Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry

Filippini, Marie-Hélène; Rodríguez, Jean

doi:10.1021/cr970029u

Cited by 184 publications

(80 citation statements)

References 431 publications

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“…Reagents and conditions: (a) LDA, THF, -78ºC then CNCO 2 It is interesting to note that the intramolecular Diels-Alder reaction of the 5-vinyl-1,3-cyclohexadiene moiety is strongly preferred to other alternative intramolecular cycloadditions that were also attempted, in spite of the highly strained transition state presumably involved. Thus, when compound 13 (and also the corresponding dimethyl(vinyl)silyl analogue, 13 with R 2 = OSiMe 2 CH=CH 2 ), readily prepared from hydroxycarvone 10 as described in the Experimental section, was heated in toluene under the same conditions described above for 7, only the Diels-Alder adduct 14 was formed, without any appreciable amounts of the adduct resulting from the alternative intramolecular cycloaddition of the 1,3,10-undecatriene moiety being observed [12].…”

Section: Methodsmentioning

confidence: 99%

“…With the tricyclic system 15 at hand, we investigated the opening of the cyclopropane ring in order to elaborate the bicyclo[3.2.1]octane framework. In the literature, dissolving metal reductions with metal-ammonia systems has been the most frequently used method for the cleavage of cyclopropyl ketones [2]. The electron transfer homogenous reagent samarium(II) iodide has been less often used for this purpose, although some examples of samarium(II)-mediated cyclopropane cleavage of rigid cyclopropyl ketones have been described [2,13].…”

Section: Methodsmentioning

confidence: 99%

“…In the literature, dissolving metal reductions with metal-ammonia systems has been the most frequently used method for the cleavage of cyclopropyl ketones [2]. The electron transfer homogenous reagent samarium(II) iodide has been less often used for this purpose, although some examples of samarium(II)-mediated cyclopropane cleavage of rigid cyclopropyl ketones have been described [2,13]. When applied to the opening of 15, a regioselective cleavage of the C 1 -C 2 bond of the cyclopropane ring took place to cleanly afford the bicyclo[3.2.1]octane ring system (Scheme 3).…”

Section: Methodsmentioning

confidence: 99%

“…The widespread occurrence of this common structural motif in so many biologically active natural products has stimulated the preparation of simple non-natural structures containing the carbo-bicyclic system with variable functional diversity, many of which have also shown relevant biological activity. A logical consequence of the interest in this type of compounds has been the development of a plethora of synthetic methods for making bicyclo[3.2.1]octanes [2], in many cases appropriately functionalised to be useful intermediates in the synthesis of the more complex natural products containing this bicyclic subunit. Some of the more efficient methodologies developed for the preparation of the bicyclo[3.2.1]octane system are based in the selective fragmentation of different types of functionalised tricyclo[3.2.1.0 2.7 ]octane derivatives, whose tricyclic cores have been constructed basically using two methods, an intramolecular cyclopropanation of a double bond [2,3], or a bicycloannulation of cyclic dienolates with various Michael acceptors [2,4].…”

Section: Introductionmentioning

confidence: 99%

“…A logical consequence of the interest in this type of compounds has been the development of a plethora of synthetic methods for making bicyclo[3.2.1]octanes [2], in many cases appropriately functionalised to be useful intermediates in the synthesis of the more complex natural products containing this bicyclic subunit. Some of the more efficient methodologies developed for the preparation of the bicyclo[3.2.1]octane system are based in the selective fragmentation of different types of functionalised tricyclo[3.2.1.0 2.7 ]octane derivatives, whose tricyclic cores have been constructed basically using two methods, an intramolecular cyclopropanation of a double bond [2,3], or a bicycloannulation of cyclic dienolates with various Michael acceptors [2,4]. In this report we describe the preparation of several enantiopure bicyclo[3.2.1]octane systems 3 using an alternative approach for the construction of the bicyclic skeleton, one based on an intramolecular Diels-Alder (IMDA) reaction of a 5-vinyl-1,3-cyclohexadiene 1 and the regioselective cleavage of the obtained tricyclo-[3.2.1.0 2.7 ]octan-3-one intermediate 2 (Scheme 1) [5].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Highly Functionalised Enantiopure Bicyclo[3.2.1]- octane Systems from Carvone

et al. 2004

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of Highly Functionalised Enantiopure Bicyclo[3.2.1]- octane Systems from Carvone

et al. 2004

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A Novel and Highly Stereoselective Intramolecular Formal [3+3] Cycloaddition Reaction of Vinylogous Amides Tethered withα,β-Unsaturated Aldehydes: A Formal Total Synthesis of (+)-Gephyrotoxin

