Enantioselective Synthesis of Multisubstituted Allenes by Cooperative Cu/Pd‐Catalyzed 1,4‐Arylboration of 1,3‐Enynes

A cooperative Cu/Pd‐catalyzed enantioselective synthesis of multisubstituted allenes is established. By employing chiral sulfoxide phosphine (SOP)/Cu and PdCl₂(dppf) complexes as catalysts, the 1,4‐arylboration of 1,3‐enynes provides an efficient approach to trisubstituted chiral allenes with up to 92 % yield and 97:3 er. Furthermore, by using 2‐substituted 1,3‐enynes as substrates, the tetrasubstituted chiral allenes were successfully generated using this strategy. Finally, theoretical calculations indicate that the transmetallation of the allenylcopper species is the rate‐limiting step of this transformation.     

Halogenated salt assisted Cu-catalyzed asymmetric 1,4-borylstannation of 1,3-enynes: enantioselective synthesis of allenylstannes

An enantioselective 1,4-borylstannation of 1,3-enynes employed a chiral sulfoxide phosphine (SOP)/Cu complex as a catalyst, and the desired products, chiral allenylstannes, were first synthesized by asymmetric catalysis with satisfactory yields and enantioselectivies. In this protocol, a catalytic amount of additive, a halogenated salt, plays a crucial role in the success. Control experiments and theoretical studies disclosed that the four-membered ring transmetallation transition states which were stabilized by a halide anion are the key to yields and stereochemical outcomes.

An enantioselective 1,4-borylstannation of 1,3-enynes employed a chiral sulfoxide phosphine (SOP)/Cu complex as a catalyst, and the desired products, chiral allenylstannes, were first synthesized by asymmetric catalysis with satisfactory yields and enantioselectivies.     

Regiodivergent sulfonylarylation of 1,3-enynes via nickel/photoredox dual catalysis

Catalytic difunctionalization of 1,3-enynes represents an efficient and versatile approach to rapidly assemble multifunctional propargylic compounds, allenes and 1,3-dienes. Controlling selectivity in such addition reactions has been a long-standing challenging task due to multiple reactive centers resulting from the conjugated structure of 1,3-enynes. Herein, we present a straightforward method for regiodivergent sulfonylarylation of 1,3-enynes via dual nickel and photoredox catalysis. Hinging on the nature of 1,3-enynes, diverse reaction pathways are feasible: synthesis of α-allenyl sulfones via 1,4-sulfonylarylation, or preparation of (E)-1,3-dienyl sulfones with high chemo-, regio- and stereoselectivity through 3,4-sulfonylarylation. Notably, this is the first example that nickel and photoredox catalysis are merged to achieve efficient and versatile difunctionalization of 1,3-enynes.

A mild reaction protocol for regiodivergent sulfonylarylation of 1,3-enynes via dual nickel and photoredox catalysis has been developed, which led to efficient synthesis of α-allenyl sulfones or 1,3-dienyl sulfones.     

Heterogeneous Copper-Catalyzed Cross-Coupling for Sustainable Synthesis of Chiral Allenes: Application to the Synthesis of Allenic Natural Products

Classical Crabbé type S_N2' substitutions of propargylic substrates has served as one of the standard methods for the synthesis of allenes. However, the stereospecific version of this transformation often requires either stoichiometric amounts of organocopper reagents or special functional groups on the substrates, and the chirality transfer efficiency is also capricious. Herein, we report a sustainable methodology for the synthesis of diverse 1,3-di and tri-substituted allenes by using a simple and cheap cellulose supported heterogeneous nanocopper catalyst (MCC-Amp-Cu(I/II)). This approach represents the first example of heterogeneous catalysis for the synthesis of chiral allenes. High yields and excellent enantiospecificity (up to 97 % yield, 99 % ee) were achieved for a wide range of di- and tri-substituted allenes bearing various functional groups. It is worth noting that the applied heterogeneous catalyst could be recycled at least 5 times without any reduced reactivity. To demonstrate the synthetic utility of the developed protocol, we have applied it to the total synthesis of several chiral allenic natural products.     

Asymmetric dihydroxylation of disubstituted allenes

Asymmetric dihydroxylation of 1,1-disubstituted and 1,3-disubstituted allenes can be used to synthesize chiral α-hydroxy ketones. We have also obtained α,α′-dihydroxy ketones with high enantioselectivity from 1,3-disubstituted allenes. Low conversion of the dihydroxylation of chiral allenes can be used as a kinetic resolution of sterically hindered allenes.     

Highly Enantioselective Asymmetric Autocatalysis of Pyrimidin‐5‐yl Alkanol Induced by Chiral 1,3‐Disubstituted Hydrocarbon Allenes

1,3‐Disubstituted chiral allenes without any heteroatoms act as chiral initiators in the addition of (i‐Pr)₂Zn to pyrimidine‐5‐carbaldehyde to afford, in combination with the subsequent asymmetric autocatalysis, chiral pyrimidin‐5‐yl alkanols with up to 98% ee. The absolute configuration of the pyrimidin‐5‐yl alkanol formed depend on that of the chiral allene.     

