Allylic Boronates Research Articles

Cu-catalyzed enantioselective assembly of axially chiral allylic boronates

Cu-catalyzed enantioselective assembly of axially chiral allylic boronates

Direct Asymmetric Synthesis of α-Aminoimines from 1,2-Bis-N-Sulfinylimines by Using Allyl Boronic Acids.

A unique direct asymmetric synthesis of α-aminoimines is realized, through rapid and exclusive mono-allylation of chiral bis-N-sulfinylimines using allylboronic acids. The highly selective allylation was possible as electrophilic imine functional group in the product α-aminoimines remained unreactive towards allyl boronic acid nucleophiles. Notably, by varying the geometry and chiral auxiliary, all four isomers of the α-aminoimines were accessed from readily available precursors. A range of allyl nucleophiles, which are tricky to generate by other means possessing highly reactive functional groups also took part in this reaction, expanding the scope further. The applicability of the products α-aminoimines were further demonstrated by accessing a range of structurally diverse chiral cyclic and acyclic 1,2-diamines bearing adjacent stereocenters through addition of a second nucleophile or aza-Prins-type cyclization by exploiting the nucleophilicity of the tethered alkene moiety. Moreover, the leaving group aptitude of sulfinyl auxiliary attached to imine, was exploited to access valuable chiral α-aminonitriles under thermal conditions without employing any reagents. Detailed DFT calculation revealed a chair-like transition state likely operating for the allylboration reaction across imine.

Bis(pentafluorophenyl)borane catalyzed atom-economic formation of alkenyl- and (homo)allyl boronates from dienes and boronic esters

The transition metal-free, atom-economic formation of cyclic alkenylboronates with normal ring size and (homo)allylboronates from dienes and dioxaborolanes catalyzed by bis(pentafluorophenyl)borane is reported.

Electrochemical stereoselective borylation of Morita-Baylis-Hillman adducts to functionalized allylic boronates.

Herein, we disclose a highly efficient and facile electrochemical borylation of Morita-Baylis-Hillman adducts without using any metal catalyst. This methodology demonstrates excellent regio- and stereo-selectivity, leading to a wide range of functionalized E-allylic boronates, including derivatives of ibuprofen and menthol. Under mild and straightforward conditions, this redox-neutral reaction, combined with the scalability and synthetic applications of the allylic boronate esters, underscores its potential for a wide range of applications in organic synthesis.

Direct Light-Enabled Access to α-Boryl Radicals: Application in the Stereodivergent Synthesis of Allyl Boronic Esters.

Operationally simple strategies to assemble boron containing organic frameworks are highly enabling in organic synthesis. While conventional retrosynthetic logic has engendered many platforms focusing on the direct formation of C-B bonds, α-boryl radicals have recently reemerged as versatile open-shell alternatives to access organoborons via adjacent C-C bond formation. Direct light-enabled α-activation is currently contingent on photo- or transition metal-catalysis activation to efficiently generate radical species. Here, we disclose a facile activation of α-halo boronic esters using only visible light and a simple Lewis base to enable homolytic scission. Intermolecular addition to styrenes facilitates the rapid construction of highly versatile E-allylic boronic esters. The simplicity of activation permits the strategic merger of this construct with selective energy transfer catalysis to enable the complimentary stereodivergent synthesis of Z-allylic boronic esters.

Direct Light‐Enabled Access to α‐Boryl Radicals: Application in the Stereodivergent Synthesis of Allyl Boronic Esters**

AbstractOperationally simple strategies to assemble boron containing organic frameworks are highly enabling in organic synthesis. While conventional retrosynthetic logic has engendered many platforms focusing on the direct formation of C−B bonds, α‐boryl radicals have recently reemerged as versatile open‐shell alternatives to access organoborons via adjacent C−C bond formation. Direct light‐enabled α‐activation is currently contingent on photo‐ or transition metal‐catalysis activation to efficiently generate radical species. Here, we disclose a facile activation of α‐halo boronic esters using only visible light and a simple Lewis base to enable homolytic scission. Intermolecular addition to styrenes facilitates the rapid construction of highly versatileE‐allylic boronic esters. The simplicity of activation permits the strategic merger of this construct with selective energy transfer catalysis to enable the complimentary stereodivergent synthesis ofZ‐allylic boronic esters.

