Enantioselective Catalysis of Ketoester-ene Reaction of Silyl Enol Ether to Construct Quaternary Carbons by Chiral Dicationic Palladium(II) Complexes

Mikami, Kōichi; Kawakami, Yuji; Akiyama, Katsuhiro; Aikawa, Kohsuke

doi:10.1021/ja076539f

Cited by 93 publications

(23 citation statements)

References 22 publications

(19 reference statements)

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“…The convergent coupling reaction that unites building blocks 4 and 5 to begin the construction of the right-half intermediate is based on a palladium-catalysed ene reaction developed by Mikami and co-workers, and proceeds in 93% yield and 92% enantiomeric excess (e.e.) 37 . Two convergent coupling reactions follow three linear functional group interconversions, the first coupling being a Mukaiyama 38 aldol reaction (to incorporate building block 6 39 ) whose diastereoselectivity was observed to be dependent upon the reaction conditions.…”

Section: Synthesis Of 14-membered Azaketolidesmentioning

confidence: 99%

A platform for the discovery of new macrolide antibiotics

Seiple

Zhang

Jakubec

et al. 2016

Nature

283

214

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The chemical modification of structurally complex fermentation products, a process known as semisynthesis, has been an important tool in the discovery and manufacture of antibiotics for the treatment of various infectious diseases. However, many of the therapeutics obtained in this way are no longer effective, because bacterial resistance to these compounds has developed. Here we present a practical, fully synthetic route to macrolide antibiotics by the convergent assembly of simple chemical building blocks, enabling the synthesis of diverse structures not accessible by traditional semisynthetic approaches. More than 300 new macrolide antibiotic candidates, as well as the clinical candidate solithromycin, have been synthesized using our convergent approach. Evaluation of these compounds against a panel of pathogenic bacteria revealed that the majority of these structures had antibiotic activity, some efficacious against strains resistant to macrolides in current use. The chemistry we describe here provides a platform for the discovery of new macrolide antibiotics and may also serve as the basis for their manufacture.

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Section: Synthesis Of 14-membered Azaketolidesmentioning

confidence: 99%

A platform for the discovery of new macrolide antibiotics

Seiple

Zhang

Jakubec

et al. 2016

Nature

283

214

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“…These results clearly show that the alkynyl moiety of ester 2a is essential for the formation of 3a . It is well known that concerted pericyclic ene-type reaction of silyl enol ethers with electrophiles, such as aldehydes or ketones, gives functionalized silyl enol ethers without desilylation [22–36]. To the best of our knowledge, however, this is the first example of the introduction of simple alkyl groups through a substitution-type reaction [37–40].…”

Section: Resultsmentioning

confidence: 99%

Gold-catalyzed alkylation of silyl enol ethers with ortho-alkynylbenzoic acid esters

Aikawa¹,

Kaneko²,

Asao³

et al. 2011

Beilstein J. Org. Chem.

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SummaryUnprecedented alkylation of silyl enol ethers has been developed by the use of ortho-alkynylbenzoic acid alkyl esters as alkylating agents in the presence of a gold catalyst. The reaction probably proceeds through the gold-induced in situ construction of leaving groups and subsequent nucleophilic attack on the silyl enol ethers. The generated leaving compound abstracts a proton to regenerate the silyl enol ether structure.

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“…Trifluoroacetyl ketone analogues have recently received considerable attention (Scheme , R 2 =CF 3 ),4, 8a–c but there are only two reports in which an alkyl substituent has been installed at the α‐position 5. Because of very long reaction times, which are required with pyruvates,5a or the need to use a highly activated enolsilyl counterpart to decrease reaction times,5b the impression given by these reports is that effective asymmetric carbonyl–ene reactions are restricted to glyoxylates,1 and that the development of a general, asymmetric process which extends the complexity and functionality of the product is a challenging task.…”

Section: Methodsmentioning

confidence: 99%