Preparation and thermal rearrangement of <i>trans</i>-3-[1-methyl-2-(2-methyl-1-propenyl)cyclopropyl]-2-cyclohexen-1-one. A synthesis of (±)-[β-himachalene

Piers, Edward; Ruediger, E. H.

doi:10.1139/v83-220

Cited by 19 publications

(5 citation statements)

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“…)-confertin (27) and to the preparation of an intermediate containing the basic carbon skeleton found in the tigliane, daphnane, and ingenane families of diterpenoids (32). Furthermore, as mentioned previously, the accompanying paper (38) describes the details of a synthesis of the sesquiterpenoid (? )-P-himachaIene via a route in which this new method played a key role.…”

Section: Resultsmentioning

confidence: 99%

“…This general section is applicable to the accompanying paper (38) as well as to the present paper. I , I-Di/~rott1o-2.2-tlb11eil1yl-3-vit1yl~:\.c~lo~11~r~~1r11r~~ (40) To a cold (-78°C) stirrcd suspcnsion of rncthyltriphcnylphosponium bro~nidc (6.24 g. 17.6 mmol) in 80 mL of tlry THF undcr an atmosphcrc of nitrogcn was addcd ;I solution of 11-butyllitliiu~n in hcxanc (6.5 mL.…”

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confidence: 95%

“…[6]). W e report herein the results of some of our studies in this area.3 In the accompanying paper (38) we describe the application of this new annulation method to a total synthesis of the bicyclic sequiterpenoid (2)-P-himachalene.…”

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confidence: 99%

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Seven-membered ring annulation and spiro-annulation processes via preparation and thermal rearrangement of β-(2-vinylcyclopropyl) α,β-unsaturated ketones

Piers¹,

Morton²,

Nagakura³

et al. 1983

Can. J. Chem.

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Treatment of the β-iodo enones 4 and 26–28 with lithium (phenylthio)(2-vinylcyclopropyl)cuprate (21, mixture of epimers), followed by thermolysis (180 °C, 30–45 min) of the initially formed β-(2-vinylcyclopropyl) enones, provided excellent yields of the seven-membered ring annulation products 25 and 30–32, respectively. In similar fashion, the (E)-2-(iodomethylene)cycloalkanones 8 and 29 were transformed efficiently into the spiro-annulation products 34 and 35 respectively. When compound 36 was treated with bromoform – sodium hydroxide in the presence of a phase-transfer catalyst, the dibromocyclopropane 37 was produced. The latter substance served as the starting material for a sequence of reactions (hydrolysis with hydrochloric acid in methanol, 37 → 38; oxidation with pyridinium chlorochromate, 38 → 39; Wittig reaction with methylenetriphenylphosphorane, 39 → 40; reduction with zinc in acetic acid, 40 → 41) culminating in the stereoselective formation of cis-1-bromo-2,2-dimethyl-3-vinylcyclopropane (41). On the other hand, treatment of compound 37 with n-butyllithium (ether, −90 °C), followed by protonation of the presumed intermediate 43 and hydrolysis of the resultant product 44, provided the bromo alcohol 45 in 70% yield. The latter substance was converted into trans-1-bromo-2,2-dimethyl-3-vinylcyclopropane (47). When the cuprate reagents 42 and 48 (prepared from the bromocyclopropanes 41 and 47, respectively) were allowed to react with the iodo enones 4 and 26, the β-(2-vinylcyclopropyl) α,β-unsaturated ketones 49, 52, 54, and 56 were produced in high yields. The enone 49, upon thermolysis in refluxing n-hexane, underwent facile Cope rearrangement to produce the annulation product 50 quantitatively. In contrast, the homolog 54 was notably resistant to [3,3]-sigmatropic rearrangement and, upon thermolysis in o-xylene, o-dichlorobenzene, or collidine at elevated temperatures produced, in varying ratios, the Cope rearrangement product 55 and the isomerization product 56. Thermal rearrangement (o-dichlorobenzene, 220 °C, sealed tube) of trans-3-(2,2-dimethyl-3-vinylcyclopropyl)-2-cyclohexen-1-one (52) provided the annulation product 51 (59% yield). In contrast, the corresponding homolog 56, under very similar conditions, produced only a minor amount of the annulation product 55. In this case, the major product (trienone 57) was that resulting from a [1,5]-sigmatropic hydrogen migration (ratio of 55/57 ≈ 1:4).

