Herstellung enantiomerenangereicherter sekundärer Alkyllithium‐ und Alkylkupferverbindungen – Synthese von (−)‐Lardolure und Siphonarienal

Morozova, Varvara; Skotnitzki, Juri; Moriya, Kohei; Karaghiosoff, Konstantin; Knöchel, Paul

doi:10.1002/ange.201800792

Cited by 14 publications

(3 citation statements)

References 60 publications

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“…Therefore, the treatment of commerciallya vailable 1,2amino-alcohols (1a-e)d erived from optically enricheda minoacids [8] with 2,5-dimethoxytetrahydrofuran in the presence of NaOAc/AcOHi n1 ,2-dichloroethane (DCE) and water (90 8C, 1-16 h) produced the pyrrol-1-yl-alcohol derivatives 2a-e in 71-92 %y ield. [9] An Appel reaction [10] (PPh 3 ,I 2 ,i midazole in dichloromethane (DCM)) allowed the conversion of the alcohols 2a-e to the corresponding primary iodides 3a-e in 71-91 % yield. Direct insertion of zinc powder (1.5 equiv, > 325 mesh) previously activated with 1,2-dibromoethane (DBE) and Me 3 SiCl (TMSCl)t ot he alkyl iodides 3a-e in presence of LiCl [11] proceeded smoothly in THF at 25 8C( 10-90 min) furnishing the desired alkylzinc halides (4a-e)i n7 1-93 %y ield.…”

Section: Resultsmentioning

confidence: 99%

Pyrrole‐Protected β‐Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino‐Derivatives

Leroux

Huang

Lemke

et al. 2020

Chemistry A European J

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Chiral β‐aminoalkylzinc halides were prepared starting from optically pure commercial β‐amino‐alcohols. These amino‐alcohols were converted to the corresponding N ‐pyrrolyl‐protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 °C, 10–90 min). Subsequent Negishi cross‐coupling or acylation reactions with acid chlorides produced amino‐derivatives with retention of chirality. Diastereoselective CBS‐reductions of some prepared N ‐pyrrolyl‐ketones provided 1,3‐subsituted N ‐pyrrolyl‐alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole‐ring into a formamide without loss of optical purity.

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Section: Resultsmentioning

confidence: 99%

Pyrrole‐Protected β‐Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino‐Derivatives

Leroux

Huang

Lemke

et al. 2020

Chemistry A European J

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“…We were able to further extend this method to the functionalization of optically enriched secondary alkyl iodides . For example, ( R )‐ 3 i and ( S )‐ 3 i were obtained in good yield and enantioselectivity (73 % yield, 88 % ee ; 70 % yield, 90 % ee , see Scheme ).…”

Section: Methodsmentioning

confidence: 98%

“…This method afforded γ‐methyl unsaturated enones and enoates from relatively unfunctionalized secondary alkyllithiums. Only a few functional groups are tolerated by this method . Nevertheless, advanced precursors for the preparation of natural products were prepared to underline the synthetic value of this approach.…”

Section: Methodsmentioning

confidence: 99%

Diastereo‐ and Enantioselective Cross‐Couplings of Secondary Alkylcopper Reagents with 3‐Halogeno‐Unsaturated Carbonyl Derivatives

Kremsmair

Skotnitzki

Knöchel

2020

Chemistry A European J

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Chiral secondary alkylcopper reagents were prepared from the corresponding alkyl iodides with retention of configuration by an I/Li‐exchange using tBuLi (−100 °C, 1 min) followed by a transmetalation with CuBr⋅P(OEt)3 (−100 °C, 20 s). These stereodefined secondary alkylcoppers underwent stereoretentive cross‐couplings with several 3‐iodo or 3‐bromo unsaturated carbonyl derivatives leading to the corresponding γ‐methylated Michael acceptors in good yields and with high diastereoselectivities (dr up to 96:4). The method was extended to enantiomerically enriched alkylcoppers, providing optically enriched advanced natural product intermediates with up to 90 % ee.

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Regio‐ und stereoselektive allylische Substitutionen chiraler sekundärer Alkylkupferverbindungen: Totalsynthese von (+)‐Lasiol, (+)‐13‐Norfaranal und (+)‐Faranal

2018

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Chirale sekundäre Alkylkupferverbindungen wurden aus chiralen sekundären Alkyliodiden durch einen I/Li‐Austausch, gefolgt von einer retentiven Transmetallierung mit CuBr⋅P(OEt)3, hergestellt. Durch Wechseln des Lösungsmittels zu THF wird die konfigurative Stabilität der Kupferverbindungen signifikant verbessert und macht diese für regioselektive allylische Substitutionen brauchbar. Diese optisch angereicherten Kupferreagentien gingen SN2‐Substitutionen mit Allylbromiden (bis zu >99 % SN2‐Regioselektivität) ein. Versetzen mit ZnCl2 und die Verwendung von chiralen Allylphosphaten ermöglicht es, die Regioselektivität hin zu SN2′‐Substitutionen zu verschieben (bis zu >99 % SN2′‐Regioselektivität), sowie die Durchführung von äußerst selektiven anti‐SN2′‐Substitutionen mit kompletter Kontrolle von zwei nebeneinanderliegenden Stereozentren. Diese Methode wurde in der Naturstoffsynthese von drei Ameisenpheromonen – (+)‐Lasiol, (+)‐13‐Norfaranal und (+)‐Faranal (dr bis zu 98:2, 99 % ee) – angewendet.

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Herstellung enantiomerenangereicherter sekundärer Alkyllithium‐ und Alkylkupferverbindungen – Synthese von (−)‐Lardolure und Siphonarienal

Cited by 14 publications

References 60 publications

Pyrrole‐Protected β‐Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino‐Derivatives

Pyrrole‐Protected β‐Aminoalkylzinc Reagents for the Enantioselective Synthesis of Amino‐Derivatives

Diastereo‐ and Enantioselective Cross‐Couplings of Secondary Alkylcopper Reagents with 3‐Halogeno‐Unsaturated Carbonyl Derivatives

Regio‐ und stereoselektive allylische Substitutionen chiraler sekundärer Alkylkupferverbindungen: Totalsynthese von (+)‐Lasiol, (+)‐13‐Norfaranal und (+)‐Faranal

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