Asymmetric Synthesis of α-Methylene-γ-Butyrolactones via Tandem Allylboration/Lactonization: a Kinetic Resolution Process.

The α-methylene-γ-butyrolactone motif is a widely encountered unit in many natural products and pharmaceutical compounds. Herein, a practical and efficient synthesis of α-methylene-γ-butyrolactones from readily available allylic boronates and benzaldehyde derivatives was developed with chiral N,N'-dioxide/AlIII complex as the catalyst. The key success of this transformation was the kinetic resolution of allylboration intermediate via asymmetric lactonization. This protocol enabled to assemble all of four stereoisomers from the same set of starting materials upon variable lactonization. Taking advantage of the current method as the key step, catalytic asymmetric total synthesis of eupomatilones 2, 5, and 6 was accomplished. Control experiments were carried out to probe into the tandem reaction as well as the origin of stereoselectivities.

Asymmetric Synthesis of α‐Methylene‐γ‐Butyrolactones via Tandem Allylboration/Lactonization: a Kinetic Resolution Process

AbstractThe α‐methylene‐γ‐butyrolactone motif is a widely encountered unit in many natural products and pharmaceutical compounds. Herein, a practical and efficient synthesis of α‐methylene‐γ‐butyrolactones from readily available allylic boronates and benzaldehyde derivatives was developed with chiral N,N′‐dioxide/AlIII complex as the catalyst. The key success of this transformation was the kinetic resolution of allylboration intermediate via asymmetric lactonization. This protocol enabled to assemble all of four stereoisomers from the same set of starting materials upon variable lactonization. Taking advantage of the current method as the key step, catalytic asymmetric total synthesis of eupomatilones 2, 5, and 6 was accomplished. Control experiments were carried out to probe into the tandem reaction as well as the origin of stereoselectivities.

Cobalt-Catalyzed Regiodivergent Ring-Opening Dihydroboration of Arylidenecyclopropanes to Access Skipped Diboronates.

Ligand-controlled regiodivergent cobalt-catalyzed ring-opening dihydroboration of arylidenecyclopropanes is developed to access synthetically versatile skipped diboronates with catalysts generated in situ from Co(acac)2 and dpephos or xantphos. A variety of arylidenecyclopropanes reacted with pinacolborane (HBpin) to form the corresponding 1,3- or 1,4-diboronates in high isolated yields and with high regioselectivity. Skipped diboronate products from these reactions can undergo various transformations to allow selective installation of two different functional groups along alkyl chains. Mechanistic studies suggest that these reactions combine cobalt-catalyzed ring-opening hydroboration of arylidenecyclopropanes and hydroboration of homoallylic or allylic boronate intermediates.

Cobalt‐Catalyzed Regiodivergent Ring‐Opening Dihydroboration of Arylidenecyclopropanes to Access Skipped Diboronates

AbstractLigand‐controlled regiodivergent cobalt‐catalyzed ring‐opening dihydroboration of arylidenecyclopropanes is developed to access synthetically versatile skipped diboronates with catalysts generated in situ from Co(acac)2 and dpephos or xantphos. A variety of arylidenecyclopropanes reacted with pinacolborane (HBpin) to form the corresponding 1,3‐ or 1,4‐diboronates in high isolated yields and with high regioselectivity. Skipped diboronate products from these reactions can undergo various transformations to allow selective installation of two different functional groups along alkyl chains. Mechanistic studies suggest that these reactions combine cobalt‐catalyzed ring‐opening hydroboration of arylidenecyclopropanes and hydroboration of homoallylic or allylic boronate intermediates.

