Catalytic Asymmetric Synthesis. Группа авторов

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СКАЧАТЬ 2006, Enders reported a seminal paper on organocatalyst‐mediated domino reaction (Eq. 1.27) [53]. He reported an excellent domino reaction catalyzed by diphenylprolinol silyl ether, wherein three reactions such as Michael/Michael/intramolecular aldol condensation reactions take place in one pot to provide cyclohexene carbaldehydes bearing four stereogenic centers with excellent stereocontrol. Rather complex skeletons were synthesized only by mixing the substrates via a domino reaction.

Enders’ group reported many useful domino reactions [54]. For instance, functionalized complex tricyclic polyethers were synthesized by one‐pot quadruple domino oxa‐Michael/Michael/Michael/aldol condensation/hetero‐Diels‐Alder reaction in nearly enantiomerically pure form (Eq. 1.28) [55]. Tetracyclic pyridocarbazole derivatives were synthesized by the three‐component triple cascade reaction such as Diels‐Alder/aza‐Michael/intramolecular aldol condensation reactions with excellent enantioselectivity (Eq. 1.29) [56].

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1.6. DOMINO REACTION AND TOTAL SYNTHESIS

      Many domino reactions have been developed that use organocatalysts. Domino reaction catalyzed by organocatalysts can generate complex structures in a single reaction vessel. This is a very powerful method for the synthesis of natural products and drugs [57]. Organocatalytic domino reactions have been successfully applied to natural product synthesis. In this section, selected domino reactions will be described with an application to total synthesis.

      1.6.1. Steroid Skeleton

Hong reported the synthesis of a steroid skeleton by a one‐pot reaction starting from an α,β‐unsaturated aldehyde and a nitroalkane (Eq. 1.30). A domino Michael/Michael reaction proceeded, followed by aldol and Henry reaction in a one‐pot operation, to afford a steroid skeleton with excellent enantioselectivity [58].

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      1.6.2. α‐Skytanthine and Quinine

Ishikawa reported a domino Michael reaction/hemiacetal formation/dehydration for the synthesis of C4‐alkyl substituted chiral piperidines using diphenylprolinol silyl ether (Eq. 1.31) [59]. This is a formal aza [3+3] cycloaddition reaction with aliphatic α,β‐unsaturated aldehydes and thioamide derivatives. Thioamide is a reactive nucleophile. The reaction proceeded efficiently, and only 0.1 mol % catalyst loading is sufficient for a multigram‐scale synthesis to complete within a suitable reaction time. This reaction was applied to the total synthesis of several alkaloids such as α‐skytanthine [59a] and quinine [59b].

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      1.6.3. (+)‐Lycoposerramine Z

Bradshaw and Bonjoch reported a domino Michael/aldol (Robinson annulation)/aza‐Michael reaction to afford a substituted decahydroquinoline with a high diastereo‐ and enantioselectivity in a one‐pot operation (Eq. 1.32). (+)‐Lycoposerramine Z was synthesized from this intermediate [60].

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      1.6.4. Estradiol Methyl Ether

Bicyclo[4.3.0]none derivatives, which are C and D rings of the steroids, were synthesized as a single isomer with excellent enantioselectivity by diphenylprolinol silyl ether mediated Michael reaction of nitroalkane possessing a diketone moiety and an α,β‐unsaturated aldehyde, followed by aldol reaction (Eq. 1.33). This domino reaction was used as a key reaction for the total synthesis of estradiol methyl ether, which was synthesized using five reaction vessels with four purifications [61].

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      1.6.5. MacMillan’s Alkaloid Synthesis

MacMillan reported the domino Diels‐Alder reaction/β‐elimination of methyl selenide/aza‐Michael reaction to afford a spiroindoline intermediate (Eq. 1.34). The first Diels‐Alder reaction and the third aza‐Michael reaction were catalyzed by the same MacMillan’s catalyst via an iminium ion as an intermediate, and an excellent enantioselectivity was obtained. From the intermediate, (‐)‐strychnine, (‐)‐akuamicine, (+)‐aspidospermidine, (+)‐vincadifformine, (‐)‐kopsinine, and (‐)‐kopsanone were synthesized efficiently [62].

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      1.6.6. Prostaglandin E₁ Methyl Ester

A domino Michael/Henry reaction of succinaldehyde and nitroalkene in the presence of diphenylprolinol silyl ether proceeded to afford substituted cyclopentanecarbaldehyde, which was further treated with Horner‐Wadsworth‐Emmons reagent to provide a cyclopentane derivative with excellent enantioselectivity in a one‐pot operation (Eq. 1.35). This is a key intermediate for the synthesis of prostaglandin E₁ methyl ester, which was synthesized using a total of three reaction vessels [63].

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      1.6.7. Corey Lactone

Nonactivated ketones are useful Michael СКАЧАТЬ