A convenient procedure for hydrozirconation of alkynes with iso-BuZrCp2Cl generated in situ by treatment of Cp2ZrCl2 with tert-butylmagnesium chloride

Swanson, Douglas R.; Thinh, Nguyen Van Thinh Nguyen Van; Noda, Y.; Negishi, Ei‐ichi

doi:10.1021/jo00007a062

Cited by 54 publications

(24 citation statements)

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“…Hydrozirconation of the silyl-protected alcohols 9 with Schwartz×s reagent [20] formed in situ and subsequent addition of iodine gave (E)-vinyl iodides 10 required for prostanoid synthesis (Scheme 5). Confirmation of the absolute configuration of vinyl iodide 10a and hence alcohol 6a, was obtained by transformation to travoprost.…”

Section: Resultsmentioning

confidence: 99%

An Enantioconvergent Synthesis of (R)-4-Aryloxy-1-butyne-3-ols for Prostanoid Side Chains

Fox¹,

Jackson²,

Lennon³

et al. 2002

Advanced Synthesis & Catalysis

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Section: Resultsmentioning

confidence: 99%

An Enantioconvergent Synthesis of (R)-4-Aryloxy-1-butyne-3-ols for Prostanoid Side Chains

Fox¹,

Jackson²,

Lennon³

et al. 2002

Advanced Synthesis & Catalysis

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“…Likewise, hydrozirconation of isobutylene is slow and generates the iso-butyl organometallic rather than the tert-butyl reagent. [17] Entries 1, 3-5 highlight ketones derived from branched Grignard reagents. Again, these products could not be accessed through hydrozirconation with Schwartz reagent because the linear isomers would dominate.…”

Section: Hhs Public Accessmentioning

confidence: 99%

“…Exclusive selectivity was observed for the SN2′ product using a propargyl bromide (22). The coupling reaction itself was generally clean, but careful purification was required to avoid isomerization to the conjugated enone with the unsubstituted allyl group (17) or elimination to form the allene with the vinyl bromide in entry 3. [25] To extend the carbonylative coupling to electrophiles beyond allyl and propargyl halides, we explored trapping the acyl zirconium species with iodonium salts.…”

Section: Introductionmentioning

confidence: 99%

“…However, the intermediate (alkyl)ZrClCp 2 underwent rapid loss of isobutylene to form Cp 2 Zr(H)Cl in situ. [16,17,18] In other relevant work, alkyl lithium and Grignard reagents are known to reduce Cp 2 ZrCl 2 to low valent zirconium complexes. [19] By contrast, we were interested in accessing alkyl zirconium species and trapping them with suitable electrophiles.…”

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confidence: 99%

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Zirconocene‐Mediated Carbonylative Coupling of Grignard Reagents

2016

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Organozirconocenes are versatile synthetic intermediates that can undergo carbonylation to yield acyl anion equivalents. Zirconocene hydrochloride (Cp 2 ZrHCl) is often the reagent of choice for accessing these intermediates but generates organozirconocenes only from alkenes and alkynes. This requirement eliminates a broad range of substrates including aromatic rings, benzylic groups, and alkyl groups that possess a tertiary or quaternary carbon alpha to the carbon-zirconium bond. To provide more generalized access to acyl zirconium reagents, we explored transmetalation of Grignard reagents with zirconocene dichloride under a CO atmosphere. This protocol generates acyl zirconium (IV) complexes that are inaccessible using the Schwartz reagent, including those derived from secondary and tertiary alkyl and aryl Grignard reagents. Graphical AbstractAcyl zirconocenes [Cp 2 ZrCl(COR)] are valuable acyl anion equivalents in synthetic chemistry. Traditionally, they have been prepared through hydrozirconation of olefins or alkynes, precluding generation of aryl, benzyl, tertiary alkyl or branched acyl zirconocenes. Here we describe a Zrmediated carbonylative coupling of Grignard reagents that involves previously inaccessible zirconocene intermediates.Correspondence to: Joseph M. Ready, joseph.ready@utsouthwestern.edu. Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate)) [2,3,4,5] Among the most useful transformations of organozirconocenes is their carbonylation to yield acyl zirconium complexes. [6] These reagents serve as acyl anion equivalents and can undergo oxidation to yield carboxylic acid derivatives and react in C-C bond forming processes to yield unsymmetrical ketones. For example, acyl zirconium reagents add to ketones and enones to form α-hydroxy ketones and 1,4-diketones, respectively. [7] Additionally, they couple with aryl and allyl electrophiles under metalmediated conditions. [8,9,10] Enantio-selective transformations of acyl zirconocenes have been developed to generate optically active ketone derivatives. [11] Organozirconium reagents are generally prepared by hydrozirconation of olefins or alkynes. These hydrometalations are highly regioselective, generally providing the less hindered alkyl or vinyl zirconium intermediate. [12] Indeed, hydrozirconation of internal olefins usually forms the terminal alkyl complex product through an isomerization sequence involving reversible hydrozirconation/β-hydride elimination (Scheme 1). [1] Additionally, hydrozirconation necessarily results in a zirconium complex with a β-C-H bond. This requirement excludes broad substrate classes including aryl and benzyl zirconium complexes. We sought to expand the scope of available organozirconium reagents through transmetalation from readily available organometallic species. While unprecedented, such a process could yield zirconium reagents that are currently inaccessible through hydrozirconation, including aryl-benzyl-and tertiary and sec...

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“…[233] Zirconocene dichloride is readily available, and less expensive than the Schwartz reagent, zirconocene hydridochloride. By zirconium-iodine and then iodine-lithium exchange, the trans-alkenyllithium is obtained, which is reacted first with lithium 2-thienylcyanocuprate and then with the tricycle.…”

Section: Travoprostmentioning

confidence: 99%

Pharmaceuticals

Schaefer

2014

Natural Products in the Chemical Industry

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A boy who is born in Germany today has a probable life expectancy of around 77 years, and a girl one of 82 years -twice as long as in the year 1880. This increase is a consequence of both, better living circumstances -working conditions, food, clothing, housing -, and also a result of more comprehensive medical care. Thus, a whole range of infectious diseases has been wiped out, or brought at least under control, and the mortality rate for civilisation-and age-related diseases has dropped. Vaccinations and drugs play a key role in this outcome. The 20th century is characterised especially by the worldwide blossoming of the pharmaceutical industry. More and more, the targeted search for and development of new drugs have replaced serendipitous discoveries (Fig. 5.1). Pharmaceuticals of the last century.

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A convenient procedure for hydrozirconation of alkynes with iso-BuZrCp2Cl generated in situ by treatment of Cp2ZrCl2 with tert-butylmagnesium chloride

Cited by 54 publications

References 0 publications

An Enantioconvergent Synthesis of (R)-4-Aryloxy-1-butyne-3-ols for Prostanoid Side Chains

An Enantioconvergent Synthesis of (R)-4-Aryloxy-1-butyne-3-ols for Prostanoid Side Chains

Zirconocene‐Mediated Carbonylative Coupling of Grignard Reagents

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