Zirconium-Catalyzed Carboalumination Research Articles

Zirconium-Catalyzed Carboalumination–Transmetalation

Zirconium-Catalyzed Carboalumination–Transmetalation

Strategies for the Synthesis of Deoxypropionates

Deoxypropionates constitute an important class of polyketide natural products. The biological properties of deoxypropionates are diverse and synthetic strategies toward their preparation are equally manifold. This short review presents some recent developments on the synthesis of deoxypropionate units involving, besides iterative and non-iterative routes, other methods such as stereoselective Mukaiyama reactions or lithiation–borylation–protodeboronation sequences. 1 Introduction 2 Biosynthesis of Deoxypropionates 3 Iterative Synthetic Methods 3.1 Conjugate Addition of Cuprates 3.2 Copper-Catalyzed Conjugate Additions 3.3 Copper-Mediated Allylic Substitution 3.4 Myers Alkylation 3.5 Zirconium-Catalyzed Carboalumination 3.6 Homologation of Boronates with Organolithiums 4 Non-Iterative Methods 4.1 Enzymatic Desymmetrization 4.2 Ex Chiral Pool Synthesis from Wax Esters 4.3 Ex Chiral Pool Synthesis from the Roche Ester 4.4 Sequential [3,3]-Sigmatropic Rearrangement and Catalytic Hydrogenation 5 Miscellaneous Methods 6 Conclusion

Zirconium-Catalyzed Carboalumination of α-Olefins and Chain Growth of Aluminum Alkyls: Kinetics and Mechanism

A mechanism based on Michaelis-Menten kinetics with competitive inhibition is proposed for both the Zr-catalyzed carboalumination of α-olefins and the Zr-catalyzed chain growth of aluminum alkyls from ethylene. AlMe(3) binds to the active catalyst in a rapidly maintained equilibrium to form a Zr/Al heterobimetallic, which inhibits polymerization and transfers chains from Zr to Al. The kinetics of both carboalumination and chain growth have been studied when catalyzed by [(EBI)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)]. In accord with the proposed mechanism, both reactions are first-order in [olefin] and [catalyst] and inverse first-order in [AlR(3)]. The position of the equilibria between various Zr/Al heterobimetallics and the corresponding zirconium methyl cations has been quantified by use of a Dixon plot, yielding K = 1.1(3) × 10(-4) M, 4.7(5) × 10(-4) M, and 7.6(7) × 10(-4) M at 40 °C in benzene for the catalyst species [rac-(EBI)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)], [Cp(2)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)], and [Me(2)C(Cp)(2)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)] respectively. These equilibrium constants are consistent with the solution behavior observed for the [Cp(2)Zr(μ-Me)(2)AlMe(2)][B(C(6)F(5))(4)] system, where all relevant species are observable by (1)H NMR. Alternative mechanisms for the Zr-catalyzed carboalumination of olefins involving singly bridged Zr/Al adducts have been discounted on the basis of kinetics and/or (1)H NMR EXSY experiments.

Synthesis of (+)‐Manoalide via a Copper(I)‐Mediated 1,2‐Metalate Rearrangement.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of (+)-manoalide via a copper(I)-mediated 1,2-metalate rearrangement.

An enantiospecific synthesis of the phospholipase A(2) inhibitor (+)-(4R)-manoalide is reported in which all 25 carbons of the sesterterpenoid skeleton are constructed from 3-furaldehyde, trimethylalane, oxirane, CO, beta-ionone, and propargyl bromide. The overall yield for the longest linear sequence (12 steps) is 12%. Key steps include (a) a zirconium-catalyzed carboalumination reaction to construct the C10-C11 trisubstituted alkene, (b) a Cu(I)-mediated 1,2-metalate rearrangement to construct the C6-C7 trisubstituted alkene, (c) a Sharpless kinetic resolution to secure the (4R)-stereochemistry, (d) generation of a 5-stannyl-2,3-dihydrofuran by Mo-catalyzed cycloisomerization of a homopropargylic alcohol, and (e) construction of the hydroxyfuranone ring by photooxidation of a silylfuran.

Increased Felkin—Anh Selectivity in Nucleophilic Additions to α‐Chiral Aldehydes Using Vinylalanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Increased Felkin–Anh selectivity in nucleophilic additions to α-chiral aldehydes using vinylalanes

Vinylalanes, prepared from the zirconium-catalyzed carboalumination of alkynes, were added directly to aldehydes bearing an alpha chiral carbon to give good yields of the corresponding alcohols. The addition was more stereoselective than the addition of the corresponding vinyllithium or vinylmagnesium bromide.

Zirconium-catalyzed carboalumination of alkynes and enynes as a route to aluminacycles and their conversion to cyclic organic compounds

Aluminacyclopentenes, obtainable via Zr-catalyzed cyclic carboalumination with Et3Al and alkynes or enynes, can be converted to the corresponding cyclopentenones and alkenylcyclopropanes by treatment with CO2 and BrCH2OCH3, respectively.

