Asymmetric Synthesis of 1‑Heteroaryl-1-arylalkyl Tertiary Alcohols and 1‑Pyridyl-1-arylethanes by Lithiation–Borylation Methodology

The synthesis of highly enantioenriched α-heterocyclic tertiary alcohols has been achieved <i>via</i> lithiation–borylation of a configurationally stable lithiated carbamate and heterocyclic pinacol boronic esters followed by oxidation. Protodeboronation of the α-heterocyclic tertiary boronic esters using TBAF·3H₂O or CsF gave highly enantioenriched 1-pyridyl-1-arylethanes in high er

Synthesis of Enantioenriched Tertiary Boronic Esters from Secondary Allylic Carbamates. Application to the Synthesis of C30 Botryococcene

Enantioenriched secondary allylic carbamates have been deprotonated with <i>s</i>BuLi and reacted with boronic esters. In contrast to other electrophiles, high α-selectivity was observed and the boronate complexes were formed with almost complete retention of stereochemistry. The boronate complexes underwent a stereospecific 1,2-migration leading to tertiary allylic boronic esters with high <i>er</i> (>98:2). The scope of the reaction has been explored and found to embrace a broad range of both allylic carbamates and boronic esters. The methodology has been applied to an eight-step, stereoselective synthesis of each of the diastereoisomers of C30 botryococcene

Correction to Synthesis of Enantioenriched Tertiary Boronic Esters from Secondary Allylic Carbamates. Application to the Synthesis of C30 Botryococcene

Correction to Synthesis of Enantioenriched Tertiary Boronic Esters from Secondary Allylic Carbamates. Application to the Synthesis of C30 Botryococcen

Structure and Reactivity of Boron-Ate Complexes Derived from Primary and Secondary Boronic Esters

Boron-ate complexes derived from primary and secondary boronic esters and aryllithiums have been isolated, and the kinetics of their reactions with carbenium ions studied. The second-order rate constants have been used to derive nucleophilicity parameters for the boron-ate complexes, revealing that nucleophilicity increased with (i) electron-donating aromatics on boron, (ii) neopentyl glycol over pinacol boronic esters, and (iii) 12-crown-4 ether

Concise Synthesis of (+)-<i>allo</i>-Kainic Acid <i>via</i> MgI₂‑Mediated Tandem Aziridine Ring Opening–Formal [3 + 2] Cycloaddition

3-Methyl vinyl aziridine undergoes a mild MgI₂-promoted S_N2′ ring opening and concomitant cyclization with fumarate Michael acceptors to give trisubstituted pyrrolidines. The process is efficient and highly diastereoselective. This methodology has been applied to a concise asymmetric synthesis of (+)-<i>allo</i>-kainic acid

Il crudel governo che si fa de’cavalli

Coupling reactions between benzylamines and boronic esters have been investigated. <i>ortho</i>-Lithiated benzylamines react with boronic esters and a <i>N</i>-activator to afford <i>ortho</i>-substituted benzylic boronic esters with formal 1,1′-benzylidene insertion into the C–B bond. The reaction occurs by a S_N2′ elimination and 1,2-metalate rearrangement of the <i>N</i>-activated boronate complex to afford a dearomatized intermediate, which undergoes a Lewis-acid catalyzed 1,3-borotropic shift to afford the boronic ester products in high yield and with excellent enantiospecificity. The use of enantioenriched α-substituted benzylamines gave the corresponding secondary boronic esters with high ee

Synthesis of Enantioenriched Tertiary Boronic Esters by the Lithiation/Borylation of Secondary Alkyl Benzoates

Simple, secondary 2,4,6-triisopropyl benzo­ates (TIB esters) and secondary dialkyl <i>N</i>,<i>N</i>-diisopropyl carbamates have been reported to be resistant to deprotonation by strong bases. We have found that the combination of <i>s</i>BuLi (1.6 equiv) and TMEDA (6 equiv) in CPME at −60 °C enables deprotonation of unactivated secondary dialkyl TIB esters, but not the carbamates. These carbanions were reacted with a range of neopentyl boronic esters which, after 1,2-metalate rearrangement and oxidation, gave a range of tertiary alcohols in high yield and universally high <i>er</i>. Further functional group transformations of the tertiary boronic esters were demonstrated (conversion to quaternary centers, C-tertiary amines) together with application of the methodology to the synthesis of the simplest unbranched hydrocarbon bearing a quaternary center, (<i>R</i>)-4-ethyl-4-methyloctane, validating the synthetic utility of the methodology

Synthesis of Enantioenriched Tertiary Boronic Esters by the Lithiation/Borylation of Secondary Alkyl Benzoates

Simple, secondary 2,4,6-triisopropyl benzo­ates (TIB esters) and secondary dialkyl <i>N</i>,<i>N</i>-diisopropyl carbamates have been reported to be resistant to deprotonation by strong bases. We have found that the combination of <i>s</i>BuLi (1.6 equiv) and TMEDA (6 equiv) in CPME at −60 °C enables deprotonation of unactivated secondary dialkyl TIB esters, but not the carbamates. These carbanions were reacted with a range of neopentyl boronic esters which, after 1,2-metalate rearrangement and oxidation, gave a range of tertiary alcohols in high yield and universally high <i>er</i>. Further functional group transformations of the tertiary boronic esters were demonstrated (conversion to quaternary centers, C-tertiary amines) together with application of the methodology to the synthesis of the simplest unbranched hydrocarbon bearing a quaternary center, (<i>R</i>)-4-ethyl-4-methyloctane, validating the synthetic utility of the methodology

Les rythmes d’apprentissage à l’élémentaire et les « voies » au secondaire

The activation of the S_N2 reaction by π systems is well documented in textbooks. It has been shown previously that this is not primarily due to classical (hyper)­conjugative effects. Instead, π-conjugated substituents enhance favorable substrate–nucleophile electrostatic interactions, with electron-withdrawing groups (EWG) on the sp² system leading to even stronger activation. Herein we report computational and experimental results which show that this activation by sp² EWG-substitution only occurs in a fairly limited number of cases, when the nucleophile involves strong electrostatic interactions (usually strongly basic negatively charged nucleophiles). In other cases, where bond breaking is more advanced than bond making at the transition state, electrophile–nucleophile electrostatic interactions are less important. In such cases, (hyper)­conjugative electronic effects determine the reactivity, and EWG-substitution leads to decreased reactivity. The basicity of the nucleophile as well as solvent effects can help to determine which of these two regimes occurs for a given electrophile

Stereo- and Regiocontrolled Methylboration of Terminal Alkynes

A scalable and operationally simple synthesis of trisubstituted alkenyl boronic esters has been achieved using a Zr-catalyzed carboalumination of terminal alkynes followed by in situ transmetalation with <i>i</i>-PrOBpin. The products are formed in good yields and with excellent regioselectivity and perfect stereoselectivity. The new procedure provides a significant improvement over the previously reported syntheses