(
 S
 )‐8a‐Methyl‐3,4,8,8a‐Tetrahydro‐1,6(2
 H
 , 7
 H
 )‐Naphthalenedione

Buchschacher, P.; Fürst, A.; Gutzwiller, J.

doi:10.1002/0471264180.os063.05

“…3). [3][4][5][6] The optically pure 6a can be obtained by a single recrystallization, and can be utilized for subsequent syntheses of many natural products. [7][8][9][10][11] However, the cyclization reaction of compounds with side chains other than a methyl group (e.g., allyl group 7b) was observed to have serious depreciation of the optical yield.…”

mentioning

confidence: 99%

The New Method for Introduction of an Allyl Group into the Angular Position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and Its Application to Chiral Wieland-Miescher Type Compound Synthesis

Hiroya

¹

,

Takahashi

²

,

Shimomae

³

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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Triterpenoid compounds are of interest because they occur widely in nature and have unique biological activities. Recently, Naganuma and his colleagues found that three natural triterpenes, betulin (1), uvaol (2), and soyasapogenol B (3), have reducing effects against the toxicity of cadmium chloride in HepG2 cells (Fig. 1). 1) They also reported that betulin induced certain proteins, though not metallothionein, which is the representative protein in reducing heavy metal toxicity. 1)To clarify the reduction mechanism of cadmium toxicity, we investigated the relationship between expression of activities and structures, with particular focus on the functional groups of betulin, using its analogues. The results showed that both the polar functional group, found at either the C3 or C28 positions, and the isopropenyl group play important roles in reducing cadmium toxicity and the cytotoxicity of betulin (1).2) However, it is difficult to carry out further investigation into the bioactivities of betulin because the only functional groups of this compound are hydroxyl and isopropenyl, both of which are crucial for its activity. Therefore, we decided to synthesize analogues of betulin, which could not be otherwise derived from natural products. Our synthetic strategy is summarized in Fig. 2, which shows the pentacyclic ring system being divided into two fragments: the AB fragment 4 and the DE fragment 5. Since our focus was on the angular substituents between the D and E rings, the starting material for 5 needed to be the optically pure bicyclo[4.4.0]decaline derivative 6b, and the starting material for 4 the Wieland-Miescher ketone 6a.The optically active Wieland-Miescher type bicyclic ketone 6a was effectively synthesized from the prochiral tricarbonyl compound 7a, using chiral proline as a chiral catalyst (Fig. 3).3-6) The optically pure 6a can be obtained by a single recrystallization, and can be utilized for subsequent syntheses of many natural products.7-11) However, the cyclization reaction of compounds with side chains other than a methyl group (e.g., allyl group 7b) was observed to have serious depreciation of the optical yield.12) In addition, proline did not work as a catalyst for this reaction, meaning a stoichiometric amount of proline is required to complete the reaction. If expensive synthetic proline has to be used, this presents a serious economic obstacle. Therefore, before starting the synthesis of the betulin analogues, it was decided to develop an efficient method for synthesizing optically pure bicyclo[4.4.0]decaline derivatives. Results and DiscussionThe essential features of the synthesis reaction are illustrated in Figs. 4 and 5. When the optically active diketone 8 was treated under acidic conditions, a mixture of the two diastereomers 9a and 9b resulted. However, by using an acidcatalyzed dehydration reaction, the mixture of 9a and 9b was converted to the single enantiomer 10. Using a dissolvingmetal reduction reaction with 10, it was expected that 11a The stereoselective introduction of an al...

