Regioselective Aryl Radical Cyclization. 1. Stereocontrolled Synthesis of Linearly Condensed Hydroaromatic Carbocyclic Systems through 6-endo-Ring Closures

Pal, Sitaram; Mukhopadhyaya, Jayanta K.; Ghatak, Usha Ranjan

doi:10.1021/jo00089a009

Cited by 29 publications

(15 citation statements)

References 1 publication

(5 reference statements)

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“…7 Reduction of the ketone was accomplished with sodium borohydride in methanol to give the alcohol 16 as a pair of epimers (83:17) in 80% yield. Catalytic hydrogenolysis 14 of 16 gave (+)-yatein (17) 15 In conclusion, we have increased the diastereoselectivity of our previously reported aldol reaction by using LiCl as additive. The obtained 2,3-disubstituted g-butyrolactones were successfully converted into a broad range of different lignans.…”

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confidence: 71%

A General Approach to the Asymmetric Synthesis of Lignans: (-)-Methyl Piperitol, (-)-Sesamin, (-)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (-)-Isostegane

Enders¹,

Lausberg²,

Signore³

et al. 2002

Synthesis

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A highly efficient, diastereo-and enantioselective route was developed to access a great variety of lignans. The asymmetric synthesis of the 2,3-disubstituted g-butyrolactones 9a-c could be improved in the case of aldol reactions by employing 2.2 equivalents of LiCl as an additive to provide, after purification, highly diastereo-and enantioenriched starting materials for the synthesis of the furofuran lignans (-)-methyl piperitol, (-)-sesamin, and (-)-aschantin. Furthermore, the g-butyrolactone 15 was converted into dibenzylbutyrolactone lignan (+)-yatein, the dibenzylbutandiol type (+)-dihydroclusin, the tetrahydrofuran type (+)-burseran, and the dibenzocyclooctadiene type (-)-isostegane.

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confidence: 71%

A General Approach to the Asymmetric Synthesis of Lignans: (-)-Methyl Piperitol, (-)-Sesamin, (-)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (-)-Isostegane

Enders¹,

Lausberg²,

Signore³

et al. 2002

Synthesis

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“…31 Compound 24 , however, was found to give a mixture of the 5‐ exo cyclization product 25 and the 6‐ endo cyclization product 26 in 39 and 52% yields, respectively 32,33. More interestingly, compound 27 gave only the 6‐ endo cyclization product 28 in 95% yield 34,35…”

Section: ‐Exo Vs 6‐endo Radical Cyclizationsmentioning

confidence: 98%

“…It has been reported that the exclusive formation of 28 from 27 was achieved under conditions using 0.007–0.02 M of 27 35. If the concentration of 27 or Bu 3 SnH was very high, the intermediate radical 29 might be trapped by Bu 3 SnH immediately to give a five‐membered compound 32 (Fig.…”

Section: ‐Exo Vs 6‐endo Radical Cyclizationsmentioning

confidence: 98%

Controlling the regiochemistry of radical cyclizations

Ishibashi

2006

The Chemical Record

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This review describes the results of our recent studies on the control of the regiochemistry of radical cyclizations. N-vinylic alpha-chloroacetamides generally cyclized in a 5-endo-trig manner to give five-membered lactams, whereas 4-exo-trig cyclization occurred when the cyclized radical intermediates were highly stabilized by an adjacent phenyl or phenylthio group to afford beta-lactams. The 5-exo or 6-exo cyclization of aryl radicals onto the alkenic bond of enamides could be shifted to the corresponding 6-endo or 7-endo mode of cyclization by a positional change of the carbonyl group of enamides. The 6-endo- and 7-endo-selective aryl radical cyclizations were applied to radical cascades for the synthesis of alkaloids such as phenanthroindolizidine, cephalotaxine skeleton, and lennoxamine. The 5-exo-trig cyclization of an alkyl radical onto the alkenyl bond of enamides could also be shifted to the 6-endo mode by a positional change of the carbonyl group of enamides. The 6-endo- selective cyclization was applied to the radical cascade to afford a cylindricine skeleton. Other examples of controlling the regiochemistry of radical cyclizations and their applications to the synthesis of natural products are also discussed.