Total synthesis of FK-506. Part 1: Construction of the C16–C34 fragment

The C23–C27 1,3-diol was constructed via either Brown's crotylation - osmylation or regionand stereoselective opening of an 2,3-anhydro-β-ribofuranoside derived from D-xylofuranose. Lewis acid catalyzed epoxide opening with a protected lithiofurfural alcohol followed by oxidative spiroketalization established the C21–C24 spiroketal as a masked α′-allyl aldol. The C19–C20 tri-substituted olefin was synthesized via zirconium catalyzed carboalumination - in situ transmetalation with a higher order cuprate, followed by stereoselective conjugate addition to a spiroenone. The C27–C28 tri-substituted olefin was formed either via coupling of a methyl cuprate with an enoltriflate, mediated by sonication, or via direct coupling between the C17-aldehyde and the C28-vinyl magnesium bromide.

Multiple Mechanistic Pathways for Zirconium-Catalyzed Carboalumination of Alkynes. Requirements for Cyclic Carbometalation Processes Involving C−H Activation

The reactions of internal and terminal alkynes with organoalanes containing Et, n-Pr, and i-Bu groups in the presence of Cp2ZrCl2 and MeZrCp2Cl were investigated with the goal of clarifying mechanistic details of some representative cases. Three fundamentally different processes, i.e., (i) C−M bond addition without C−H activation in the alkyl group, (ii) cyclic C−M bond addition via C−H activation, and (iii) hydrometalation, have been observed, and the courses of these reactions significantly depend on (i) the nature and number of alkyl groups in organoalanes, (ii) their amounts, and (iii) solvents. The reaction of alkynes with Et3Al in the presence of 0.1 equiv of Cp2ZrCl2 in nonpolar solvents, e.g., hexanes, proceeds via C−H activation to give the corresponding aluminacyclopentenes. Investigation of the reaction of 5-decyne with 1−3 equiv of Et3Al and 1 equiv of Cp2ZrCl2, which gave mono-, di-, or trideuterated (Z)-5-ethyl-5-decene as shown in Scheme 10, together with the previously reported structural ...

Synthesis of β,γ-unsaturated amino acid derivatives by alkyne carbometalation-palladium catalyzed coupling with 2-aza-π-allyl palladium complexes

Zirconium-catalyzed carboalumination of terminal or symmetrical internal alkynes followed by palladium-catalyzed coupling of the resulting vinylalane with Schiff base acetate 1 gives protected β,γ-unsaturated amino acid derivatives (vinylglycines) 6.

Synthesis of (6E)-8-Thia- and (14E)-13-Thia-2,3-oxidosqualene: Inhibitors of 2,3-Oxidosqualene-Lanosterol Cyclase

Synthesis of (6E)-8-thia-2,3-oxidosqualene (22) and (14E)-13-thia-2,3-oxidosqualene (34) as inhibitors of 2,3-oxidosqualene-lanosterol cyclase are reported. Synthesis of 22 required the stereospecific generation of a vinyl sulfide. This was achieved by a new coupling of a benzenethiosulfonate (15) and a lithiated vinyl iodide (18). Synthesis of 34 involved similar coupling of benzenethiosulfonate 29 with lithium reagent obtained from vinyl iodide 33. The required (E)-vinyl iodides 18 and 33 were prepared by zirconium-catalyzed carboalumination of 4-pentyn-1-ol, (16) and 2,6-dimethyl-2(E),6(E)-dien-10-yne (32) respectively. Both 22 and 34 inhibited 2,3-oxidosqualene-lanosterol cyclase from Candida albicans with IC 50 values of 0.68 and 45 μM, respectively

A versatile and selective route to difunctional trisubstituted (E)-alkene synthons via zirconium-catalyzed carboalumination of alkynes

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA versatile and selective route to difunctional trisubstituted (E)-alkene synthons via zirconium-catalyzed carboalumination of alkynesCynthia L. Rand, David E. Van Horn, Mark W. Moore, and Eiichi NegishiCite this: J. Org. Chem. 1981, 46, 20, 4093–4096Publication Date (Print):September 1, 1981Publication History Published online1 May 2002Published inissue 1 September 1981https://doi.org/10.1021/jo00333a041RIGHTS & PERMISSIONSArticle Views2056Altmetric-Citations139LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (541 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts

Mechanism of the zirconium-catalyzed carboalumination of alkynes. Evidence for direct carboalumination

Mechanism of the zirconium-catalyzed carboalumination of alkynes. Evidence for direct carboalumination

A Selective and Efficient Synthesis of (E)-4-Methyl-3-alken-1-ols via Zirconium-Catalyzed Carboalumination of Terminal Alkynes

A Selective and Efficient Synthesis of (<i>E</i>)-4-Methyl-3-alken-1-ols via Zirconium-Catalyzed Carboalumination of Terminal Alkynes