Allylboration Of Aldehydes Research Articles

Toward Multi‐Functionalized Organogermaniums: Diastereoselective Transformations of Germacycles Derived from Cheletropic Reactions of Boron‐Substituted Butadienes with Ge(II) Salts

The field of organogermanium in chemistry has recently attracted attention. Thanks to the inherent features of germanium (Ge), introducing Ge‐based substituents into organic frameworks has enhanced bioactivity and optoelectronic properties of molecules. Herein, the synthesis of multi‐functionalized organogermaniums using Ge(II) salts is reported. The germacycles having an allylboron moiety, which is derived from the (4+1) cycloadditions of the butadienes bearing a boronic ester moiety with Ge(II) salts, can be applied to further allylboration of aldehydes with perfect diastereoselectivity. The obtained allylated adducts enable access to π‐extended organogermaniums with the retention of the stereocenters.

Access to γ‐Iodo‐<i>gem</i>‐Diborylated Cyclopentanes and to Bicyclic Cyclopropanes

A formal atom transfer radical [3+2] annulation (ATRAn) reaction between different homoallyl radical precursors and 1,1‐diborylethene was developed. It provides a rapid access to polysubstituted cyclopentanes containing a gem‐diboronic ester moiety. The synthetic utility of theses uniquely functionalized 5‐membered rings is highlighted by their easy conversion to attractive borylated building blocks such as 1‐borylated bicyclo[3.1.0]hexanes. The ATRAn reaction was extended to homopropagylic radicals giving access to unique allylic gem‐diboronic esters that could be used in allylboration of aldehydes. Furthermore, this work highlights that 1,1‐diborylethene represents a synthetic equivalent to ketene, a so far elusive radical trap due to its daunting reactivity.

Palladium-Catalyzed Cascade Heck Coupling and Allylboration of Iododiboron Compounds via Diboryl Radicals.

Geminal bis(boronates) are versatile synthetic building blocks in organic chemistry. The fact that they predominantly serve as nucleophiles in the previous reports, however, has restrained their synthetic potential. Herein we disclose the ambiphilic reactivity of α-halogenated geminal bis(boronates), of which the first catalytic utilization was accomplished by merging a formal Heck cross-coupling with a highly diastereoselective allylboration of aldehydes or imines, providing a new avenue for rapid assembly of polyfunctionalized boron-containing compounds. We demonstrated that this cascade reaction is highly efficient and compatible with various functional groups, and a wide range of heterocycles. In contrast to a classical Pd(0/II) scenario, mechanistic experiments and DFT calculations have provided strong evidence for a catalytic cycle involving Pd(I)/diboryl carbon radical intermediates.

Chiral Phosphoric Acid-Catalyzed Enantio- and Diastereoselective Allylboration of Aldehydes with β,γ-Substituted Allylboronates

The catalytic asymmetric addition of β,γ-substituted allylboronates to aldehydes has been described. Promoted by 5 mol % chiral phosphoric acid, the reactions were broadly applicable, scalable, and efficient, allowing for the formation of 3,4-anti/syn-homoallylic alcohols bearing adjacent tertiary or quaternary stereogenic centers in a highly enantio- and diastereoselective manner (≤99% ee and dr >20:1). The rigid chairlike transition state involving the chiral phosphoric acid contributed to the highly controlled reaction.

Development of α-Borylmethyl-(Z)-crotylboronate Reagent and Enantioselective Syntheses of (E)-δ-Hydroxymethyl-syn-homoallylic Alcohols via Highly Stereoselective Allylboration.

We report herein the development of α-borylmethyl-(Z)-crotylboronate reagent and the application in highly stereo- and enantioselective syntheses of (E)-δ-hydroxymethyl-syn-homoallylic alcohols. Starting from 1,4-pentadiene, α-borylmethyl-(Z)-crotylboronate was synthesized in two steps with high Z-selectivity and enantioselectivity. Subsequent aldehyde allylboration with the developed boron reagent gave highly enantioenriched (E)-δ-hydroxymethyl-syn-homoallylic alcohols upon oxidative workup.

Regio- and Stereoselective Synthesis of Multi-Alkylated Allylic Boronates through Three-Component Coupling Reactions between Allenes, Alkyl Halides, and a Diboron Reagent.

Multisubstituted allylic boronates are attractive and valuable precursors for the rapid and stereoselective construction of densely substituted carbon skeletons. Herein, we report the first synthetic approach for differentially 2,3,3-trialkyl-substituted allylic boronates that contain a stereodefined tetrasubstituted alkene structure. Copper(I)-catalyzed regio- and stereoselective three-component coupling reactions between gem-dialkylallenes, alkyl halides, and a diboron reagent afforded sterically congested allylic boronates. The allylboration of aldehydes diastereoselectively furnished the corresponding homoallylic alcohols that bear a quaternary carbon. A computational study revealed that the selectivity-determining mechanism was correlated to the coordination of a boryl copper(I) species to the allene substrate as well as the borylcupration step.

