Synthesis of Naturally Occurring Tropones and Tropolones

Abstract

Tropones and tropolones are an important class of seven-membered non-benzenoid aromatic compounds. They can be prepared directly by oxidation of seven-membered rings. They can also be derived from cyclization or cycloaddition of appropriate precursors followed by elimination or rearrangement. This review discusses the types of naturally occurring tropones and tropolones and outlines important methods developed for the synthesis of tropone and tropolone natural products.

Scheme 1

Tropones, tropolones and related compounds

Scheme 2

Tropolones discovered in early days

Scheme 3

Examples of mono- and bicyclic naturally occurring tropones and related compounds

Scheme 4

Norditerpene tropones

Scheme 5

Examples of benzotropolones and some theaflavin derivatives

Scheme 6

Tropoisoquinolines and tropoloisoquinolines

Scheme 7

Colchicine and its congeners

Scheme 8

Biomimetic synthesis of benzotropolones

Scheme 9

Biomimetic synthesis of crocipodin and theaflavin

Scheme 10

Oxidation of 1,2-cycloheptanedione and 2-hydroxycycloheptanone by bromine and NBS

Scheme 11

Oxidation of cycloheptanone to tropone by Br₂

Scheme 12

Oxidation of cycloheptatriene by permanganate

Scheme 13

Synthesis of tropone via ditropyl ether

Scheme 14

Synthesis of tropone from tropylium ion

Scheme 15

Synthesis of tropone by electrochemical oxidation

Scheme 16

Synthesis of tropone by SeO₂ oxidation

Scheme 17

Synthesis of tropones from endoperoxides

Scheme 18

Oxidation of benzotropone to benzotropolone

Scheme 19

Dehydrogenative oxidation by hypervalent iodine reagents

Scheme 20

Synthesis of β-thujaplicin and dolabrin

Scheme 21

Synthesis of dolabrin from β-thujaplicin

Scheme 22

Formal synthesis of colchicine from purpurogallin

Scheme 23

Synthesis of (±)-colchicine from acycloheptanone

Scheme 24

Synthesis of thujaplicin by electro-reductive alkylation of substituted cycloheptatrienes

Scheme 25

Synthesis of nezukone via cyclization

Scheme 26

Synthesis of (±)-colchicine by acyloin cyclization

Scheme 27

Formal synthesis of colchicine derivative by cyclization of a cycloheptatriene

Scheme 28

Woodward’s synthesis of (±)-colchicine

Scheme 29

Divergent regioselective synthesis of thujaplicins

Scheme 30

Synthesis of salviolone by double aldol condensation

Scheme 31

Synthesis of taxamairin B by Friedel-Crafts acylation

Scheme 32

Formal synthesis of colchicine by dienyne metathesis

Scheme 33

Synthesis of 3,4-benzotropolones by ring-closing metathesis

Scheme 34

Synthesis of stipitatic acid using Buchner reaction

Scheme 35

Mander’s synthesis of (±)-hainanolidol

Scheme 36

Balci’s synthesis of isomers of stipitatic acid esters

Scheme 37

Eschenmoser’s synthesis of (±)-colchicine

Scheme 38

Intramolecular radical cyclization of phenolic nitronates developed by Kende

Scheme 39

Cha’s synthesis of pareitropone

Scheme 40

Tobinaga’s formal synthesis of (±)-colchicine

Scheme 41

Synthesis of monocyclic tropolones via Simmons-Smith cyclopropanation and ring expansion

Scheme 42

Synthesis of nezukone via dihalocarbene

Scheme 43

Synthesis of γ-thujaplicin via dihalocarbene

Scheme 44

Halotropones and halotropolones derived from cyclopropanation and ring expansion

Scheme 45

Banwell’s synthesis of stipitatic acid and puberulic acid

Scheme 46

Evans’ formal synthesis of (±)-colchicine

Scheme 47

Evans’ total synthesis of β-dolabrin

Scheme 48

Synthesis of stipitatic acid via cyclopropylquinone

Scheme 49

Banwell’s synthesis of MY3-469 and isopygmaein by sulfur ylide-mediated cyclopropanation

Scheme 50

Banwell’s synthesis of (−)-colchicine by sulfur ylide-mediated cyclopropanation

Scheme 51

Banwell’s synthesis of imerubrine and grandirubrine

Scheme 52

Feldman’s synthesis of pareitropone via ring expansion of alkylidene cyclopropane

Scheme 53

Ring expansion followed by oxidation of cycloheptanone to tropone

Scheme 54

Synthesis of goupiolone A via ring expansion of cyclopropyl-benzocyclobutenes and structural revision

Scheme 55

Transformation of perezone to pipitzol

Scheme 56

Synthesis of substituted tropolones via perezone type [5+2] cycloaddition

Scheme 57

Biomimetic synthesis of (±)-deoxyepolone B

Scheme 58

Synthetic effort towards cordytropolone

Scheme 59

Synthesis of tropolone subunit in a model compound for rubroloneaglycon via cycloaddition of oxidopyrylium ion

Scheme 60

Total synthesis of (±)-harringtonolide

Scheme 61

Synthesis of tropone from [5+2] cycloaddition product in a model system for (±)-harringtonolide

Scheme 62

Synthesis of hydroxytropolones

Scheme 63

Synthesis of stipitatic acid and β-thujaplicin via 1,3-dipolar cycloaddition

Scheme 64

Synthesis of benzotropolones through Rh (II) catalyzed [3+2] cycloaddition

Scheme 65

Biomimetic synthesis of (±)-epolone B analogue

Scheme 66

Schmalz’s synthesis of (−)-colchicines via Rh-catalyzed carbonyl ylide cycloaddition

Scheme 67

Noyori’s synthesis of β-thujaplicin via oxyallylcation [4+3] cyclization

Scheme 68

Preparation of 3-methyl tropone via oxyallylcation [4+3] cycloaddition

Scheme 69

Cha’s synthesis of (−)-colchicine via oxyallylcation [4+3] cycloaddition

Scheme 70

Synthesis of imerubrine via oxyallylcation [4+3] cycloaddition

Scheme 71

Davies’s synthesis of nezukone

Scheme 72

Wenkert’s synthesis of nezukone via cyclopropanation and Cope rearrangement

Scheme 73

Wenkert’s formal synthesis of (±)-colchicine via cyclopropanation and Cope rearrangement

Scheme 74

Boger’s formal synthesis of (±)-colchicines via cycloaddition of cyclopropenone ketal with α-pyrone

Scheme 75

Synthesis of tropolone via [2+2] cycloaddition of cyclopentadiene with dihaloketene and its application in a formal synthesis of colchicine

Scheme 76

Synthesis of 3-substituted tropone (e.g. nezukone) under photolytic conditions

Scheme 77

Synthesis of rubroloneaglycon via [2+2] cycloaddition and fragmentation

Scheme 78

Synthesis of grandirubrine and imerubrine via cycloaddition of cyclopropenone ketal and α-pyrone

Scheme 79

Synthesis of rubroloneaglycon via cycloaddition of cyclopropenone ketal and ring expansion

Scheme 80

Synthesis of tropolones from cycloaddition of furan with TBCP and its application to the synthesis of thujaplicin

Scheme 81

Synthesis of tropones via [4+2] cycloaddition followed by rearrangement