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“…Thus, hydrolysis of 6 with lithium hydroxide in methanol-water and subsequent decarboxylation by heating a silica gel slurry of the resulting acid afforded the cyclohexenone 4b (Scheme 3). Syntheses of the other cyclohexenones 4c 6 and 4d 4a (Scheme 4) were reported earlier.…”

mentioning

confidence: 97%

“…The latter could in turn be prepared through alkylation of suitably substituted benzyl bromides with the methyl analogue of Hagemann's ester, easy decarboxylation to the cyclohexenones, and subsequent introduction of a methyl or carbomethoxy group at the b-position of the conjugated carbonyl system. Thus, the freshly prepared 2-bromobenzyl bromide 1 5 was reacted 6 (Scheme 2) with the methyl analogue (2) of Hagemann's ester in the presence of potassium tert-butoxide and sodium iodide to afford 3. The ester 3 was hydrolyzed and decarboxylated in one pot by refluxing with potassium hydroxide in aqueous ethanol to furnish the cyclohexenone 4a.…”

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confidence: 99%

An Improved Synthetic Route to Angularly Functionalized Hydrofluorene Derivatives through Pd(0)-Catalyzed Heck Reaction

Banerjee¹,

Mukhopadhyay²,

Achari³

et al. 2006

Synthesis

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4a-Substituted 1,1-dimethyl or 1-carbomethoxy-1-methyl hydrofluorenes carrying various substituents in the aromatic ring could be conveniently synthesized by Pd(0)-catalyzed Heck reaction. The required bromobenzyl-substituted ethylidene cyclohexane substrates were derived from Hagemann's ester (methyl analogue) via condensation with appropriate benzyl bromide, hydrolytic decarboxylation of the ester, 1,4-addition of methyl or cyano group followed by necessary functional group manipulation, and Wittig olefination. Simple organic transformations converted the vinyl group to carboxy, formyl or hydroxymethyl. The ring juncture stereochemistry of the products could be ascertained by correlation approach.Hydrofluorenes constitute the basic skeleton of a large number of highly functionalized diterpenoids of the gibberellin and rearranged abietane groups, but synthetic methodologies for these important and apparently simple molecules have been scant. Though there are few reports on the syntheses of 4a-substituted hydrofluorenes, 1,2 only a single methodology established by Ghatak and coworkers 2 is available, to our knowledge, for the synthesis of 4a-(carboxyl)-substituted hydrofluorenes carrying substituents at C-1 position; the corresponding position in gibberellins usually carry a methyl and a carboxyl group. As these products are expected to serve as putative intermediates to C-10 functionalized gibberellins, we became interested to develop an improved synthetic methodology for 1,1-disubstituted hydrofluorenes with diverse functional groups at the 4a-position.Inserting a vinyl group at the angular position of hydrofluorenes appeared to us as particularly promising, as it can be easily transformed to other functional groups. Trost et al. first reported 3 the synthesis of hydrofluorenes with a 4a-vinyl substituent by palladium-catalyzed reductive cyclization. Although the yields achieved were moderate to good, the methodology involves a complex reagent system and only C-1 unsubstituted hydrofluorenes were synthesized. We have recently reported the results of our fruitful venture in harnessing the Pd(0)-catalyzed Heck reaction for the synthesis of several complex diterpenoids. 4 In continuation of that exercise we now describe a simple, generalized and high-yielding method using Pd(0)-catalyzed intramolecular cyclization to produce a series of functionalized hydrofluorenes with substituents at C-1, C-4a and the aromatic ring. Easy transformations of the vinyl group to many other functionalities are also demonstrated.The retrosynthetic plan is described in Scheme 1. The required 2-(2-bromobenzyl)-1-ethylidenecyclohexane intermediates were obtainable from the respective cyclohexanones. The latter could in turn be prepared through alkylation of suitably substituted benzyl bromides with the methyl analogue of Hagemann's ester, easy decarboxylation to the cyclohexenones, and subsequent introduction of a methyl or carbomethoxy group at the b-position of the conjugated carbonyl system. Scheme 1 Retrosynthetic plan R 3 R 2 M e...

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Regioselective Aryl Radical Cyclization. 1. Stereocontrolled Synthesis of Linearly Condensed Hydroaromatic Carbocyclic Systems through 6-endo-Ring Closures

Cited by 29 publications

References 1 publication

A General Approach to the Asymmetric Synthesis of Lignans: (-)-Methyl Piperitol, (-)-Sesamin, (-)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (-)-Isostegane

A General Approach to the Asymmetric Synthesis of Lignans: (-)-Methyl Piperitol, (-)-Sesamin, (-)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (-)-Isostegane

Controlling the regiochemistry of radical cyclizations

An Improved Synthetic Route to Angularly Functionalized Hydrofluorene Derivatives through Pd(0)-Catalyzed Heck Reaction

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