Enantioselective Synthesis of 1,2,3-Trisubstituted Cyclopropanes Using <i>gem</i>-Dizinc Reagents

Zimmer, Lucie E.; Charette, André B.

doi:10.1021/ja906033g

Cited by 65 publications

(26 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Synthesis of these materials began with allyl alcohol 8 (Scheme 1), a central component prepared on the multigram scale for the synthesis of 1a . 6 Using a Charette cyclopropanation, 27 we were able to obtain cyclopropanol 9 as a single diasteromer. Oxidation with Dess-Martin periodinane afforded aldehyde 10 in 66% yield from 8 .…”

Section: Resultsmentioning

confidence: 99%

Stabilized Cyclopropane Analogs of the Splicing Inhibitor FD-895

Villa

Kashyap²,

Kumar³

et al. 2013

J. Med. Chem.

View full text Add to dashboard Cite

Targeting the spliceosome with small molecule inhibitors provides a new avenue to target cancer by intercepting alternate splicing pathways. Although our understanding of alternate mRNA splicing remains poorly understood, it provides an escape pathway for many cancers resistant to current therapeutics. These findings have encouraged recent academic and industrial efforts to develop natural product spliceosome inhibitors, including FD-895 (1a), pladienolide B (1b) and pladienolide D (1c), into next-generation anticancer drugs. The present study describes the application of semi-synthesis and total synthesis to reveal key structure activity relationships (SARs) for the spliceosome inhibition by 1a. This information is applied to deliver new analogs with improved stability and potent activity at inhibiting splicing in patient derived cell lines.

show abstract

Section: Resultsmentioning

confidence: 99%

Stabilized Cyclopropane Analogs of the Splicing Inhibitor FD-895

Villa

Kashyap²,

Kumar³

et al. 2013

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…Different approaches have been reported to provide boryl‐substituted cyclopropanes in a diastereoselective manner, with only a few strategies being known for the preparation of optically active cyclopropylboronates. Scheme shows the methodologies developed toward the asymmetric synthesis of borylcyclopropanes: (a) cyclopropanation of chiral alkenylboronates, (b) reaction of allylic carbonates or phosphonates with diboron derivatives, (c) hydroboration of cyclopropenes, and (d) zinco‐cyclopropanation of allylic alcohols . These protocols are restricted to products having a methylene group in the cyclopropane skeleton, with the exception of the methodology that requires an allylic alcohol as the directing group and a chiral stoichiometric boron reagent (Scheme d) …”

Section: Methodsmentioning

confidence: 99%

Enantio‐ and Diastereoselective Cyclopropanation of 1‐Alkenylboronates: Synthesis of 1‐Boryl‐2,3‐Disubstituted Cyclopropanes

2018

View full text Add to dashboard Cite

A novel, highly enantio- and diastereoselective synthesis of 1-boryl-2,3-disubstituted cyclopropanes has been developed by means of the cyclopropanation of alkenylboronates with ethyl diazoacetate in the presence of catalytic amounts of a chiral copper(I) complex. The products can also be directly accessed from alkynes through an operationally simple, sequential hydroboration-cyclopropanation protocol. The resulting enantioenriched 1-boryl-2,3-disubstituted cyclopropanes are versatile synthetic intermediates that undergo further transformations at the carbon-boron bond.

show abstract

“…The synthesis of enantioenriched cyclopropane containing scaffolds constitutes an ongoing challenge in organic synthesis despite significant advancements over the past few decades. 1 – 4 The dominant strategies 5 – 7 construct stereoselectively cyclopropanes from olefins and the metal-catalyzed decomposition of diazoesters, 8 – 11 the addition of zinc carbenoid 12 , 13 or the Michael addition followed by an 1,3-elimination reaction. 14 – 21 An alternative approach consists in the manipulation of an existing scaffold and in this context the carbometalation of cyclopropenes has proven to be a very efficient method leading to a large variety of polysubstituted cyclopropane derivatives from a single precursor.…”

Section: Introductionmentioning

confidence: 99%