Vinylaluminum Reagents Research Articles

Cu-Catalyzed electrophilic amination of internal alkynes via hydroalumination.

A straightforward and efficient method for the synthesis of 1,2-diaryl-substituted enamines through the Cu-catalyzed electrophilic amination reaction of O-benzoyl hydroxylamines with vinylaluminum reagents generated in situ from the Ni-catalyzed hydroalumination of readily accessible internal aryl acetylenes is described. The amination is catalyzed by 1 mol% CuCl without any additive at ambient temperature to afford new versatile enamines in good yield (61-91%) with high selectivity (>98% E-enamine).

Chiral Aluminum Catalyst System for the Enantioselective Addition of Vinylaluminum Reagents to Aldehydes: Metal Controlled Reversal of Enantioselectivity

AbstractA chiral aluminum catalyst system has been developed for the enantioselective vinylation of aldehydes. β,β‐Disubstituted (E)‐vinylaluminum reagents, generated regio‐ and stereoselectively by the carboalumination of terminal alkynes with trimethylalumunim (Me3Al), were used straightforwardly without transmetalation to vinyltitanium reagents in the subsequent enantioselective addition to aldehydes with a DPP‐H8‐BINOL‐derived chiral aluminum catalyst at low catalyst loading (5 mol%). The reaction afforded the corresponding enantiomerically enriched secondary allylic alcohols with a reversal of the selectivity observed in closely related reactions catalyzed by a chiral titanium complex derived from the same ligand.magnified image

ChemInform Abstract: Catalytic Enantioselective Synthesis of α‐Substituted Secondary Allylic Alcohols from Terminal Alkynes and Aldehydes via Vinylaluminum Reagents.

AbstractThe use of Me2AlH is essential in the Ni‐catalyzed hydroalumination step to generate reactivity‐tuned vinylaluminum reagents not able to reduce the aldehyde starting material.

Catalytic Enantioselective Synthesis of α‐Substituted Secondary Allylic Alcohols from Terminal Alkynes and Aldehydes via Vinylaluminum Reagents

One-pot procedure: A general method for the highly enantioselective synthesis of α-substituted allylic alcohols has been developed starting from readily available terminal alkynes and aldehydes and proceeding via vinylaluminum reagents (see scheme, dppp=1,3-bis(diphenylphosphino)propane). The use of Me2AlH is essential in the Ni-catalyzed hydroalumination step to generate vinylaluminum reagents that cannot reduce the aldehyde.

ChemInform Abstract: Formation of Vinyl‐, Vinylhalide‐ or Acyl‐Substituted Quaternary Carbon Stereogenic Centers Through NHC—Cu‐Catalyzed Enantioselective Conjugate Additions of Si‐Containing Vinylaluminums to β‐Substituted Cyclic Enones.

A catalytic method for enantioselective conjugate addition (ECA) of Si-containing vinylaluminum reagents to β-substituted cyclopentenones and cyclohexenones is described. Reactions are promoted by 1.0−5.0 mol % of a bidentate NHC−Cu complex, which is prepared from air-stable CuCl2•2H2O and used in situ, and typically proceed to completion within 15−20 min. The requisite vinylmetals are generated efficiently by a site-selective hydroalumination of an alkyne with dibal-H. The desired products, containing a quaternary carbon stereogenic center, are obtained in 48−95% yield after purification and in 89:11 to >98:2 enantiomer ratio (er). The vinylsilane moiety within the products can be functionalized to afford acyl, vinyliodide, or desilylated alkenes in 67% to >98% yield and with >90% retention of the alkene’s stereochemical identity. The utility of the catalytic process is illustrated in the context of a concise enantioselective synthesis of riccardiphenol B.

Enantioselective Conjugated Addition of Vinylaluminums to Cyclic Enones

The development of transition-­metal-catalyzed enantioselective reactions allowing the formation of quaternary stereogenic centers is a challenging task. Herein, the authors report a highly enantioselective conjugated addition of Si-substituted vinylaluminum reagents to five- and six-membered cyclic β-substituted enones of type 1. A chiral bidentate NHC-copper complex has been identified to facilitate the desired transformation of 1 into 2 with good to excellent yields and enantioselectivities.

ChemInform Abstract: Synthesis of Quaternary Carbon Stereogenic Centers Through Enantioselective Cu‐Catalyzed Allylic Substitutions with Vinylaluminum Reagents.

