The Kulinkovich hydroxycyclopropanation reaction in natural product synthesis

Haym, Isabell; Brimble, Margaret A.

doi:10.1039/c2ob26082d

Cited by 70 publications

(30 citation statements)

References 108 publications

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“…The use of cyclopropanols and homoenolates in natural product and pharmaceutical synthesis has previously been reviewed , . This section will highlight selected applications of homoenolate reactivity towards the synthesis of complex targets, as well as the recent use of electrophilic homoenolates in synthesis.…”

Section: Synthesis Of Pharmaceuticals and Natural Productsmentioning

confidence: 99%

Modern Developments in the Chemistry of Homoenolates

Mills

Rousseaux

2018

Eur J Org Chem

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Homoenolates are unique synthetic intermediates which display umpolung reactivity. Homoenolates and homoenolate equivalents like cyclopropanols have seen a recent surge in popularity due to their particular utility for accessing β‐functionalized carbonyl derivatives. This popularity has been enabled by the development of protocols for facile access to cyclopropanols and homoenolates from a variety of readily available starting materials. This microreview will highlight common strategies for generating cyclopropanols and metal homoenolates, as well as procedures for homoenolate functionalization, with a particular emphasis on protocols that have appeared after 2003. As an amphoteric molecule, two main reactivity modes have been established: the homoenolate reacts as a carbon nucleophile for β‐functionalization reactions and/or as a carbonyl electrophile, a strategy which has only emerged in the past few years. This microreview will highlight the use of homoenolates as convenient intermediates for accessing especially challenging motifs. The use of homoenolate chemistry in the context of natural product and pharmaceutical synthesis will also be presented.

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Section: Synthesis Of Pharmaceuticals and Natural Productsmentioning

confidence: 99%

Modern Developments in the Chemistry of Homoenolates

Mills

Rousseaux

2018

Eur J Org Chem

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“…[19] With 15 in hand, the next step was to convert it into 8 using the Kulinkovich reaction. We first explored the standard and modified Kulinkovich reaction conditions [20] such as EtMgBr, Ti(OiPr) 4 ,T HF or MeMgBr,E tMgBr,T i(OiPr) 4 ,T HF or Cp 2 ZrCl 2 ,EtMgBr, Ti(OiPr) 4 ,THF,but none of them gave 8 in synthetically useful yield. We also investigated the possibility of employing aDreiding-Schmidt reaction between the lactone 15 and methyl 2-(bromomethyl)acrylate to install the oxaspirolactone moiety with an exo methylene group.…”

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confidence: 99%

Total Syntheses of Bisdehydroneostemoninine and Bisdehydrostemoninine by Catalytic Carbonylative Spirolactonization

Yin

Dai

2018

Angew Chem Int Ed

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The first total syntheses of the stemona alkaloids bisdehydroneostemoninine and bisdehydrostemoninine in racemic forms have been achieved. The synthetic strategy features a novel palladium-catalyzed carbonylative spirolactonization of a hydroxycyclopropanol to rapidly construct the oxaspirolactone moiety. It also features a Lewis acid promoted tandem Friedel-Crafts cyclization and lactonization to form the 5-7-5 tricyclic core of the target stemona alkaloids.

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“…New ligand systems have also been utilized to promote the enantioselective synthesis of cyclopropanols (although with moderate ee’s). 9a Numerous natural products have been synthesized using this reaction (Figure 2b), 15 and the reaction has been developed for large/process scale use (> 1kg). 16 …”

Section: C-c Bond Forming Reactionsmentioning

confidence: 99%