Formal anti-Markovnikov hydroamination of terminal olefins

Abstract

A new strategy to access linear amines from terminal olefin precursors is reported. This two-step, one-pot hydroamination methodology employs sequential oxidation and reduction catalytic cycles. The formal hydroamination transformation proceeds with excellent regioselectivity, and only the anti-Markovnikov product is observed. Up to 70% yield can be obtained from styrenes or aliphatic olefins and either primary or secondary aromatic amines. Additionally, the scope is broad with respect to the olefin and accommodates a variety of functionalities; we demonstrate that amines with removable aryl protecting groups may be utilized to allow access to a more diverse array of hydroamination adducts.

Anti-Markovnikov hydroimination of terminal alkynes in gold-catalyzed pyridine construction from ammonia

“…Reaction of 1a with a large excess of NH 3 exclusively afforded 1-phenylethan-1-imine 2e, confirming that the initial step is a Markovnikov hydroamination of alkyne, affording an enamine which may subsequently tautomerize to imine 2e. Next, a 13 C-labeling experiment was conducted with 1a*. When 1a* was employed under the same reaction condition, 5a* was produced which supports the proposed reaction pathway (Fig.…”

“…3 Accordingly, preparation of nitrogen-containing compounds with linear skeleton by direct anti-Markovnikov hydroamination remains highly challenging. 4 Since Beller and co-workers' pioneering work on the first metal-catalyzed anti-Markovnikov hydroamination of olefins in 1999, 5 various methodologies for intermolecular anti-Markovnikov hydroamination with metal catalysts involving alkali metals, 6 alkaline earth metals, 7 organolanthanide, 8 Ti, 9 Re, 10 Ru, 11 Rh, 12 Pd, 13 Cu, 14 Au 15 have been reported to this date. Although such seminal approaches have led to solid progresses, these strategies often involve disadvantages such as limiting the substrate scope, harsh reaction condition, the use of strong bases, or stepwise indirect processes.…”

“…22 Hence, to commence our studies, we designed a novel gold chloride complex supported by a pyrid-2-ylidene ligand L bearing a 1,3,5-trimethylphenyl group and 3,5-di-tertbutylphenyl groups. When the deprotonation of a pyridinium salt [L-H] + [CF 3 SO 3 ] was performed with lithium hexamethyldisilazide (LiHMDS)(3eq), which is followed by the addition of chloro(tetrahydrothiophene)gold(I), a clean reaction occurred with a characteristic signal for the carbene carbon at 187.8 ppm in the 13 C{ 1 H} NMR spectrum. After the products were worked up, LAuCl was obtained as a white solid in 49% yield (Scheme 2).…”

Palladium‐Catalyzed anti‐Markovnikov Oxidation of Terminal Alkenes

“…[43] These reaction conditions were later applied to the preparation of linear amines by a two-step, onepot reductive amination through sequential palladium(II)catalyzed oxidation and iridium(III)-catalyzed reduction. [44] The AM oxidation of allylic alcohols presents opportunities as an alternative to aldol condensations in the synthesis of protected b-hydroxy aldehydes (Scheme 15). Our group reported recently that such regioselectivity could be achieved through the palladium(II)-catalyzed oxidation of ester-protected allylic alcohols using BQ as an oxidant in tertbutanol.…”

Palladium‐katalysierte Anti‐Markownikoff‐Oxidation endständiger Alkene

“…Anschließend berichtete die gleiche Gruppe, dass die Palladium‐katalysierte AM‐Oxidation von Styrolderivaten in Abwesenheit eines Kupfer(II)‐Salzes erreicht wurde und die Beladung des Palladium(II)‐Katalysators von 10 Mol‐% auf 2.5 Mol‐% reduziert werden konnte, wenn die Reaktionen bei 85 °C durchgeführt wurden (Schema ) 43. Diese Reaktionsbedingungen wurden später bei der Herstellung linearer Amine durch eine zweistufige reduktive Eintopf‐Aminierung durch sequenzielle Palladium(II)‐katalysierte Oxidation und Iridium(III)‐katalysierte Reduktion verwendet 44…”