AbstractCatalytic enantioselective allylic substitution reactions using alkyl‐ and aryl‐substituted vinylaluminum reagents afford 1,4‐dienes containing a quaternary carbon stereogenic center at C‐3, also by addition of a vinyl unit.

Formation of vinyl-, vinylhalide- or acyl-substituted quaternary carbon stereogenic centers through NHC-Cu-catalyzed enantioselective conjugate additions of Si-containing vinylaluminums to β-substituted cyclic enones.

A catalytic method for enantioselective conjugate addition (ECA) of Si-containing vinylaluminum reagents to β-substituted cyclopentenones and cyclohexenones is described. Reactions are promoted by 1.0-5.0 mol % of a bidentate NHC-Cu complex, which is prepared from air-stable CuCl(2)•2H(2)O and used in situ, and typically proceed to completion within 15-20 min. The requisite vinylmetals are generated efficiently by a site-selective hydroalumination of an alkyne with dibal-H. The desired products, containing a quaternary carbon stereogenic center, are obtained in 48-95% yield after purification and in 89:11 to >98:2 enantiomer ratio (er). The vinylsilane moiety within the products can be functionalized to afford acyl, vinyliodide, or desilylated alkenes in 67% to >98% yield and with >90% retention of the alkene's stereochemical identity. The utility of the catalytic process is illustrated in the context of a concise enantioselective synthesis of riccardiphenol B.

Synthesis of quaternary carbon stereogenic centers through enantioselective Cu-catalyzed allylic substitutions with vinylaluminum reagents.

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C-C bond-forming transformations are promoted by 0.5-2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66-97% yield of isolated products) and in high site (>98% S(N)2')- and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometalations and Cu-catalyzed C-C bond-forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol.

ChemInform Abstract: Stereoisomerically Pure Trisubstituted Vinylaluminum Reagents and Their Utility in Copper‐Catalyzed Enantioselective Synthesis of 1,4‐Dienes Containing Z or E Alkenes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Stereoisomerically Pure Trisubstituted Vinylaluminum Reagents and their Utility in Copper‐Catalyzed Enantioselective Synthesis of 1,4‐Dienes Containing Z or E Alkenes

Catalytic enantioselective addition of vinyl groups to C-based electrophiles constitutes a versatile class of C–C bond forming processes.[1–3] We recently reported that vinylaluminum reagents, generated through reactions of alkyl- or alkenyl-substituted terminal alkynes with commercially available and inexpensive diisobutylaluminum hydride (dibal-H), can be used in site- and enantioselective Cu-catalyzed allylic alkylations.[4] The above protocol, however, suffers from two notable deficiencies. First, cis vinylmetals cannot be accessed (>98% trans product formed due to syn addition of Al–H to terminal alkynes). Second, aryl-substituted vinylaluminums cannot be utilized since the corresponding hydroaluminations are inefficient.[5] Herein, we present solutions to the above shortcomings through efficient, site- and stereoselective preparation of vinylaluminum reagents by reactions of Si-substituted alkynes with dibal-H. The vinylmetals can be used in situ in site- and enantioselective Cu-catalyzed allylic alkylations.[6] Enantiomerically enriched vinylsilanes are proto-desilylated with trifluoroacetic acid (TFA), affording the derived Z or E alkenes typically as a single stereoisomer in up to >99:1 enantiomeric ratio (e.r.).

Stereoisomerically Pure Trisubstituted Vinylaluminum Reagents and their Utility in Copper‐Catalyzed Enantioselective Synthesis of 1,4‐Dienes Containing Z or E Alkenes

Stereoisomerically Pure Trisubstituted Vinylaluminum Reagents and their Utility in Copper‐Catalyzed Enantioselective Synthesis of 1,4‐Dienes Containing <i>Z</i> or <i>E</i> Alkenes

Highly Enantioselective Vinyl Additions of Vinylaluminum to Ketones Catalyzed by a Titanium(IV) Catalyst of (S)-BINOL

We report a novel asymmetric addition of vinyl group to ketones using vinylaluminum reagents catalyzed by in situ prepared Ti(O(i)Pr)(4) complexes of (S)-BINOL to afford diversified tertiary allylic alochols. Varieties of aromatic ketones bearing either an electron-donating or an electron-withdrawing substituent on the aromatic ring were examined to afford products in excellent enantioselectivities of up to 98% ee with high yields. A 10-fold scale-up reaction afforded the product in a similar yield with a comparable enantioselectivity. More importantly, additions of a variety of vinyl reagents including functionalized vinyls were demonstrated, affording tertiary allylic alcohols with good to excellent enantioselectivities of up to 96% ee.