Photocatalyzed regioselective hydrosilylation for the divergent synthesis of geminal and vicinal borosilanes

Geminal and vicinal borosilanes are useful building blocks in synthetic chemistry and material science. Hydrosilylation/hydroborylation of unsaturated systems offer expedient access to these motifs. In contrast to the well-established transition-metal-catalyzed methods, radical approaches are rarely explored. Herein we report the synthesis of geminal borosilanes from α-selective hydrosilylation of alkenyl boronates via photoinduced hydrogen atom transfer (HAT) catalysis. Mechanistic studies implicate that the α-selectivity originates from a kinetically favored radical addition and an energetically favored HAT process. We further demonstrate selective synthesis of vicinal borosilanes through hydrosilylation of allyl boronates via 1,2-boron radical migration. These strategies exhibit broad scopes across primary, secondary, and tertiary silanes and various boron compounds. The synthetic utility is evidenced by access to multi-borosilanes in a diverse fashion and scaling up by continuous-flow synthesis.

Organophosphorus-Catalyzed Borylative Ring-Opening of Vinylcyclopropanes: A Stereoselective Route to δ-Valerolactones

We report an operationally simple route to δ-valerolactones through an organophosphorus-catalyzed borylative ring-opening/allylation of vinylcyclopropanes providing δ-hydroxy esters stereoselectively. The δ-hydroxy esters were lactonized to obtain densely substituted δ-valerolactones. The present methodology exhibited enhanced functional group tolerance compared to the existing metal-mediated methods. A plausible mechanism for borylative ring-opening reaction has been suggested. 31P NMR studies indicated the involvement of a phosphonium zwitterionic species. The synthetic utility of the intermediate allyl boronates was demonstrated.

Copper(I)-Catalyzed Regio- and Stereoselective Silaboration of Terminal Allenes.

Organic compounds bearing both silyl and boryl groups are important building blocks in organic synthesis because of the adequate reactivity of the silyl and boryl groups and high stereospecificity in their derivatization reactions. The difference in reactivity between the silyl and boryl groups enables stepwise derivatization of these groups to afford complex molecules. Here, we report the copper(I)-catalyzed silaboration of terminal allenes to produce multisubstituted allylic boronates embedded with an alkenyl silane structure. The reaction can proceed with a variety of allenes and silylboranes. Furthermore, the silyl and boryl groups were successfully converted into other functional groups, while retaining the stereochemistry of the alkene moiety.

Catalyst Controlled Site- and Stereoselective Rhodium(II) Carbene C(sp3)-H Functionalization of Allyl Boronates.

Rhodium(II) catalyst-controlled site- and stereoselective carbene insertion into the distal allylic C(sp3)-H bond of allyl boronates is reported. The optimum chiral catalyst for this reaction is Rh2(S-TPPTTL)4. The fidelity and asymmetric induction of this catalytic transformation allows for a highly diastereoselective and enantioselective C-C bond formation without interference from the allyl boronate functionality. The resulting functionalized allyl boronates are susceptible to stereoselective allylations, generating products with control of stereochemistry at four contiguous stereogenic centers.

1,1-Regioselective alkenylboration of styrenes enabled by palladium catalysis

Despite the 1,2-difunctionalization reactions of styrenes have been well developed, the 1,1-regioselective addition reaction remains challenging. We disclose herein a palladium-catalyzed, highly 1,1-regioselective alkenylboration of styrenes by using alkenyl triflates and a diboron reagent as the coupling partners. A wide scope of styrenes derivatives and alkenyl triflates participate this reaction to provide the corresponding allyl boronates with high regioisomeric ratios. The success of this reaction is ascribed to the application of 1,10-phenanthroline-derivated ligand and the addition of ammonium chloride salt. Moreover, acrylate esters can also selectively afford the 1,1-alkenylboration products under the same reaction conditions.

Unusual Enantiodivergence in Chiral Brønsted Acid-Catalyzed Asymmetric Allylation with β-Alkenyl Allylic Boronates.