Decarboxylative 1,4-carbocyanation of 1,3-enynes to access tetra-substituted allenes via copper/photoredox dual catalysis

We disclose herein the first example of merging photoredox catalysis and copper catalysis for radical 1,4-carbocyanations of 1,3-enynes. Alkyl N-hydroxyphthalimide esters are utilized as radical precursors, and the reported mild and redox-neutral protocol has broad substrate scope and remarkable functional group tolerance. This strategy allows for the synthesis of diverse multi-substituted allenes with high chemo- and regio-selectivities, also permitting late stage allenylation of natural products and drug molecules.

An efficient synthesis of multi-substituted allenes by metallaphotoredox-catalyzed decarboxylative 1,4-carbocyanation of 1,3-enynes is described.     

Construction of All-Carbon Chiral Quaternary Centers through CuI-Catalyzed Enantioselective Reductive Hydroxymethylation of 1,1-Disubstituted Allenes with CO2

A catalytic enantioselective construction of all-carbon chiral quaternary centers through reductive hydroxymethylation of 1,1-disubstituted allenes with CO₂ has been developed. In the presence of a copper/Mandyphos catalyst, CO₂ is transformed into an alcohol oxidation level by an asymmetric reductive C−C bond formation with allenes by using hydrosilane (HSi(OMe)₂Me) as a reductant. The resulting chiral homoallylic alcohols are versatile synthetic intermediates and can be conveniently converted into a variety of useful chiral chemicals.     

Palladium-catalyzed asymmetric hydrosilylation of 1,3-dienes

Advances in the palladium-catalyzed asymmetric hydrosilylation of 1,3-dienes are presented according to substrate types and chiral monophosphine ligands. Chiral monodentate phosphine ligands with a binaphthyl moiety have been proven to be the most efficient ligands for cyclic 1,3-dienes, and planar chiral ferrocenylmonophosphine ligands with two ferrocenyl moieties for linear 1,3-dienes. The ferrocenylmonophosphine ligands have expanded the substrate scope to 1,3-enynes in the asymmetric hydrosilylation. Palladium-catalyzed asymmetric hydrosilylation of 1,3-dienes and 1,3-enynes leads to the stereoselective synthesis of allylsilanes and allenylsilanes, respectively.     

Chiral Auxiliary Approach for Gold(I)-Catalyzed Cyclizations

Two different classes of stereoselective cyclizations have been developed using a chiral auxiliary approach with commercially available [JohnPhosAu(MeCN)SbF₆] as catalyst. First, a stereoselective cascade cyclization of 1,5-enynes was achieved using the Oppolzer camphorsultam as chiral auxiliary. In this case, a one-pot cyclization-hydrolysis sequence was developed to directly afford enantioenriched spirocyclic ketones. Then, the stereoselective alkoxycyclization of 1,6-enynes was mediated by an Evans-type oxazolidinone. A reduction-hydrolysis sequence was selected to remove the auxiliary to give enantioenriched β-tetralones. DFT studies confirmed that the steric clash between the chiral auxiliary and alkene accounts for the experimentally observed diastereoselective cyclization through the Si face.     

Synthesis of chiral allene moiety from Morita–Baylis–Hillman adduct of isatin derivatives via Claisen rearrangement

Chiral allenes are synthesized from Morita–Baylis–Hillman adduct of isatin derivatives via Claisen rearrangement for the first time. The chiral 1,3-substituted allene entity is achieved using (R)-but-3-yn-2-ol. The details of the work are elaborately discussed in this letter.     

Enantioselective construction of quaternary carbon centers by catalytic [2 + 2 + 2] cycloaddition of 1,6-enynes and alkynes

[reaction: see text] The enantioselective [2 + 2 + 2] cycloaddition of 1,6-enynes and alkynes using chiral rhodium catalysts gave cycloadducts containing quaternary carbon stereocenters. Both symmetrical and unsymmetrical alkynes and acetylene could be used as coupling partners, and the corresponding bicyclic cyclohexa-1,3-dienes were obtained in good to excellent ee.     

Kinetic Resolution of Azaarylethynyl Tertiary Alcohols by Chiral Brønsted Acid Catalysed Phosphine-Mediated Deoxygenation

A chiral Brønsted acid catalysed phosphine-mediated deoxygenation protocol is reported. This metal-free method provides a precise kinetic resolution platform for azaarylethynyl tertiary alcohols, which are a broad category of biologically and synthetically important azaarene derivatives. In addition to providing an efficient method for the first asymmetric preparation of these tertiary alcohols, the strategy facilitates the construction of azaaryl-functionalized allenes with good to excellent enantioselectivities. The high selectivity factors (s up to 235), broad substrate scope, and ability to convert azaaryl compounds into both chiral tertiary alcohols and allenes robustly underscore the efficiency and promising utility of this method. The practicability is further validated by the successful synthesis of deuterated allenes with high ee values and substantial incorporation of deuterium using inexpensive D₂O as the deuterium source.     