ChemInform Abstract: Highly Site‐ and Enantioselective Cu‐Catalyzed Allylic Alkylation Reactions with Easily Accessible Vinylaluminum Reagents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly Site- and Enantioselective Cu-Catalyzed Allylic Alkylation Reactions with Easily Accessible Vinylaluminum Reagents

An efficient method for catalytic asymmetric allylic alkylation (AAA) of allylic phosphates with vinylaluminum reagents is reported. The vinylmetal reagents are prepared by reaction of commercially available DIBAL-H and a terminal alkyne. The resulting vinylaluminum reagent can be used directly, without isolation or purification. AAA reactions are promoted in the presence of 0.5−2.5 mol % of a readily available chiral N-heterocyclic carbene (NHC) complex and 1−5 mol % commercially available and air stable Cu salt (CuCl2·2H2O). The desired products are typically obtained within 2−12 h in 74% to 95% isolated yield, 77% to >98% ee, and in >98% E selectivity; >98% SN2‘ selectivity is obtained in all but one instance (90%). The hydroalumination/catalytic AAA sequence can be performed in a single vessel, on gram scale.

Vinylalumination for the Synthesis of Functionalized Allyl Alcohols, Vinylepoxides, and α‐Alkylidene‐β‐hydroxy‐γ‐lactones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Vinylalumination for the synthesis of functionalized allyl alcohols, vinylepoxides, and alpha-alkylidene-beta-hydroxy-gamma-lactones.

A modified hydroalumination protocol for the preparation of [alpha-(ethoxycarbonyl)vinyl]diisobutylaluminum and its beta-methyl or -phenyl analogues was developed. These vinylaluminum reagents react with aldehydes and ketones to provide the corresponding functionalized allyl alcohols in good to excellent yields. Perfluoroalkyl and -aryl carbonyl compounds, alpha-keto esters, alpha-acyl cyanides, and alpha-acetylenic ketones provide the corresponding alpha-hydroxyalkenes in high yields. The allyl alcohol product ratios from the vinylalumination of unsymmetrical alpha-diketones with [alpha-(ethoxycarbonyl)vinyl]diisobutylaluminum and its beta-methyl or -phenyl analogues depend on the steric and electronic environments of the ketones as well as the reagents. The products from the vinylalumination of alpha-bromoaldehydes and -ketones were cyclized with K2CO3 or KF under nonaqueous conditions to provide functionalized vinylepoxides in high yields. Vinylaluminations of keto-protected pyruvaldehyde provided the products, which were converted to alpha-alkylidene-beta-hydroxy-gamma-lactones.

Synthesis of the Azatricyclic Core of FR901483 by Bridgehead Vinylation via an anti‐Bredt Iminium Ion.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of the azatricyclic core of FR901483 by bridgehead vinylation via an anti-Bredt iminium ion

We have developed an alternative route to the azatricyclic core skeleton of FR901483 based on vinylation at the bridgehead position of 2-azabicyclo[3.3.1]nonane via an anti-Bredt iminium ion using vinylaluminum reagents.

Applications of the β-Azidonation Reaction to Organic Synthesis. α,β-Enones, Conjugate Addition, and γ-Lactam Annulation

The s-azido functionalization reaction provides a mechanistically different enone synthesis that involves treatment of 2 with fluoride anion to effect desilylation and concomitant s-elimination to give 3. Table 1 lists a number of examples of the direct conversion of a TIPS enol ether into the corresponding a,s-enone via a s-azido TIPS enol ether. The s-azido group can be ionized with Me3Al or Me2AlCl and the intermediate enonium ion trapped by a variety of nucleophiles such as an allylstannane, electron-rich aromatics, TMS enol ethers, Et2AlCN, Me2AlCCR, Me4AlLi, and vinylaluminum reagents to give the products listed in Table 2. The diastereoselectivity of the reaction of a 4-substituted enonium ion with indole shows an unusual increase of selectivity with increasing temperature. Reduction of the azide 2 provides access to s-amino TIPS enol ethers 5, which, for example, can be converted into a cinnamide derivative and cyclized via a putative “ene” process into a ?-lactam.