Synthesis of α,α′‐Disubstituted Linear Ethers by an Intermolecular Nicholas Reaction – Application to the Synthesis of (+)‐cis/(–)‐trans‐Lauthisan and (+)‐cis/(+)‐trans‐Obtusan

Ortega, Nuria; Martı́n, Tomás; Martı́n, Victor S.

doi:10.1002/ejoc.200801063

Cited by 23 publications

(7 citation statements)

References 76 publications

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“…The synthesis of larger medium rings is even more difficult due to the loss of entropy associated with the cyclization and the appearance of transannular repulsions arising when the ring starts to be formed. Previous syntheses of (‐)‐obtusan have been reported in the literature …”

Section: Resultsmentioning

confidence: 99%

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

et al. 2016

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The synthesis of 7-, 8-and 9-membered cyclic ethers isolaurepan, lauthisan and obtusan was achieved through the cisstereoselective TMSOTf/Et 3 SiH promoted reductive cyclization of the corresponding saturated hydroxy ketones, available in three steps from commercial starting materials: oxirane opening with lithium acetylide, Rh-catalyzed conjugate addition of the terminal alkynes to the corresponding unsaturated ketones and triple bond hydrogenation.

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Section: Resultsmentioning

confidence: 99%

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

et al. 2016

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“…In this case, the Cu-catalyzed allylation of the terminal acetylene was a suitable alternative to organometallic reagents . Although this reaction is known as a general method for the introduction of allyl moiety and has been extensively applied in the synthesis of natural products, , and even in the synthesis of enediyne systems, a one-pot technique for the TMS-group removal/allylation has been reported only once for the KF/CuI-mediated allylation of TMS phenylacetylene in DMF at 80 °C . In our case, much milder conditions were employed: addition of CuI and then allyl bromide to a prestirred mixture of acetylenes 12 and 13 with K 2 CO 3 /MeOH in DMF at room temperature gave the desired enyne 14 in high yield (90%).…”

Section: Resultsmentioning

confidence: 99%

Ring-Closing Metathesis of Co₂(CO)₆–Alkyne Complexes for the Synthesis of 11-Membered Dienediynes: Overcoming Thermodynamic Barriers

et al. 2015

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The feasibility of ring-closing metathesis (RCM) as a synthetic entry to 10- and 11-membered dienediynes fused to a benzothiophene core was explored by experimental and theoretical investigations. An established sequence of iodocyclization of o-(buta-1,3-diynyl)thioanisoles followed by Sonogashira coupling to form diethynylbenzothiophenes was used to synthesize terminal benzothiophene-fused enediyne diolefins as substrates for RCM. Encountering an unexpected lack of reactivity of these substrates under standard RCM conditions, we applied DFT calculations to reveal that the underlying cause was a positive change in Gibbs free energy. The change in Gibbs free energy was also found to be positive for RCM of indole- and benzannulated terminal diolefins when affording smaller than 12-membered rings. We found that modification of the enediyne-diolefin substrate as the Co2(CO)6-alkyne complex allowed the target benzothiophene-fused 11-membered dienediyne to be obtained via RCM; the alkyne complexation strategy therefore provides one valid technique for overcoming challenges to macrocyclization of this kind.

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“…Fortunately,t he reaction could be stopped at the tetrahydrofurans ent-cis-5 and enttrans-5 by using montmorillonite K-10 as mild acidic conditions (vide infra). [14] These compounds were obtained in an approximately equimolar ratio and their subsequent acetylation of the secondary alcohols allowed us to reach the diacetates ent-cis-6 and ent-trans-6 that were easily separated. [15] Analysis of the specific rotation values revealed that the latter are enantiomers of the diacetates cis-6 and trans-6, respectively.A dditionally,c hiral HPLC analysis of the benzoates ent-cis-7 and ent-trans-7 confirms that the reaction proceeded with total transfer of the enantiomeric purity from epoxide 3 (Scheme 2).…”

Section: Methodsmentioning

confidence: 99%

Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules

et al. 2020

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Inverting the reactivity of the functional groups in ambiphilic molecules provides a new synthetic strategy to perform late‐stage enantiodivergence. Both enantiomers of the final compound can be obtained from a common chiral precursor. As a proof of concept, the synthesis of substituted five‐ and six‐membered oxacycles is described. The key step is the cyclization of an ambiphilic linear precursor bearing a propargylic alcohol and an epoxide linked through an alkyl chain. Through a slight modification of these linear precursors and employing different reaction conditions, these functional groups can inverse their chemical reactivity, producing one enantiomer or another of the final product. This enantiodivergent cyclization involves three stereogenic centers that can undergo fully controlled retention or inversion of their configuration depending on the cyclization pathway that is activated. The cyclization provides late‐stage enantiodivergence, enabling the synthesis of either enantiomers of the oxacycles from a common chiral substrate with total transfer of the enantiomeric purity.

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Synthesis of α,α′‐Disubstituted Linear Ethers by an Intermolecular Nicholas Reaction – Application to the Synthesis of (+)‐cis/(–)‐trans‐Lauthisan and (+)‐cis/(+)‐trans‐Obtusan

Cited by 23 publications

References 76 publications

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

Ring-Closing Metathesis of Co₂(CO)₆–Alkyne Complexes for the Synthesis of 11-Membered Dienediynes: Overcoming Thermodynamic Barriers

Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules

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Synthesis of α,α′‐Disubstituted Linear Ethers by an Intermolecular Nicholas Reaction – Application to the Synthesis of (+)‐cis/(–)‐trans‐Lauthisan and (+)‐cis/(+)‐trans‐Obtusan

Cited by 23 publications

References 76 publications

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

Synthesis of Medium‐Sized 2,ω‐cis‐Disubstituted Cyclic Ethers by Reductive Cyclization of Hydroxy Ketones

Ring-Closing Metathesis of Co2(CO)6–Alkyne Complexes for the Synthesis of 11-Membered Dienediynes: Overcoming Thermodynamic Barriers

Enantiodivergent Cyclization by Inversion of the Reactivity in Ambiphilic Molecules

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Ring-Closing Metathesis of Co₂(CO)₆–Alkyne Complexes for the Synthesis of 11-Membered Dienediynes: Overcoming Thermodynamic Barriers