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Section: Resultsmentioning

confidence: 99%

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confidence: 95%

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Seven-membered ring annulation and spiro-annulation processes via preparation and thermal rearrangement of β-(2-vinylcyclopropyl) α,β-unsaturated ketones

Piers¹,

Morton²,

Nagakura³

et al. 1983

Can. J. Chem.

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“…In a similar way, a study of Dev and Shastri 40 showed that α-and β-himachalene can be obtained by Wagner-Meerwein rearrangement of longipinene with a variety of acids (BF 3 Piers and Ruediger 41 have described a total synthesis of β-himachalene 10 using cuprate 67 prepared from 5,5-dimethyl-2-vinyl-1,3-dioxane 61. The latter reacted with bromoform and sodium hydroxide in presence of a phase-transfer catalyst to give dibromocyclopropane 62.…”

Section: Introductionmentioning

confidence: 90%

The chemistry of the himachalenes and atlantones from Cedrus

Oukhrib¹,

Zaki²,

Benharref³

2018

Arkivoc

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Synthesis and functionalization of natural products are useful procedures to access and develop new and interesting molecules with biological properties. In this review we discuss the major sesquiterpenes isolated from the essential oil of cedar, which represents a family of abundant and inexpensive natural materials. Some total synthesis and chemical transformations described in the literature have been included.

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“…We next considered variants that contain one of the vinyl substituents in a cyclic geometry that would, upon contra-thermodynamic trans -to- cis isomerization followed by Cope-type rearrangement, result in a fused bicyclic product. Such processes, but thermally induced (more than 130 °C), have been used strategically in synthesis, including of natural products (for example, (+/−)- beta -himachalene 43 or karahanaenone 44 ). We observed that, under metalloradical catalysis, the analogous process happened cleanly at 60 °C starting from the trans -1-(2-vinylcyclopropyl)cyclohex-1-ene and delivered fused bicycle 46 in 97% yield (Fig.…”

Section: Mainmentioning

confidence: 99%

Dynamic stereomutation of vinylcyclopropanes with metalloradicals

Mendel,

Karl,

Hamm

et al. 2024

Nature

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The ever increasing demands for greater sustainability and lower energy usage in chemical processes call for fundamentally new approaches and reactivity principles. In this context, the pronounced prevalence of odd-oxidation states in less precious metals bears untapped potential for fundamentally distinct reactivity modes via metalloradical catalysis1–3. Contrary to the well-established reactivity paradigm that organic free radicals, upon addition to a vinylcyclopropane, lead to rapid ring opening under strain release—a transformation that serves widely as a mechanistic probe (radical clock)4 for the intermediacy of radicals5—we herein show that a metal-based radical, that is, a Ni(I) metalloradical, triggers reversible cis/trans isomerization instead of opening. The isomerization proceeds under chiral inversion and, depending on the substitution pattern, occurs at room temperature in less than 5 min, requiring solely the addition of the non-precious catalyst. Our combined computational and experimental mechanistic studies support metalloradical catalysis as origin of this profound reactivity, rationalize the observed stereoinversion and reveal key reactivity features of the process, including its reversibility. These insights enabled the iterative thermodynamic enrichment of enantiopure cis/trans mixtures towards a single diastereomer through multiple Ni(I) catalysis rounds and also extensions to divinylcyclopropanes, which constitute strategic motifs in natural product- and total syntheses6. While the trans-isomer usually requires heating at approximately 200 °C to trigger thermal isomerization under racemization to cis-divinylcyclopropane, which then undergoes facile Cope-type rearrangement, the analogous contra-thermodynamic process is herein shown to proceed under Ni(I) metalloradical catalysis under mild conditions without any loss of stereochemical integrity, enabling a mild and stereochemically pure access to seven-membered rings, fused ring systems and spirocycles.

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Preparation and thermal rearrangement of trans-3-[1-methyl-2-(2-methyl-1-propenyl)cyclopropyl]-2-cyclohexen-1-one. A synthesis of (±)-[β-himachalene

Cited by 19 publications

References 8 publications

Seven-membered ring annulation and spiro-annulation processes via preparation and thermal rearrangement of β-(2-vinylcyclopropyl) α,β-unsaturated ketones

Seven-membered ring annulation and spiro-annulation processes via preparation and thermal rearrangement of β-(2-vinylcyclopropyl) α,β-unsaturated ketones

The chemistry of the himachalenes and atlantones from Cedrus

Dynamic stereomutation of vinylcyclopropanes with metalloradicals

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