Front Cover Picture: Kinetic Resolution of α‐Silyl‐Substituted Allylboronate Esters via Chemo‐ and Stereoselective Allylboration of Aldehydes (9/2021)

Front Cover Picture: Kinetic Resolution of α‐Silyl‐Substituted Allylboronate Esters via Chemo‐ and Stereoselective Allylboration of Aldehydes (9/2021)

Computational Studies of Chiral Hydroxyl Carboxylic Acids: The Allylboration of Aldehydes.

The mechanism of the asymmetric BINOL-derived hydroxyl carboxylic acid catalyzed allylboration of benzaldehyde was investigated using density functional theory calculations. A new reaction model is proposed, and the roles of the two Brønsted acidic sites of the catalyst elucidated. Catalyst distortion was found to be a key factor in determining stereoselectivity. The flexibility of the hydroxyl carboxylic acid catalyst leads to significant differences in the mechanism and origins of selectivity compared to the equivalent phosphoric acid catalyzed reaction.

Kinetic Resolution of α‐Silyl‐Substituted Allylboronate Esters via Chemo‐ and Stereoselective Allylboration of Aldehydes

AbstractWe describe the kinetic resolution of α‐silyl‐substituted allylboronate esters via chiral phosphoric acid‐catalyzed chemo‐, diastereo‐ and enantioselective allylboration of aldehydes. This process provides two synthetically versatile enantioenriched compounds, (Z)‐δ‐silyl‐substituted anti‐homoallylic alcohols and α‐silyl‐substituted allylboronate esters, with a selectivity factor up to 328. We propose that the reaction proceeds through a closed chair‐like transition state with the silane moiety occupying a pseudo‐axial position, thus readily resolving α‐silyl‐substituted allylboronate esters. The synthetic utility of the obtained enantioenriched compounds is highlighted by their further transformations to give a diverse set of enantioenriched molecules.magnified image

Bi(cyclopentyl)diol-Derived Boronates in Highly Enantioselective Chiral Phosphoric Acid-Catalyzed Allylation, Propargylation, and Crotylation of Aldehydes.

In this study, we disclose the catalytic addition of bi(cyclopentyl)diol-derived boronates to aldehydes promoted by chiral phosphoric acids, allowing for the formation of enantioenriched homoallylic, propargylic, and crotylic alcohols (up to >99% enantiomeric excess (ee), diastereomeric ratio (dr) >20:1). These boronate substrates provided superior enantioselectivities, allowing for the reactions to proceed with low catalyst loading (0.5-5 mol %) and reduced reaction time (15 min at room temperature for aldehyde allylboration). A wide substrate scope was exhibited, and the novel boronates provided high enantiocontrol. Reactions with substituted allylboronates and aldehydes yielded vicinal stereogenic alcohols bearing β-tertiary or quaternary carbon centers. High enantio- and diastereoselectivities were found due to the closed six-membered chair-like transition state, with backbone modifications of the boronate and its interactions with the chiral phosphoric acid being the most likely contributing factor.

Nickel-Catalysed Allylboration of Aldehydes

A nickel catalyst for the allylboration of aldehydes is reported, facilitating the preparation of homoallylic alcohols in high diastereoselectivity. The observed diastereoselectivities and NMR experiments suggest that allylation occurs through a well-defined six-membered transition state, with nickel acting as a Lewis acid.

Stereoselective Syntheses of γ,δ-Bifunctionalized Homoallylic Alcohols and Ethers via Chemoselective Allyl Addition to Aldehydes.

Stereoselective synthesis of γ,δ-bifunctionalized homoallylic alcohols and ethers via chemoselective allylation is reported. Pd-catalyzed 1,2-diboration of allenylsilane provided a novel 1,1,2-trifunctional allylation reagent. Allylboration of aldehydes with the reagent followed by in situ protection gave TES-protected homoallylic alcohols with excellent Z-selectivities. Chemoselective allylsilation with the same reagent delivered γ,δ-bifunctionalized homoallylic ethers with high E-selectivities. The bifunctionalized alkene group in the products underwent various transformations without erosion of the olefin geometry.

Preparation of Bifunctional Allylboron Reagent and Application to Aldehyde Allylboration

Synthesis of a bifunctional allylboron reagent via Ni-catalyzed borylation of allylic acetate is reported. Subsequent allylation of aldehydes gave homoallylic alcohols in good yields. The allylsila...

