Asymmetric Synthesis of Diarylmethyl Amines by Rhodium‐Catalyzed Asymmetric Addition of Aryl Titanium Reagents to Imines

Abstract

Asymmetric synthesis of diarylmethyl amines has attracted growing attention owing to their importance in biological activity.[1] Among several methods for performing the asymmetric synthesis, [2,3] catalytic asymmetric addition of aryl metal reagents to imine derivatives seems to be most promising, provided that both high enantioselectivity and high catalytic activity are realized.[4] After our publication on the rhodium-catalyzed asymmetric addition of aryl stannanes to N-sulfonylimines, [5] two reports appeared on catalytic asymmetric arylation: 1) Bräse, Bolm, and co-workers described the addition of a phenylzinc reagent to masked Nformylimines in the presence of a chiral ketimine catalyst, [6] and 2) Tomioka illustrated the rhodium-catalyzed addition of aryl boroxines to N-tosylimines in which high enantioselectivity was observed for sterically tuned aryl imines.[7] Herein we report another rhodium-catalyzed asymmetric arylation in which the addition of aryl titanium reagents to sulfonylimines proceeds with high enantioselectivity under mild conditions (20 8C, 1 h) to give diarylmethyl amines with up to 96 % ee.During our studies on rhodium-catalyzed asymmetric 1,4-additions to a,b-unsaturated ketones, [8] we found that the phenyltitanium reagent PhTi(OiPr) 3 is highly reactive toward transmetalation and forms a phenyl-rhodium bond. In the presence of a rhodium/(S)-binap catalyst in THF at 20 8C, the catalytic 1,4-addition gives titanium enolates as 1,4-addition products with high enantioselectivity.[9] Under similar reaction conditions (Scheme 1), the addition of PhTi(OiPr) 3 [10] (4 a) to N-tosylarylimine 1 a, which was prepared from 4-trifluoromethylbenzaldehyde and 4-toluenesulfonamide, [11] took place rapidly to give the tosylamide of diarylmethyl amine 5 aa after aqueous workup, unfortunately with only 28 % ee (Table 1, entry 1). The use of (S)-H 8 -binap [12] and (S)-segphos [13] in place of (S)-binap [14] improved the enantioselectivity up to 43 % and 76 % ee, respectively (Table 1, entries 4 and 6). The relatively narrow dihedral angle of the biaryl bisphosphine ligand segphos [14] is considered to exert a positive influence on the enantioselectivity in the present

Bis‐Sulfamyl Imines: Potent Substrates for Asymmetric Additions of Arylboroxines under Rhodium Catalysis

“…One key approach to diarylmethylamines is rhodium‐catalysed asymmetric arylation of activated aldimines. The additions of arylstannane,2a aryltitanium,2b arylzinc2c and arylboron reagents3–7 have all been reported with good to excellent enantioselectivities. Arylboron reagents are of particular interest due to their commercial availability, air and moisture stability, low toxicity and functional group tolerance 8.…”

Enantioselective Synthesis of α‐Aryl Alkylamines by Rh‐Catalyzed Addition Reactions of Arylboronic Acids to Aliphatic Imines

“…One of the most attractive approaches for the synthesis of chiral amines is the enantioselective catalytic addition of organometallic reagents to imines 4. Recently, highly enantioselective transition‐metal‐catalyzed additions of organozinc,5 titanium,6 tin,7 and boron reagents8 to aromatic imines have been achieved, with the addition of arylboronic acids being particularly attractive due to the large number and diversity of commercially available derivatives. Despite these considerable advances, catalytic enantioselective addition reactions of aryl boron reagents have been reported only for aromatic imines, thus dramatically limiting the generality of these methods.…”

An N‐Linked Bidentate Phosphoramidite Ligand (N‐Me‐BIPAM) for Rhodium‐Catalyzed Asymmetric Addition of Arylboronic Acids to N‐Sulfonylarylaldimines

“…[1] For achieving a simple access to this versatile skeleton, rhodium-catalyzed enantioselective arylations of imines with arylboron, [2][3][4][5][6][7][8] -zinc, [9] -stannane [10] and -titanium compounds [11] have been developed. Among these extensive studies on catalytic addition of metallic and non-metallic compounds to aldimines, the use of arylboronic acids has attracted much attention due to their low toxicity, compatibility to a broad range of functional groups and high stability in water and air.…”