Catalytic Enantioselective Intermolecular Benzylic C(sp³)−H Amination

Abstract

A practical general method for asymmetric intermolecular benzylic C(sp3)−H amination has been developed by combining the pentafluorobenzyl sulfamate PfbsNH2 with the chiral rhodium(II) catalyst Rh2(S‐tfptad)4. Various substrates can be used as limiting components and converted to benzylic amines with excellent yields and high levels of enantioselectivity. Additional key features for the reaction are the low catalyst loading and the ability to remove the Pfbs group under mild conditions to give NH‐free benzylic amines.

Dirhodium(II,II) Paddlewheel Complexes

“… Dirhodium(II,II) complexes containing O , O '‐bridging ligands with structural motive OOCCHHetR; Het=nitrogen, R=tertiary substituent: V1 , [230] V2 , [231] V3 , [231] V4 , [239] V5 , [239] V6 , [240] V7 , [241] V8 , [236] V9 , [242] V10 , [243] V11 , [239] V12 , [244] V13 , [245] V14 , [246] V15 , [239] V16 , [227] V17 , [231] V18 , [235] V19 , [247] V20 , [247] V21 , [247] V22 , [229] V23 , [229] V24 , [248] V25 , [249] V26 [248] …”

Site‐Selective Electrochemical Benzylic C−H Amination

“…[1] In this context, C(sp 3 )-H amination has emerged in recently years as an attractive and straightforward approach for forging challenging C À N bonds from readily available materials. [2] Previously reported C-(sp 3 )-H amination reactions usually involve transition metalcatalyzed nitrene insertion [3] or photochemically promoted hydrogen atom transfer (HAT). [4,5] While excellent efficiencies have been observed for benzylic C À H amination employing alkanes as the limiting agent, ample room exists for further development to address site-and chemoselectivities and avoid using stoichiometric oxidants such as hypervalent iodine reagents.…”

“…The prevalence and biological importance of amines has fueled a strong interest in developing more efficient methods for CÀN bond formation. [1] In this context, C(sp 3 )-H amination has emerged in recently years as an attractive and straightforward approach for forging challenging C À N bonds from readily available materials. [2] Previously reported C-(sp 3 )-H amination reactions usually involve transition metalcatalyzed nitrene insertion [3] or photochemically promoted hydrogen atom transfer (HAT).…”

Catalytic Intermolecular C(sp3)–H Amination with Sulfamates for the Asymmetric Synthesis of Amines

“…In this context, we have recently reported the use of benzylic sulfamates in combination with a chiral rhodium(II) complex for the enantioselective benzylic C(sp 3 )-H amination (Scheme 1). 12 We, thus, wish to report in this communication our investigations on the practical features of the reaction. The reagent and the catalyst.…”

“…The reported catalytic asymmetric reaction relies on the combination of the pentafluorobenzyl sulfamate 2 (PfbsNH 2 ) with the chiral complex tetrakis[(S)-(N-tetrafluorophthaloyl)-1-adamantylglycine] dirhodium(II) Rh 2 (S-tfptad) 4 3 in the presence of the commercially available hypervalent iodine reagent PhI(OPiv) 2 . 12 On one hand, the sulfamate is easily accessible from the corresponding alcohol following reaction with sulfamoyl chloride generated in situ from chlorosulfonyl isocyanate in the presence of formic acid. The reaction performed on a 75 mmole scale allows for isolating compound 2 in 85% yield as a white solid (Scheme 2a).…”