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“…Both are active in water in a very selective way but with a limitation in the substrate scope. The use of small organic molecules to perform this reaction [30][31][32][33][34][35][36] gave the definitive boost for the development of organocatalysis, L-proline (1) and its derivatives being the most used systems to carry out this transformation in an intra- [37][38][39][40][41][42] or intermolecular fashion [43,45]. Although the use of this type of catalysts has several advantages, such as the atom economy enhancement, the use of mild reaction conditions and, more important, the lack of contamination with toxic metals of the final product, generally these organocatalytic systems are used in high loadings (from 10 to 30 mol%) and show their efficiencies in high polar solvents such as DMSO or DMF.…”

Section: Aqueous Aldol Reactions With Supported Organocatalystsmentioning

confidence: 99%

Pursuing Chemical Efficiency by Using Supported Organocatalysts for Asymmetric Reactions under Aqueous Conditions

Guillena

¹

,

Alonso²,

Baeza³

et al. 2015

COCAT

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Over the past decade, a great effort has been made by the chemical community to improve the efficiency and greenness of reactions. Merging the use of supported and recyclable organocatalysts and aqueous conditions to pursue this goal in the asymmetric synthesis of interesting enantioselective molecules lead to outstanding results in some cases. Progresses in this area also offer the possibility of having even more sustainable processes by implementing these reactions in the large scale production of chiral molecules using automated flow chemistry.

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“…

The decalin structure is found in bioactive molecules.W eh ave developed catalytic enantioselective formal (4+ +2) cycloaddition reactions via aldol-aldol cascade reactions between pyruvate-derived diketoester derivatives and cyclohexane-1,3-dione derivatives that affordh ighly functionalized decalin derivatives.The reactions were performed using aq uinidine-derived catalyst under mild conditions.D ecalin derivatives bearing up to six chiral carbon centers including tetrasubstituted carbon centers were synthesized with high diastereo-and enantioselectivities.F ive to six stereogenic centers were generated from achiral molecules with the formation of two C À Cb onds in as ingle transformation resulting in the formation of the decalin system. [2][3][4][5] Construction of the decalin ring system has been performed using cycloadditions, [2] cross coupling, [3] polyene cyclizations and related ene-involved annulations, [4] Robinson annulations [2c,d, 5] and related Michael-aldol reactions, [6] in which the reactions start from Michael additions to a,b-unsaturated ketones.H ere we report organocatalytic enantioselective aldol-aldol annulation cascade reactions to afford functionalized decalin derivatives (Scheme 1).In our strategy,C2symmetric starting materials pyruvatederived diketoester derivatives (dihydropyran derivatives) 1 [7] and cyclohexane-1,3-diones 2 are used for the aldol-aldol annulation cascade reactions to construct new cyclohexane rings,r esulting in the formation of decalin derivatives 3 or 4 (Scheme 1). [1] Decalin derivatives often have antiinflammatory,a nti-bacterial, and anti-tumor activities.

…”

mentioning

confidence: 99%

“…[1] Decalin derivatives often have antiinflammatory,a nti-bacterial, and anti-tumor activities. [2][3][4][5] Construction of the decalin ring system has been performed using cycloadditions, [2] cross coupling, [3] polyene cyclizations and related ene-involved annulations, [4] Robinson annulations [2c,d, 5] and related Michael-aldol reactions, [6] in which the reactions start from Michael additions to a,b-unsaturated ketones.H ere we report organocatalytic enantioselective aldol-aldol annulation cascade reactions to afford functionalized decalin derivatives (Scheme 1). [2][3][4][5] Construction of the decalin ring system has been performed using cycloadditions, [2] cross coupling, [3] polyene cyclizations and related ene-involved annulations, [4] Robinson annulations [2c,d, 5] and related Michael-aldol reactions, [6] in which the reactions start from Michael additions to a,b-unsaturated ketones.H ere we report organocatalytic enantioselective aldol-aldol annulation cascade reactions to afford functionalized decalin derivatives (Scheme 1).…”

mentioning

confidence: 99%

Catalytic Enantioselective Formal (4+2) Cycloaddition by Aldol–Aldol Annulation of Pyruvate Derivatives with Cyclohexane‐1,3‐Diones to Afford Functionalized Decalins

