such as long linear-chain or branched-chain alkyl halides. Accordingly, upon the desulfonation process, a general, experimentally simple and highly enantioselective access to beta-branched aldehydes, alcohols, or esters is possible. Further exploration of the method includes the use of chiral alpha,beta-unsaturated aldehydes derived from citronellal as the Michael acceptor partners. In these instances, the sense of the conjugate addition of 4 is controlled by the chirality of the pyrrolidine catalyst, thus allowing for a stereochemically predictable access to 1,3-dimethyl arrays, such as those present in deoxygenated polyketide-type natural products. The intramolecular variation of this technology by using doubly unsaturated aldehyde-ester 22 illustrated the site selectivity of the procedure and its potential for tandem processes leading to highly substituted polycyclic systems, such as 24.

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Section: Methodsmentioning

confidence: 99%

Catalytic Conjugate Additions of Geminal Bis(sulfone)s: Expanding the Chemistry of Sulfones as Simple Alkyl Anion Equivalents

Landa

Puente

Santos

et al. 2009

Chemistry A European J

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“…Deprotonation of 1 with BuLi in THF, followed by monoalkylation with benzylic or allylic halides, or even with non-activated primary alkyl iodides, in the presence of hexamethylphosphoric triamide (HMPA) at À 788, followed by crystallization, gave products 2 in high yields and with high diastereomeric purities [19]. Non-destructive removal of the chiral auxiliary camphorsultam under mild conditions using NaBH 4 in aqueous THF furnished the sultam and the alcohols 3 [25], which were then brominated with HBr. The bromo derivatives 4 were then treated with 1H-1,2,4-triazole in MeCN in the presence of K 2 CO 3 at 60 -708 for 5 -7 h to give the chiral 1-(b-arylalkyl)-1H-1,2,4-triazoles 5 [26].…”

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confidence: 99%

“…layers were washed with brine (50 ml), concentrated, and purified by SiO 2 chromatography to afford the desired products 3, using 10% AcOEt/petroleum ether (60 -908) as an eluent. The enatiomeric products were prepared according to the same procedure [25]. .…”

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confidence: 99%

A Highly Enantioselective Access to Chiral 1‐(β‐Arylalkyl)‐1H‐1,2,4‐triazole Derivatives as Potential Agricultural Bactericides

Cao

et al. 2011

Chemistry & Biodiversity

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A series of chiral 1-(b-arylalkyl)-1H-1,2,4-triazole derivatives has been designed as potential antifungal agents. The target triazoles have been synthesized by using a chiral auxiliary as a controlling reagent. All of the compounds were obtained with high ee values, reaching up to 99%. Preliminary bioassay results have revealed that most of the synthesized compounds display significantly higher fungicidal activities against the species Fusarium oxysporium, Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii than the commercial agent triadimefon. Moreover, some of the enantiomers have been found to display significant differences in activity.

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“…Therefore, despite extensive research on the synthesis of chiral ketones, a generally convenient method to obtain b-substituted chiral ketones is still lacking. Recently, we have reported that the highly regioselective and diastereoselective conjugate addition of a series of Ar-substituted a,b-unsaturated carbonyl compounds with various Grignard reagents can be achieved by means of a chiral auxiliary [29]. Therefore, in view of our interest in new methods to construct chiral synthons, we would like to report herein a simple, catalyst-free, and direct formation of b-substituted chiral phenones via a nucleophilic cleavage reaction of corresponding N-alkanoylcamphorsultams with Ar-Grignard reagents (Scheme).…”

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confidence: 99%

“…-The synthesis and reaction conditions of the b-substituted chiral ketone derivatives 2a -2k are outlined in the Scheme. The key chiral substrates 1 were prepared following the methods outlined in the literature, and their spectral and analytical data were also identical to those stated in [29]. The chiral auxiliary attached to the carbonyl moiety in substrates 1 was then nucleophilically substituted by the aryl group on treatment with a Grignard reagent under optimized reaction conditions.…”

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confidence: 99%

Convenient Access to β‐Substituted Chiral Phenones

Cao

et al. 2009

Helvetica Chimica Acta

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A highly enantioselective approach towards the synthesis of b-substituted chiral ketones by utilizing Grignard reagents was achieved. The (R)-and (S)-antipodes of the target chiral ketones 2a -2k were obtained with up to 100% ee from chiral N-alkanoylcamphorsultams 1 (Scheme, Table 2). This simple, catalyst-free, direct procedure for the formation of chiral ketones is a fascinating method for the practical syntheses of chiral synthons as valuable building blocks and important medicinal intermediates.Introduction. -Optically active b-substituted ketones (b-chiral ketones) are common subunits in biologically active molecules. They are used as excellent building blocks, which have numerous applications in the enantioselective synthesis of natural products and important medicinal intermediates [1 -4]. In recent years, intensive investigations on the synthesis of b-substituted chiral ketones have been reported. For example, enantioselective metal-catalyzed types of the conjugate addition (CA) of organometallic reagents to enones have been extensively studied with Grignard [5] [6], dialkylzinc [7 -12], organocuprate, organoboron, alkyllithium, and silicon reagents [13 -18]. Most of these studies, however, involved the use of a catalytic or stoichiometric amount of chiral ligands. Recently, a novel transformation method from Weinreb amide to b-substituted chiral ketones has been developed [19 -23]. Weinreb amide could be further alkylated with Grignard reagents to give various ketone derivatives with C(b) as center of chirality. Simultaneously, Nagaos group studied how active monothioester derivatives can be converted to chiral ketones when treated with the Grignard reagent and metal-complex catalysts [24]. Furthermore, enzymatic transformations to obtain chiral ketones have also been reported [25 -28]. These include the hydrolysis of enol esters and baker-yeast-mediated asymmetric reduction of a,b-unsaturated carbonyl compounds. Nevertheless, almost all of the above-described synthetic methodologies for the synthesis of chiral ketones need expensive chiral ligands and metal catalysts, and the reaction conditions are rigorous (low temperature or long reaction time). Therefore, despite extensive research on the synthesis of chiral ketones, a generally convenient method to obtain b-substituted chiral ketones is still lacking. Recently, we have reported that the highly regioselective and diastereoselective conjugate addition of a series of Ar-substituted a,b-unsaturated carbonyl compounds with various Grignard reagents can be achieved by means of a chiral auxiliary [29]. Therefore, in view of our interest in new methods to construct chiral synthons, we would like to report herein a simple, catalyst-free, and direct formation of b-substituted chiral phenones via a nucleophilic cleavage reaction of corresponding N-alkanoylcamphorsultams with Ar-Grignard reagents (Scheme).

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Regio- and diastereoselective conjugate addition of Grignard reagents to aryl substituted α,β-unsaturated carbonyl compounds derived from Oppolzer's sultam

Cited by 24 publications

References 39 publications

Catalytic Conjugate Additions of Geminal Bis(sulfone)s: Expanding the Chemistry of Sulfones as Simple Alkyl Anion Equivalents

Catalytic Conjugate Additions of Geminal Bis(sulfone)s: Expanding the Chemistry of Sulfones as Simple Alkyl Anion Equivalents

A Highly Enantioselective Access to Chiral 1‐(β‐Arylalkyl)‐1H‐1,2,4‐triazole Derivatives as Potential Agricultural Bactericides

Convenient Access to β‐Substituted Chiral Phenones

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