et al. 2001

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We have been exploring reactions of b-diketo equivalents 1 with a,b-unsaturated iminium salts 2 for the construction of heterocycles such as 3 (Scheme 1). [1±3] These reactions involve a sequence consisting of a Knoevenagel condensation followed by a six p-electron electrocyclic ring-closure, [4] thereby constituting a stepwise formal [33] cycloaddition [5±7] in which two s bonds are formed, along with a new stereocenter Scheme 1.[33] Cycloaddition reactions of vinylogous amides and a,bunsaturated iminium salts. Reagents and conditions: a) EtOAc/toluene 1:2, 150 8C, 15 ± 30 h, 76 ± 80 %; TBS tert-butyldimethylsilyl. adjacent to the heteroatom. This cycloaddition protocol can be classified as a sequential anionic ± pericyclic strategy for which the significance in natural product synthesis has been elegantly summarized by Tietze and Beifuss. [8] Our recent work on the use of vinylogous amides in this formal cycloaddition [1] has allowed us to envision an intramolecular version of this reaction. Since the vinylogous amide 1, which contains a functionalized tether, provided the formal cycloadduct 3 in good yields, [1] it is conceivable that the vinylogous amides 4, which are tethered with an a,b-unsaturated iminium ion, may lead to piperidinyl heterocycles 5, attractive as intermediates in the syntheses of natural alkaloids (Scheme 1). We report herein the first stereoselective intramolecular formal [33] cycloaddition reaction by using vinylogous amides that are tethered with iminium ions, and its application in a formal total synthesis of ()-gephyrotoxin. [9±11] Based on our previous studies, the formation of the a,bunsaturated iminium salt prior to the addition of a b-diketo nucleophile is crucial to the regio-and chemoselectivity of the intermolecular formal cycloaddition reaction. [1, 2a] Conditions and protocols that generate a,b-unsaturated iminium salts in the presence of the b-diketo nucleophile lead to low yields of the desired products, and/or to synthetically less useful byproducts resulting from various competing reaction pathways. [7b±e] However, the enal precursor to a,b-unsaturated iminium ions in the intramolecular variant also contains a vinylogous amide. Thus, controlling the extent of iminium ion formation before competing reactions take place is a major challenge.To demonstrate the feasibility of an intramolecular formal [33] cycloaddition, the vinylogous amides 6 and 7 were prepared [12,13] and treated with piperidine (2.0 equiv) and Ac 2 O (2.0 equiv) in EtOAc/toluene (1:2; concentration of vinylogous amides: 0.03 ± 0.30 m) at 858C for 1 h (Scheme 2). These are the standard reaction conditions that have been consistently employed for the formation of iminium salts. [1,2] Subsequent heating at 150 8C in a sealed tube led to the isolation of the desired heterocycles 8 and 9 in yields of 80 and 68 %, respectively. Furthermore, the chiral vinylogous amide 10 [12] led to the desired tricycle 11 in 55 % yield as a single diastereomer under the same reaction conditions. The stereochemistry of...

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C−C versus C−O Anionic Domino Cycloalkylation of Stabilized Carbanions: Facile One-Pot Stereoselective Preparation of Functionalized Bridged Bicycloalkanones and Cyclic Enol Ethers

et al. 2001

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alpha,alpha'-Diactivated cyclic- or acyclic ketones undergo a chemoselective base promoted (K2CO3, DBU) one-pot C-C cycloalkylation, with 1,3- and 1,4-dihalides having a cis-like fixed configuration. This reaction gives highly functionalized bicyclo[3.2.1]octan-9-one and bicyclo[4.2.1]nonan-9-one derivatives, which are easily transformed to seven- and eight-membered rings through a high yield retro-Dieckmann cleavage. Starting from trans-1,4-dibromo-2-butenes, the transformation is governed by stereoelectronic factors and leads, through a chemo- and stereoselective C-O cycloalkylation, to synthetically valuable monocyclic or fused polycyclic functionalized enol ethers of high synthetic value. Semiempirical calculations showed a small difference in energy and the late character of the transition states leading to cis and trans isomers of the corresponding fused polycyclic enol ethers. These results, although minimizing the influence of a destabilizing 1,3-interaction on the outcome of the reaction, are qualitatively in agreement with the experimental results.

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Synthesis of Functionalized Bicyclo[3.2.1]octanes and Their Multiple Uses in Organic Chemistry

Cited by 184 publications

References 431 publications

Synthesis of Highly Functionalised Enantiopure Bicyclo[3.2.1]- octane Systems from Carvone

Synthesis of Highly Functionalised Enantiopure Bicyclo[3.2.1]- octane Systems from Carvone

A Novel and Highly Stereoselective Intramolecular Formal [3+3] Cycloaddition Reaction of Vinylogous Amides Tethered withα,β-Unsaturated Aldehydes: A Formal Total Synthesis of (+)-Gephyrotoxin

C−C versus C−O Anionic Domino Cycloalkylation of Stabilized Carbanions: Facile One-Pot Stereoselective Preparation of Functionalized Bridged Bicycloalkanones and Cyclic Enol Ethers

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