Rhodium-Catalyzed Pauson–Khand-Type Cyclization of 1,5-Allene-Alkynes: A Chirality Transfer Strategy for Optically Active Bicyclic Ketones

An efficient chirality transfer in the [RhCl(CO)₂]₂-catalyzed [2+2+1] cyclization of optically active axially chiral 1,3-disubstituted allenynes with CO to access optically active bicyclopentenone compounds has been developed. The distal C=C bond of allenes reacted with the alknye unit and CO to afford [4.3.0]-bicyclic products with high ee values under mild reaction conditions with an excellent selectivity.     

Z‐Selective Hydrothiolation of Racemic 1,3‐Disubstituted Allenes: An Atom‐Economic Rhodium‐Catalyzed Dynamic Kinetic Resolution

A Z‐selective rhodium‐catalyzed hydrothiolation of 1,3‐disubstituted allenes and subsequent oxidation towards the corresponding allylic sulfones is described. Using the bidentate 1,4‐bis(diphenylphosphino)butane (dppb) ligand, Z/E‐selectivities up to >99:1 were obtained. The highly atom‐economic desymmetrization reaction tolerates functionalized aromatic and aliphatic thiols. Additionally, a variety of symmetric internal allenes, as well as unsymmetrically disubstituted substrates were well tolerated, thus resulting in high regioselectivities. Starting from chiral but racemic 1,3‐disubstituted allenes a dynamic kinetic resolution (DKR) could be achieved by applying (S,S)‐Me‐DuPhos as the chiral ligand. The desired Z‐allylic sulfones were obtained in high yields and enantioselectivities up to 96 % ee.     

Copper‐Catalyzed Propargylic Substitution of Dichloro Substrates: Enantioselective Synthesis of Trisubstituted Allenes and Formation of Propargylic Quaternary Stereogenic Centers

An easy and versatile Cu‐catalyzed propargylic substitution process is presented. Using easily prepared prochiral dichloro substrates, readily available Grignard reagents together with catalytic amount of copper salt and chiral ligand, we accessed a range of synthetically interesting trisubstituted chloroallenes. Substrate scope and nucleophile scope are broad, providing generally high enantioselectivity for the desired 1,3‐substitution products. The enantioenriched chloroallenes could be further transformed into the corresponding trisubstituted allenes or terminal alkynes bearing all‐carbon quaternary stereogenic centers, through the copper‐catalyzed enantiospecific 1,1/1,3‐substitutions. The two successive copper‐catalyzed reactions could be eventually combined into a one‐pot procedure and different desired allenes or alkynes were obtained respectively with high enantiomeric excesses.     

Allenes and Dienes as Chiral Allylmetal Pronucleophiles in Catalytic Enantioselective C=X Addition: Historical Perspective and State-of-The-Art Survey

The use of allenes and 1,3-dienes as chiral allylmetal pronucleophiles in intermolecular catalytic enantioselective reductive additions to aldehydes, ketones, imines, carbon dioxide and other C=X electrophiles is exhaustively catalogued together with redox-neutral hydrogen auto-transfer processes. Coverage is limited to processes that result in both C−H and C−C bond formation. The use of alkynes as latent allylmetal pronucleophiles and multicomponent C=X allylations involving allenes and dienes is not covered. As illustrated in this review, the ability of allenes and 1,3-dienes to serve as tractable non-metallic pronucleophiles has evoked many useful transformations that have no counterpart in traditional allylmetal chemistry.     

Studies on ZnBr2-mediated synthesis of axially chiral aryl-substituted allenes from terminal alkynes,aromatic aldehydes and (S)-α,α-diphenylprolinol

The studies on the ZnBr₂-mediated synthesis of axially chiral aryl-substituted allenes from terminal alkynes, aromatic aldehydes, and commercially available chiral amine (S)-α,α-diphenylprolinol were conducted. Axially chiral aryl-substituted allenes can be obtained in moderate yields with up to 96% ee.     

Facile Stereoselective Synthesis of (E)-1-Arylseleno-Substituted 1,3-Enynes and Their Applications in Synthesis of (E)-Enediynes

(E)-1-Iodo-2-arylselenoethylenes 1 underwent the Sonogashira coupling reactions with terminal alkynes 2 to afford (E)-1-arylseleno-substituted 1,3-enynes 3 in high yields. (E)-1-Arylseleno-substituted 1,3-enynes 3 were coupled with alkynylmagnesium bromides 4 in the presence of a catalytic amount of NiCl₂(PPh₃)₂ to give stereoselectively (E)-enediynes 5 in good yields.     

1,3-Dipolar addition of nitrones to symmetrically substituted allenes: for the determination of absolute configuration of chiral allenes by NMR spectroscopy

5-Methyl-5-phenylpyrroline N-oxide was proved to be a useful 1,3-dipole for determining the absolute configuration of chiral allenes by means of NMR spectroscopy.