Chouthaiwale

¹

,

Aher

²

,

Tanaka

³

2018

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The decalin structure is found in bioactive molecules.W eh ave developed catalytic enantioselective formal (4+ +2) cycloaddition reactions via aldol-aldol cascade reactions between pyruvate-derived diketoester derivatives and cyclohexane-1,3-dione derivatives that affordh ighly functionalized decalin derivatives.The reactions were performed using aq uinidine-derived catalyst under mild conditions.D ecalin derivatives bearing up to six chiral carbon centers including tetrasubstituted carbon centers were synthesized with high diastereo-and enantioselectivities.F ive to six stereogenic centers were generated from achiral molecules with the formation of two C À Cb onds in as ingle transformation resulting in the formation of the decalin system. The decalin ring system is found in diterpenes,diterpenoids, steroids,a nd other bioactive natural products and related molecules ( Figure 1). [1] Decalin derivatives often have antiinflammatory,a nti-bacterial, and anti-tumor activities. [1] Therefore,s ynthesis of functionalized decalin derivatives is of interest in drug discovery efforts and in related research. [2][3][4][5] Construction of the decalin ring system has been performed using cycloadditions, [2] cross coupling, [3] polyene cyclizations and related ene-involved annulations, [4] Robinson annulations [2c,d, 5] and related Michael-aldol reactions, [6] in which the reactions start from Michael additions to a,b-unsaturated ketones.H ere we report organocatalytic enantioselective aldol-aldol annulation cascade reactions to afford functionalized decalin derivatives (Scheme 1).In our strategy,C2symmetric starting materials pyruvatederived diketoester derivatives (dihydropyran derivatives) 1 [7] and cyclohexane-1,3-diones 2 are used for the aldol-aldol annulation cascade reactions to construct new cyclohexane rings,r esulting in the formation of decalin derivatives 3 or 4 (Scheme 1). Ther eaction is expected to generate five or six stereogenic centers,d epending on the substituent of 2.W e hypothesized that appropriate catalysts and conditions would accelerate the reactions of 1 with 2 to afford decalin derivatives 3 and 4 with high diastereo-and enantioselectivities. [8] First, we searched for catalysts and conditions for the reaction of 1a and 2a to afford 3a.Selected results are shown in Table 1. Ther eaction in the presence of triethylamine afforded racemic product 3a in ag ood yield (entry 1). For enantioselective versions of the reaction, the use of (DHQD) 2 AQN [9] with tetraethylammonium bromide (TEAB) as additive in toluene-N-methyl-2-pyrrolidone (NMP) resulted in the formation of 3a in ag ood yield as as ingle diastereomer with high enantioselectivity (er 93:7, entry 4). Addition of TEAB improved the enantioselectivity (entry 2v ersus entry 3). Theu se of toluene-NMP as the solvent improved the solubility of 2a and resulted in faster reaction than the same reaction in toluene without affecting the enantioselectivity (entry 4v ersus entry 3). Theu se of three or more equivalents of 2a did not provide bette...

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( S )‐8a‐Methyl‐3,4,8,8a‐Tetrahydro‐1,6(2 H , 7 H )‐Naphthalenedione

Cited by 19 publications

References 14 publications

The New Method for Introduction of an Allyl Group into the Angular Position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and Its Application to Chiral Wieland-Miescher Type Compound Synthesis

The New Method for Introduction of an Allyl Group into the Angular Position of 2-(TBS-oxymethyl)-2,3,4,6,7,8-hexahydro-1-benzopyran-5-one and Its Application to Chiral Wieland-Miescher Type Compound Synthesis

Pursuing Chemical Efficiency by Using Supported Organocatalysts for Asymmetric Reactions under Aqueous Conditions

Catalytic Enantioselective Formal (4+2) Cycloaddition by Aldol–Aldol Annulation of Pyruvate Derivatives with Cyclohexane‐1,3‐Diones to Afford Functionalized Decalins

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