Synthesis of α-Necrodol:  Unexpected Formation of a Cyclopropene

Taber, Douglass F.; Yu, Han

doi:10.1021/jo961780q

Cited by 24 publications

(14 citation statements)

References 15 publications

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“…Wills also reported 1,3-diastereomeric induction in the synthesis of dihydrofurans 235 and 236 from ketone 234 (Scheme 94 Proposing similar transition states 237e240 to Taber,7,123 Wills argued that the formation of 235 was more favourable due to the diminished steric interactions present in 237 by having both the CH 2 OTBS and phenyl groups in pseudoequatorial positions (Fig. 8).…”

Section: Diastereoselectivitymentioning

confidence: 94%

“…7 Taber also reported 1,3 diastereomeric induction in the reaction of ketone 226 to form cyclopentenes 227 and 228 in a 2.4:1 ratio (Scheme 93). 123 The benzyl group was removed to give the natural product a-necrodol, and its cis diastereoisomer. 123 Taber proposed four possible transition states 230e233 for the 1,5 CeH insertion reaction (Fig.…”

Section: Diastereoselectivitymentioning

confidence: 99%

“…123 The benzyl group was removed to give the natural product a-necrodol, and its cis diastereoisomer. 123 Taber proposed four possible transition states 230e233 for the 1,5 CeH insertion reaction (Fig. 7).…”

Section: Diastereoselectivitymentioning

confidence: 99%

“…This is believed to be due to the increased gauche interactions in 232 between the gem-dimethyl group and both pseudoequatorial substituents. 123 Interestingly, the major product in the reaction above was cyclopropene 229, the result of 1,3 CeH insertion (Scheme 93).…”

Section: Diastereoselectivitymentioning

confidence: 99%

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Recent advances in alkylidene carbene chemistry

Grainger

Munro

2015

Tetrahedron

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Section: Diastereoselectivitymentioning

confidence: 94%

Section: Diastereoselectivitymentioning

confidence: 99%

Section: Diastereoselectivitymentioning

confidence: 99%

Section: Diastereoselectivitymentioning

confidence: 99%

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Recent advances in alkylidene carbene chemistry

Grainger

Munro

2015

Tetrahedron

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“…of MCPBA, CH 2 Cl 2 , 408; 60%) afforded epoxy acid (+)-11c, alternatively also obtained in 39% yield by AgNO 3 /NaOH oxidation of (+)-11a. 14 ) For the synthesis of (À)-a-necrodol and epimers, see [16a], then [21]. 15 ) (+)-(R,E)-18b: a 20 D = + 13.6.…”

mentioning

confidence: 99%

Analogues ofα-Campholenal (= (1R)-2,2,3-Trimethylcyclopent-3-ene-1-acetaldehyde) as Building Blocks for (+)-β-Necrodol (= (1S,3S)-2,2,3-Trimethyl-4-methylenecyclopentanemethanol) and Sandalwood-like Alcohols

Chapuis

Barthe

Cantatore

et al. 2006

HCA

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To complete our panorama in structure-activity relationships (SARs) of sandalwood-like alcohols derived from analogues of a-campholenal (= (1R)-2,2,3-trimethylcyclopent-3-ene-1-acetaldehyde), we isomerized the epoxy-isopropyl-apopinene (À)-2d to the corresponding unreported a-campholenal analogue (+)-4d (Scheme 1). Derived from the known 3-demethyl-a-campholenal (+)-4a, we prepared the saturated analogue (+)-5a by hydrogenation, while the heterocyclic aldehyde (+)-5b was obtained via a Bayer-Villiger reaction from the known methyl ketone (+)-6. Oxidative hydroboration of the known acampholenal acetal (À)-8b allowed, after subsequent oxidation of alcohol (+)-9b to ketone (+)-10, and appropriate alkyl Grignard reaction, access to the 3,4-disubstituted analogues (+)-4f,g following dehydration and deprotection. (Scheme 2). Epoxidation of either (+)-4b or its methyl ketone (+)-4h, afforded stereoselectively the trans-epoxy derivatives 11a,b, while the minor cis-stereoisomer (+)-12a was isolated by chromatography (trans/cis of the epoxy moiety relative to the C 2 or C 3 side chain). Alternatively, the corresponding trans-epoxy alcohol or acetate 13a,b was obtained either by reduction/esterification from trans-epoxy aldehyde (+)-11a or by stereoselective epoxidation of the a-campholenol (+)-15a or of its acetate (À)-15b, respectively. Their cis-analogues were prepared starting from (+)-12a. Either (+)-4h or (À)-11b, was submitted to a Bayer-Villiger oxidation to afford acetate (À)-16a. Since isomerizations of (À)-16 lead preferentially to b-campholene isomers, we followed a known procedure for the isomerization of (À)-epoxyverbenone (À)-2e to the norcampholenal analogue (+)-19a. Reduction and subsequent protection afforded the silyl ether (À)-19c, which was stereoselectively hydroborated under oxidative condition to afford the secondary alcohol (+)-20c. Further oxidation and epimerization furnished the trans-ketone (À)-17a, a known intermediate of either (+)-b-necrodol (= (+)-(1S,3S)-2,2,3-trimethyl-4methylenecyclopentanemethanol; 17c) or (+)-(Z)-lancifolol (= (1S,3R,4Z)-2,2,3-trimethyl-4-(4-methylpent-3-enylidene)cyclopentanemethanol). Finally, hydrogenation of (+)-4b gave the saturated cis-aldehyde (+)-21, readily reduced to its corresponding alcohol (+)-22a. Similarly, hydrogenation of b-campholenol (= 2,3,3-trimethylcyclopent-1-ene-1-ethanol) gave access via the cis-alcohol rac-23a, to the cis-aldehyde rac-24.

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1,5‐X Insertions of Free Alkylidene Carbenes: A Theoretical Study

Zhou,

2023

Asian J Org Chem

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1,5‐X insertions of alkylidene carbenes are powerful methods to construct five‐membered carbocycles and heterocycles, but the mechanism of 1,5‐X insertions of alkylidene carbene remains controversial (concerted or stepwise?). Here we report the different mechanisms of 1,5‐X insertions of free alkylidene carbene based on DFT calculations. Except for the 1,5 S‐H insertions, all 1,5‐X insertions proceed through stepwise process via forming ylide intermediates. However, subsequent 1,2 rearrangements of ylides occur through different mechanisms. The formal 1,5 O‐H/N‐H insertions except S‐H insertions happen through deprotonation rather than insertion reactions, while other pathways including nucleophilic substitution, 2,3‐sigmatropic rearrangement and homolysis of O‐C bond are invoked in various 1,5 O‐C insertions. The competition between 1,5‐X insertions and other side reactions (1,2 migration, dealkylation) has been discussed to answer why sometimes target insertion products were not obtained.

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Synthesis of α-Necrodol: Unexpected Formation of a Cyclopropene

Cited by 24 publications

References 15 publications

Recent advances in alkylidene carbene chemistry

Recent advances in alkylidene carbene chemistry

Analogues ofα-Campholenal (= (1R)-2,2,3-Trimethylcyclopent-3-ene-1-acetaldehyde) as Building Blocks for (+)-β-Necrodol (= (1S,3S)-2,2,3-Trimethyl-4-methylenecyclopentanemethanol) and Sandalwood-like Alcohols

1,5‐X Insertions of Free Alkylidene Carbenes: A Theoretical Study

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