A General Study of [(η⁵‐Cp′)₂Ti(η²‐Me₃SiC₂SiMe₃)]‐Catalyzed Hydroamination of Terminal Alkynes: Regioselective Formation of Markovnikov and Anti‐Markovnikov Products and Mechanistic Explanation (Cp′=C₅H₅, C₅H₄Et, C₅Me₅)

Abstract

A general study of the regioselective hydroamination of terminal alkynes in the presence of [(eta5-Cp)2Ti(eta2-Me3SiC2SiMe3)] (1), [(eta5-CpEt)2Ti(eta2-Me3SiC2SiMe3)] (CpEt=ethylcyclopentadienyl) (2), and [(eta5-Cp*)2Ti(eta2-Me3SiC2SiMe3)] (Cp*=pentamethylcyclopentadienyl) (3) is presented. While aliphatic amines give mainly the anti-Markovnikov products, anilines and aryl hydrazines yield the Markovnikov isomer as main products. Interestingly, using aliphatic amines such as n-butylamine and benzylamine the different catalysts lead to a significant change in the observed regioselectivity. Here, for the first time a highly selective switch from the Markovnikov to the anti-Markovnikov product is observed simply by changing the catalyst. Detailed theoretical calculations for the reaction of propyne with different substituted anilines and tert-butylamine in the presence of [(eta5-C5H5)Ti(=NR)(NHR)] (R=4-C6H4X; X=H, F, Cl, CH3, 2,6-dimethylphenyl) reveal that the experimentally observed regioselectivity is determined by the relative stability of the corresponding pi-complexes 10. While electrostatic stabilization favors the Markovnikov performance for aniline, the steric repulsive destabilization disfavors the Markovnikov performance for tert-butylamine.

Titanium-catalyzed iminohydrazination of alkynes

“…The similar regioselectivities are consistent with an important regiochemical event being associated with a step prior to protonolysis or 1,1-insertion (Scheme 3), e.g., [2 + 2] cycloaddition and/or alkyne coordination. This is in agreement with a recent assertion from the Beller group that titanium hydroamination regioselectivities correlate with calculated relative energies associated with alkyne coordination regioselectivity [23]. However, the experimental protonolysis and 1,1-insertion regioselectivities may or may not be identical, since the gross regioselectivitydetermining events are the same (the [2 + 2] cycloaddition) but other factors still contribute to the final value.…”

Iridium-catalyzed addition of methanol to terminal alkynes

“…Longer reaction time resulted in the formation of other unidentified products. Despite the fact that the titanium-catalyzed synthesis of oct-7-yn-2-one from octa-1,7-diyne has been already reported [17], there has been no evidence on preparation and characterization of 7,7-dimethoxyoct-1-yne so far. The identities of both products were confirmed by means of the NMR spectroscopy.…”

Catalytic Markovnikov and anti‐Markovnikov Functionalization of Alkenes and Alkynes: Recent Developments and Trends

“…Theoretical calculations demonstrated that the observed anti-Markovnikov selectivity is determined by steric interactions of the alkyne with ligands on the titanium center in the corresponding alkyne titanium-pcomplex. [154] Odom and co-workers demonstrated that titanium amido complexes, such as [Ti(NMe 2 ) 4 ] and [Ti(NMe 2 ) 2 (dpma)] (dpma is di(pyrrolyl-a-methyl)-methylamine), are also effective precatalysts for the hydroamination of terminal alkynes, such as 1-hexyne (anti-M:M = 1: > 50), and phenyl acetylene (anti-M:M = 1: > 100) with primary amines to form Markovnikov imines with high regioselectivity. [155] Organolanthanides (e.g.…”