Asymmetric one-pot Robinson annulations

Rajagopal, D.; Narayanan, R; Swaminathan, S.

doi:10.1016/s0040-4039(01)00733-x

Cited by 51 publications

(40 citation statements)

References 7 publications

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“…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

Takahashi

Shimomae

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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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

Takahashi

Shimomae

et al. 2005

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…60 This was applied in one-pot procedure for the synthesis of spiroenediones, but yields and ee's are still moderate. 61 This annulation procedure was extended to other polyketones for the syntheses of taxol, 62 steroid analogs, 63 antibiotic, 64 and antimalarial agents. 65 Chiral triketoacetonides can be converted to the corresponding bicyclic enediones with good levels of diastereoselectivity, albeit in moderate conversion ratios.…”

Section: First Updatementioning

confidence: 99%

(S)-Proline

Wallbaum

Martens

Minassian

et al. 2016

Encyclopedia of Reagents for Organic Synthesis

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“…6 Recently, extensions of this chemistry have been published and much more selective organocatalysts have been developed. [68][69][70][71] The combination of proline-catalyzed aldol reactions with other methods of forming carbon-carbon bonds leads to a versatile strategy for multi-component condensation: with Knoevenagel, 72 with self-aldol, 73 with aldehyde α-amination, 74 and with Knoevenagel-reduction. 75…”

Section: Aldol-related Reactionsmentioning

confidence: 99%

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

Kotsuki¹,

Ikishima²,

Okuyama³

2008

HETEROCYCLES

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-Organocatalytic asymmetric synthesis has been extensively studied and several important procedures for preparing optically active organic compounds have been developed. Research in this area has progressed rapidly in the last ten years. This review addresses the most significant advances in asymmetric synthesis using proline and related chiral organocatalysts mainly focusing on aldol reactions from the viewpoint of synthetic interests. This includes (1) proline-catalyzed aldol reactions, (2) proline-related chiral catalysts, and (3) other types of amino acid catalysts.

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Asymmetric one-pot Robinson annulations

Cited by 51 publications

References 7 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

(S)-Proline

Organocatalytic Asymmetric Synthesis Using Proline and Related Molecules. Part 2.

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