We report herein a rare example of enantiodivergent aldehyde addition with β-alkenyl allylic boronates via chiral Brønsted acid catalysis. 2,6-Di-9-anthracenyl-substituted chiral phosphoric acid-catalyzed asymmetric allylation using β-vinyl substituted allylic boronate gave alcohols with R absolute configuration. The sense of asymmetric induction of the catalyst in these reactions is opposite to those in prior reports. Moreover, in the presence of the same acid catalyst, the reactions with β-2-propenyl substituted allylic boronate generated homoallylic alcohol products with S absolute configuration. Unusual substrate-catalyst C-H⋅⋅⋅π interactions in the favoured reaction transition state were identified as the origins of observed enantiodivergence through DFT computational studies.

Unusual Enantiodivergence in Chiral Brønsted Acid‐Catalyzed Asymmetric Allylation with β‐Alkenyl Allylic Boronates

AbstractWe report herein a rare example of enantiodivergent aldehyde addition with β‐alkenyl allylic boronates via chiral Brønsted acid catalysis. 2,6‐Di‐9‐anthracenyl‐substituted chiral phosphoric acid‐catalyzed asymmetric allylation using β‐vinyl substituted allylic boronate gave alcohols with R absolute configuration. The sense of asymmetric induction of the catalyst in these reactions is opposite to those in prior reports. Moreover, in the presence of the same acid catalyst, the reactions with β‐2‐propenyl substituted allylic boronate generated homoallylic alcohol products with S absolute configuration. Unusual substrate‐catalyst C−H⋅⋅⋅π interactions in the favoured reaction transition state were identified as the origins of observed enantiodivergence through DFT computational studies.

Differential Dihydrofunctionalization: A Dual Catalytic Three-Component Coupling of Alkynes, Alkenyl Bromides, and Pinacolborane.

A new method for differential dihydrofunctionalization of terminal alkynes enables the synthesis of allylic boronate esters through reductive three-component coupling of terminal alkynes, alkenyl bromides, and pinacolborane. The transformation is promoted by cooperative action of a copper/palladium catalyst system and results in hydrofunctionalization of both π-bonds of an alkyne. The synthesis of allylic boronate esters can be accomplished in the presence of a wide range of functional groups, including, esters, nitriles, alkyl halides, sulfonyl esters, acetals, protected terminal alkynes, aryl halides, and silyl ethers. Mechanistic experiments reveal the importance of subtle ligand effects on the performance of the palladium co-catalyst.

Differential Dihydrofunctionalization: A Dual Catalytic Three‐Component Coupling of Alkynes, Alkenyl Bromides, and Pinacolborane

AbstractA new method for differential dihydrofunctionalization of terminal alkynes enables the synthesis of allylic boronate esters through reductive three‐component coupling of terminal alkynes, alkenyl bromides, and pinacolborane. The transformation is promoted by cooperative action of a copper/palladium catalyst system and results in hydrofunctionalization of both π‐bonds of an alkyne. The synthesis of allylic boronate esters can be accomplished in the presence of a wide range of functional groups, including, esters, nitriles, alkyl halides, sulfonyl esters, acetals, protected terminal alkynes, aryl halides, and silyl ethers. Mechanistic experiments reveal the importance of subtle ligand effects on the performance of the palladium co‐catalyst.

Merging Halogen-Atom Transfer (XAT) and Copper Catalysis for the Modular Suzuki-Miyaura-Type Cross-Coupling of Alkyl Iodides and Organoborons.

We report here a mechanistically distinct approach to achieve Suzuki–Miyaura-type cross-couplings between alkyl iodides and aryl organoborons. This process requires a copper catalyst but, in contrast with previous approaches based on palladium and nickel systems, does not utilizes the metal for the activation of the alkyl electrophile. Instead, this strategy exploits the halogen-atom-transfer ability of α-aminoalkyl radicals to convert secondary alkyl iodides into the corresponding alkyl radicals that then are coupled with aryl, vinyl, alkynyl, benzyl, and allyl boronate species. These novel coupling reactions feature a simple setup and conditions (1 h at room temperature) and facilitate access to privileged motifs targeted by the pharmaceutical sector.