Enantioselective syntheses of (E)-γ,δ-disubstituted homoallylic alcohols via BF3·OEt2-catalyzed aldehyde allylboration and analysis of the origin of E-selectivity: A1,2 allylic strain vs. syn-pentane interaction

Enantioselective allylboration of aldehydes with α-substituted β-methyl allylboronate was reported. By using BF3·OEt2 as the catalyst, γ,δ-disubstituted homoallylic alcohols were obtained in good yields with high E-selectivities and enantioselectivities. Transition state analysis revealed that the disfavored transition state suffers from a syn-pentane interaction between the BF3 catalyst and axially oriented α-substituent of the allylboron reagent. Such a syn-pentane interaction is severe enough to overcome the A1,2 allylic strain between the β-methyl group and the α-substituent of the boron reagent that is present in the favored competing transition state. Consequently, the reaction proceeded with equatorial placement of the α-substituent to furnish γ-methyl substituted homoallylic alcohols with high E-selectivity.

Stereoselective total synthesis of parthenolides indicates target selectivity for tubulin carboxypeptidase activity.

The 2-(silyloxymethyl)allylboration of aldehydes was established to enable stereoselective access to α-(exo)-methylene γ-butyrolactones under mild conditions. Acid-labile functionality and chiral carbonyl compounds are tolerated. Excellent asymmetric induction was observed for β,β'-disubstituted α,β-epoxy aldehydes. These findings led to the enantioselective total synthesis of the sesquiterpene natural product (-)-parthenolide, its unnatural (+)-enantiomer, and diastereoisomers. Among all the isomers tested in cell culture, only (-)-parthenolide showed potent inhibition of microtubule detyrosination in living cells, confirming its exquisite selectivity on tubulin carboxypeptidase activity. On the other hand, the anti-inflammatory activity of the parthenolides was weaker and less selective with regard to compound stereochemistry.

Assembly of Tetrahydropyran Derivatives from Aldehydes, Allylboronates, and Syngas by Asymmetric Relay Catalytic Cascade Reaction.

An efficient synthesis of highly enantio-enriched tetrahydropyrans from readily available aldehydes, allylboronates, and syngas has been established by multiply relay catalysis of rhodium and chiral phosphoric acid. The cascade reaction integrates the asymmetric allylboration of aldehydes and alkene hydroformylation, providing a structurally diverse range of products with different workup procedures. The concise synthesis of key chiral building blocks to access herboxidiene and leucascandrolide A demonstrates the high synthetic utility of this method. The cascade reaction employing alkenes to replace aldehydes was also successful.

Controllable Stereoselective Synthesis of (Z)- and (E)-Homoallylic Alcohols Using a Palladium-Catalyzed Three-Component Reaction.

Diastereoselective synthesis of (Z)- and (E)-homoallylic alcohols using a Pd-catalyzed three-component reaction of 3-(pinacolatoboryl)allyl benzoates, aldehydes, and aryl stannanes was developed, which provides an alternative method for the allylboration of aldehydes using α,γ-diaryl-substituted allylboronates. Both sets of reaction conditions enable access to either (Z)- or (E)-homoallylic alcohols with good to high alkene stereocontrol. The present method showed good functional group compatibility and generality. Efficient chirality transfer reactions to afford enantioenriched (Z)- and (E)-homoallylic alcohols were also achieved.

Enantioselective Allyl-, and Allenylboration of Aldehydes Catalyzed by Chiral Hydroxyl Carboxylic Acid

Asymmetric allylboration of aldehydes with allylboronic acid pinacol ester catalyzed by chiral hydroxyl carboxylic acid is described. This reaction provides synthetically useful homoallyl alcohols in high yield with good to high enantioselectivity. The present catalytic protocol was also examined in asymmetric allenylboration of aldehydes at elevated temperature to afford chiral homopropargyl alcohols with reasonable asymmetric induction.

Allylboration of Aldehydes by Immobilized TRIP

Key words allylboration - homoallylic alcohols - TRIP - immobilization - allylation - aldehydes

Polystyrene-Supported TRIP: A Highly Recyclable Catalyst for Batch and Flow Enantioselective Allylation of Aldehydes

The widely applicable TRIP phosphoric acid catalyst has been immobilized on polystyrene using a copolymerization-based strategy. The resin (PS-TRIP) has proven to be highly active and enantioselective in the asymmetric allylboration of aldehydes. Moreover, it has shown to be extremely robust, as it can be reused for 18 times, after which it still retained its activity. Lastly, to further prove the benefits of the immobilization, a continuous flow experiment spanning 28 h has been carried out with very high yields and ee’s.