Stereoselective Rhodium-Catalyzed Amination of Alkenes

Abstract

The first stereoselective rhodium-catalyzed intermolecular aziridination and C-H amination of alkenes to produce chiral carbamate-protected aziridines and allylic amines is described. Good yields and diastereoselectivities were achieved using a readily available chiral N-tosyloxycarbamate and stoichiometric amount of the alkene substrate. Furthermore the protecting group is easy to cleave under mild reaction conditions.

Simultaneous structure–activity studies and arming of natural products by C–H amination reveal cellular targets of eupalmerin acetate

“…16 Of particular interest to our efforts were inter molecular Rh-catalyzed, C – H amination processes described by the groups of Du Bois, 17,18 Lebel, 19 and others via metallo nitrenoids, 16 which can also deliver aziridines from electron-rich olefins with certain catalysts. 20,21 We envisioned that the application of C – H aminations using a metal nitrenoid precursor bearing an alkyne to derivatize native, bioactive natural products would enable simultaneous arming and SAR studies of natural products at ‘unfunctionalized’ positions. The attached alkyne enables subsequent conjugation to various tags ( e.g.…”

2.9 C—N Bond Formation by C—H Functionalization via Metal-Catalyzed Nitrene Insertion

“…As a more accessable alternative, N-(mesyloxy)and N-(tosyloxy)carbamates 46 can be used as precursors for generating metal nitrenes, without addition of an extra oxidant (Scheme 14). [29,30] The chiral aminating reagents 46 may be prepared from (R)-2,2,2-trichloro-1-phenylethanol, available from facile catalytic asymmetric reduction. Following amination upon exposure to Rh 2 {(S)-Br-nttl} 4 (45), the alcohol is recoverable via carbamate exchange.…”

“…Scheme 14 Intermolecular Stereoselective Amination with N-Oxidized Carbamates [29,30] 2-naphthyl OMs KOAc EtOAc >99:1 73 [30] 4-TolCH=CH OTs K 2 CO 3 PhCF 3 11:1 58 [29] 2-ClC 6 H 4 CH=CH OTs K 2 CO 3 PhCF 3 >50:1 43 [29] 4-MeOC 6 H 4 C"C OMs KOAc EtOAc >99:1 50 [30] a dr of product after purification. (R)-2,2,2-Trichloro-1-phenylethyl [(R,E)-4-(4-Tolyl)but-3-en-2-yl]carbamate (47, R 1 = 4-TolCH=CH); Typical Procedure: [29] To a soln of (R)-2,2,2-trichloro-1-phenylethyl N-(tosyloxy)carbamate (46, R 2 = OTs; 132 mg, 0.300 mmol) in PhCF 3 (1.0 mL) was added Rh 2 {(S)-Br-nttl} 4 (45; 22 mg, 5 mol%) and (E)-4-(but-1-enyl)toluene (36.6 mg, 0.25 mmol).…”

“…(R)-2,2,2-Trichloro-1-phenylethyl [(R,E)-4-(4-Tolyl)but-3-en-2-yl]carbamate (47, R 1 = 4-TolCH=CH); Typical Procedure: [29] To a soln of (R)-2,2,2-trichloro-1-phenylethyl N-(tosyloxy)carbamate (46, R 2 = OTs; 132 mg, 0.300 mmol) in PhCF 3 (1.0 mL) was added Rh 2 {(S)-Br-nttl} 4 (45; 22 mg, 5 mol%) and (E)-4-(but-1-enyl)toluene (36.6 mg, 0.25 mmol). The mixture was stirred for 5 min and sat.…”

Chemo‐ and Enantioselective Intramolecular Silver‐Catalyzed Aziridinations

“…Asymmetric,metal-catalyzed nitrogen-atom-transferr eactions offer excellent opportunities to transform simple precursors into enantioenriched amines,k ey building blocks for pharmaceuticals,a grochemicals,n atural products,a nd ligands. [1,2] Additions of metal nitrenes to alkenes are particularly useful, as the strain in the resulting aziridines enables facile nucleophilic ring cleavage to furnish enantioenriched amines,a mino acids,a minoalcohols,a nd b-lactams. [3] Compared to asymmetric epoxidations,t he corresponding aziridinations are underexplored and display narrower substrate scope.Herein we report an intramolecular chemo-and enantioselective silver-catalyzed nitrene transfer which furnishes di-and trisubstituted aziridines in good yields and ee values.Ring opening with diverse nucleophiles occurs at the distal aziridine carbon atom to yield amines with excellent retention of stereochemical information.…”