Formal Synthesis of (+)-Phorbol<sup>1</sup>

Lee, Kwang-Ho; Kun, Jin

doi:10.1021/ja010643u

Cited by 112 publications

(58 citation statements)

References 26 publications

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“…[19] A simple case is 1,3-dibromobutan-2-one (12), which is formed by bromination of 2-butanone. [20] The reaction of 12 with furan in TFE/NaTFE gave a disappointing result with regards to the yield and stereoselectivity of the [4+3] cycloadducts (14). These were formed in a ratio of ca.…”

Section: Resultsmentioning

confidence: 99%

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Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Föhlisch¹,

Franz²,

Kreiselmeier³

2005

Eur J Org Chem

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Reactions of five acyclic dihalogeno‐ and trihalogeno ketones, representing the α,α‐, α,α′‐, α,α,α‐ and α,α,α′‐di‐ and trihalogeno substitution pattern, with sodium 2,2,2‐trifluoroethoxide in 2,2,2‐trifluoroethanol (NaTFE/TFE) in the presence of furan were investigated with the aim of obtaining [4+3] cycloadducts of the corresponding oxyallyl intermediates. Preference of Favorskii rearrangement over cycloaddition was observed with dichloromethyl isobutyl ketone (1a) and 1,3‐dibromobutan‐2‐one (12) that formed mainly the trifluoroethyl esters of 3‐chloro‐2‐isopropylpropanoic acid (9a), and (Z)‐but‐2‐enoic acid (isocrotonic acid) (13), respectively. 9a was dehydrohalogenated to form trifluoroethyl 3‐isopropylacrylate (11a). [4+3] Cycloaddition was favored with the 1,1,3‐trihalogenobutan‐2‐ones 24 and 25, leading to 2,4‐dihalogenated 8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐ones (26, 27) as a mixture of endo‐exo‐stereoisomers. With trichloromethyl isobutyl ketone (30) the isomeric 2,4‐dichloro‐substituted oxabicycles (34) were formed in lithium perchlorate/diethyl ether/furan/triethylamine, while in NaTFE/TFE solvolytic displacement of one chloro substituent occurred, providing 2‐chloro‐4‐trifluoroethoxy‐4‐isopropyl‐8‐oxabicyclo[3.2.1]oct‐6‐en‐3‐one (36). By analogy, 27 reacted with sodium methoxide/methanol to form the methoxy‐substituted oxabicycles 39a and 39b. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

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Section: Resultsmentioning

confidence: 99%

“…sodium 2,2,2-trifluoroethoxide in trifluoroethanol (NaTFE/TFE). [11][12][13] Apart from 1,1,3-trichloroacetone, [12,14] to the best of our knowledge, the behavior of other acyclic trihalogeno ketones under conditions of trifluoroethanolysis has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Föhlisch¹,

Franz²,

Kreiselmeier³

2005

Eur J Org Chem

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“…Successful total syntheses of this class of molecules were reported by Wender's group 11 and Cha's group, 12 before our laboratory disclosed the total synthesis of 1 in 2015. 13 Most recently, Baran's group described the biosynthesis-inspired elegant total synthesis of phorbol.…”

Section: Introductionmentioning

confidence: 96%

Asymmetric Total Synthesis of Crotophorbolone: Construction of the 5/7/6-Fused Ring System via an α-Alkoxy Bridgehead Radical Reaction

Urabe¹,

Asaba²,

Inoue³

2016

Bulletin of the Chemical Society of Japan

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This account describes the development of a synthetic route to crotophorbolone (1). Compound 1 is classified as a derivative of the tigliane diterpenoids, and possesses a highly oxygenated 5/7/6-fused ABC-ring system. First, the six-membered C-ring fragment with five contiguous stereocenters was stereoselectively constructed from (R)-carvone. Nucleophilic addition of the three-carbon unit to the C-ring and stereoselective attachment of the five-membered A-ring through a π-allyl Stille coupling reaction provided the substrate for the key radical cyclization. Next, treatment of the O,Se-acetal with V-40 and (TMS) 3 SiH in refluxing toluene generated the α-alkoxy bridge- head radical, which participated in the endo-cyclization of the seven-membered B-ring with formation of the sterically congested bond in C9-stereospecific and C10-stereoselective manners. The C11-methyl group controlled the C10-stereochemical outcome via a long-range steric interaction, which was supported by the calculated transition state of the abbreviated α-alkoxy bridgehead radical structure. Finally, the functional groups on the 5/7/6-membered ring system were manipulated by Rh-catalyzed C2-olefin isomerization, C13-decarboxylative oxidation and C4-hydroxylation, completing the first total synthesis of 1 in 33 steps from (R)-carvone.

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“…However, the successful total synthesis of daphnanes has been limited to reports from Wender's group, 18,19) despite extensive synthetic efforts by other research groups. [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] We also have been inspired by the formidable structures of daphnanes to launch a synthetic study of 1 as the initial target. This review summarizes our effort to develop a key radicalmediated three-component reaction and its application to the convergent assembly of the tricyclic ABC-ring system of 1.…”

Section: Introductionmentioning

confidence: 99%

Radical-Mediated Three-Component Reaction: A Study toward the Total Synthesis of Resiniferatoxin

Urabe

2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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This review summarizes the efforts to develop a radical-mediated three-component reaction and its application to a convergent approach to synthesize the 5/7/6-tricyclic framework (ABC-rings) of the densely functionalized dephnane diterpene, resiniferatoxin. The α-alkoxy bridgehead radical species, which was designed as the radical donor of the three-component reaction, was generated from O,Se-and O,Te-acetals under two different conditions. The generated α-alkoxy bridgehead radical effectively underwent the threecomponent reaction with α,β-unsaturated ketones and allyltributyltin/aldehyde under each of the conditions, giving rise to a wide variety of multiply functionalized 2,3-trans disubstituted cyclopentenone moieties. One of the established reactions was utilized as the key assembling reaction of the ABC-tricyclic framework of resiniferatoxin. The reaction of the bridgehead radical of the highly functionalized 6-membered C-ring, the 5-membered A-ring, and an allyltributyltin derivative effectively produced the C4-branched AC-rings. The last B-ring was constructed from the coupling adduct in two steps through the 7-endo cyclization, delivering the tricyclic framework possessing the correct C8 and 9-stereocenters of resiniferatoxin. The present methods demonstrate the power of the three-component reaction using an α-alkoxy bridgehead radical in a convergent approach to the complex architectures of daphnane diterpenes.

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Formal Synthesis of (+)-Phorbol¹

Cited by 112 publications

References 26 publications

Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Asymmetric Total Synthesis of Crotophorbolone: Construction of the 5/7/6-Fused Ring System via an α-Alkoxy Bridgehead Radical Reaction

Radical-Mediated Three-Component Reaction: A Study toward the Total Synthesis of Resiniferatoxin

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Formal Synthesis of (+)-Phorbol1

Cited by 112 publications

References 26 publications

Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Base‐Induced Trifluoroethanolysis of Acyclic Di‐ and Trihalogeno Ketones: Favorskii Rearrangement and [4+3] Cycloaddition

Asymmetric Total Synthesis of Crotophorbolone: Construction of the 5/7/6-Fused Ring System via an α-Alkoxy Bridgehead Radical Reaction

Radical-Mediated Three-Component Reaction: A Study toward the Total Synthesis of Resiniferatoxin

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Formal Synthesis of (+)-Phorbol¹