Total Syntheses of Guanacastepenes N and O

Gampe, Christian M.; Carreira, Erick M.

doi:10.1002/anie.201007644

Cited by 57 publications

(31 citation statements)

References 40 publications

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“…1–3 Stoltz and Tambar have reported a mild direct aryne insertion into C-C bonds. 1 They obtained an unexpected C-C addition product (boxed; Scheme 1) in comparable yield with the expected product.…”

Section: Introductionmentioning

confidence: 99%

“…Carreira and Gampe have applied this reaction to the total synthesis of guanacastepenes, 3 and a comprehensive review of their applications of this ring expansion reaction has recently been documented. 4 Comandini and Brezinsky computationally explored the potential energy surface of a radical/π-bond addition mechanism of o -benzyne to cyclopentadiene.…”

Section: Introductionmentioning

confidence: 99%

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A Theoretical Study of Cyclohexyne Addition to Carbonyl–C_α Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

Sader

2012

J. Org. Chem.

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The mechanism of cyclohexyne insertion into a C(O)-Cα bond of cyclic ketones, explored experimentally by the Carreira group, has been investigated using density functional theory. B3LYP and M06-2X calculations were performed in both gas phase and THF (CPCM, UAKS radii). The reaction proceeds through a stepwise [2+2] cycloaddition of cyclohexyne to the enolate, followed by three disparate ring opening possibilities of the cyclobutene alkoxide to give the product: 1) thermally-allowed conrotatory electrocyclic ring opening, 2) thermally-forbidden disrotatory electrocyclic ring opening, or 3) non-pericyclic C-C bond cleavage. Our computational results for the model alkoxide and potassium alkoxide systems show that the thermally-allowed electrocyclic ring opening pathway is favored by less than 1 kcal/mol. In more complex systems containing a potassium alkoxide (e–f), the barrier of the allowed conrotatory ring opening is disfavored by 4–8 kcal/mol. This suggests that the thermodynamically more stable disrotatory product can be formed directly through a “forbidden” pathway. Analysis of geometrical parameters and atomic charges throughout the ring opening pathways provides evidence for a non-pericyclic C-C bond cleavage, rather than a thermally-forbidden disrotatory ring opening. A true forbidden disrotatory ring opening transition structure was computed for the cyclobutene alcohol; however, it was 19 kcal/mol higher in energy than the allowed conrotatory transition structure. An alternate mechanism in which the disrotatory product forms via isomerization of the conrotatory product was also explored for the alkoxide and potassium alkoxide systems.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Theoretical Study of Cyclohexyne Addition to Carbonyl–C_α Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

Sader

2012

J. Org. Chem.

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“…Both isomers were then reacted under standard conditions known to elicit ketone α -peroxidation ( t -BuOK, O 2 ). 31–37 Unfortunately, we were unable to isolate any of diperoxide 3 ; the major product isolated under these conditions was determined to be epoxide 18 . These findings led us to speculate that either anion 4 does not undergo an anionic 7- endo cyclization at a rate comparable to epoxide formation or that the α -peroxidation occurs at the undesired carbonyl first and then forms the epoxide.…”

Section: Resultsmentioning

confidence: 96%

Synthesis and study of the antimalarial cardamom peroxide

Lim

Fairhurst

et al. 2018

Tetrahedron

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A full account of our previously disclosed synthesis of the monoterpene dimer cardamom peroxide is reported. Inspired by hypotheses regarding the potential biosynthetic origins of this natural product, several unproductive routes are also reported. The chemical reactivity of this structurally unique metabolite in the presence of iron(II) sources is also reported as is its antimalarial activity against Plasmodium falciparum clinical isolates from several Cambodian provinces.

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“…By contrast, treatment of 21 with a cyclohexenyl phenyliodonium salt, a known cyclohexyne precursor, gives none of 29 , further illustrating the utility of the CsF-promoted method for generating strained dienophiles. 32 Products such as 29 and 30 should facilitate access to BTX analogues with alternative D-ring and/or homomorpholine configurations than those highlighted in Table 1 and may allow for preparation of the natural product itself.…”

Section: Resultsmentioning

confidence: 99%

Modular synthesis of the pentacyclic core of batrachotoxin and select batrachotoxin analogue designs

Devlin

Bois

2013

Chem. Sci.

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Pentacyclic analogues of the potent voltage-gated sodium ion channel agonist batrachotoxin can be accessed through an intermediate furan by exploiting Diels-Alder cycloaddition reactions with ring-strained dienophiles. The use of 3-bromofuran as a 1,2-dianion equivalent, the application of carbamate reductive N-alkylation for homomorpholine ring assembly, and the demonstration of CsF as an effective reagent for generating benzyne, cyclohexyne, and related dienophiles underscore this work.

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Total Syntheses of Guanacastepenes N and O

Abstract: The cycloinsertion of cyclohexyne into a pentalene has provided access to the carbon scaffold of the guanacastepenes in nine steps. A late‐stage diversifying oxidation of the core structure enabled the synthesis of guanacastepene N and the first total synthesis of guanacastepene O.

Cited by 57 publications

References 40 publications

A Theoretical Study of Cyclohexyne Addition to Carbonyl–C_α Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

A Theoretical Study of Cyclohexyne Addition to Carbonyl–C_α Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

Synthesis and study of the antimalarial cardamom peroxide

Modular synthesis of the pentacyclic core of batrachotoxin and select batrachotoxin analogue designs

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Total Syntheses of Guanacastepenes N and O

Abstract: The cycloinsertion of cyclohexyne into a pentalene has provided access to the carbon scaffold of the guanacastepenes in nine steps. A late‐stage diversifying oxidation of the core structure enabled the synthesis of guanacastepene N and the first total synthesis of guanacastepene O.

Cited by 57 publications

References 40 publications

A Theoretical Study of Cyclohexyne Addition to Carbonyl–Cα Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

A Theoretical Study of Cyclohexyne Addition to Carbonyl–Cα Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

Synthesis and study of the antimalarial cardamom peroxide

Modular synthesis of the pentacyclic core of batrachotoxin and select batrachotoxin analogue designs

Contact Info

Product

Resources

About

A Theoretical Study of Cyclohexyne Addition to Carbonyl–C_α Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes

A Theoretical Study of Cyclohexyne Addition to Carbonyl–C_α Bonds: Allowed and Forbidden Electrocyclic and Nonpericyclic Ring-Openings of Strained Cyclobutenes