Asymmetric addition of arylboroxines to cyclic N-sulfonyl ketimines proceeded in the presence of a rhodium catalyst coordinated with a chiral diene ligand to give high yields of benzosultams, where a triaryl-substituted stereogenic carbon center was created with high enantioselectivity (93-99% ee). The chiral benzosultams were transformed into the chiral (triaryl)methylamines by breaking the cyclic structure.

The transition-metal-catalyzed enantioselective alkylation and arylation of imines is a versatile means of accessing a-chiral amines, which are important structural components of a number of biologically active compounds, and there have been many reports of the successful catalytic enantioselective addition of organometallic reagents to imines derived from aldehydes. [1] In contrast, the asymmetric addition of organometallic reagents to ketimines, which provides chiral a-tertiary amines, remains less developed. [2][3][4] In this context, we have reported that rhodium/chiral diene complexes efficiently catalyze the asymmetric addition of arylboron reagents to N-sulfonyl ketimines with high enantioselectivity. [5,6] Herein, we report the rhodium-catalyzed asymmetric arylation of cyclic N-carbonyl ketimines, which are generated in situ by the dehydration of 3-aryl-3-hydroxyisoindolin-1ones with arylboroxines, resulting in isoindolin-1-ones bearing a triaryl-substituted stereogenic carbon center.The stability of imines towards hydrolysis depends on the substituent on the imine nitrogen. For example, N-sulfonyl imines are sufficiently stable to be isolated and they are often used in the addition of organometallic reagents. On the other hand, when the imines are highly sensitive to hydrolysis, benzotriazole [7] or sulfinic acid imine adducts, [8] or hemiaminals [9b] have been often used as stable imine precursors. We focused on the use of 3-aryl-3-hydroxyisoindolin-1-ones [9] 1 as stable precursors for the generation of cyclic N-carbonyl ketimines bearing a diaryl-substituted azomethine moiety, which can be used in the rhodium-catalyzed asymmetric arylation reaction to produce chiral isoindolin-1-ones, which are structurally important core unit found in many biologically active compounds and natural products (Scheme 1). [10,11] We also decided to use arylboroxines 2, which are dehydrated analogues of arylboronic acids, because they would be expected to work as dehydrating reagents to generate ketimine A, as well as arylating reagents for a subsequent arylation by a rhodium catalyst.It was found that a hydroxorhodium complex was effective in catalyzing the arylation of 3-phenyl-3-hydroxyisoindolin-1-one (1 a) with arylboroxines 2 (Table 1). Thus, treatment of hemiaminal 1 a with p-tolylboroxine (2 m; 2 equiv of B) in the presence of a hydroxorhodium complex [{Rh(OH)(cod)} 2 ] (5 mol % of Rh; cod = 1,5-cyclooctadiene) at 80 8C for 12 h gave 3-phenyl-3-(p-tolyl)isoindolin-1-one (3 am) in 87 % yield (entry 1). The arylating reagent p-tolylboronate 2 m' is also effective, giving 3 am in 85 % Scheme 1. Asymmetric arylation of isoindolin-1-ones 1. Table 1: Rhodium-catalyzed asymmetric arylation of 3-hydroxyisoindolin-1-one 1 a. [a] Entry Catalyst p-tol[B] Yield [%] [b] ee [%] [b] 1 [{Rh(OH)(cod)} 2 ] 2 m 87 -2 [{Rh(OH)(cod)} 2 ] 2 m' 85 -3 [{Rh(OH)(cod)} 2 ] 2 m'' 7 -4 [c] [{RhCl(cod)} 2 ]/KOH (aq) 2 m 0 -5 [d] [{RhCl(cod)} 2 ]/K 3 PO 4 2 m 7 -6 [{Rh(OH)[(R,R)-Bn-tfb*]} 2 ] 2 m 50 33 7 [{Rh(OH)[(R,R)-Ph-tfb*]} 2 ] 2 m 79 87 ...

Asymmetric addition of arylboroxines to δ-aryl-α,β,γ,δ-unsaturated ketones proceeded in the presence of an iridium catalyst coordinated with a chiral diene ligand to give high yields of δ-diaryl ketones with very high enantioselectivity.

The transition-metal-catalyzed enantioselective alkylation and arylation of imines is a versatile means of accessing a-chiral amines, which are important structural components of a number of biologically active compounds, and there have been many reports of the successful catalytic enantioselective addition of organometallic reagents to imines derived from aldehydes. [1] In contrast, the asymmetric addition of organometallic reagents to ketimines, which provides chiral a-tertiary amines, remains less developed. [2][3][4] In this context, we have reported that rhodium/chiral diene complexes efficiently catalyze the asymmetric addition of arylboron reagents to N-sulfonyl ketimines with high enantioselectivity. [5,6] Herein, we report the rhodium-catalyzed asymmetric arylation of cyclic N-carbonyl ketimines, which are generated in situ by the dehydration of 3-aryl-3-hydroxyisoindolin-1ones with arylboroxines, resulting in isoindolin-1-ones bearing a triaryl-substituted stereogenic carbon center.The stability of imines towards hydrolysis depends on the substituent on the imine nitrogen. For example, N-sulfonyl imines are sufficiently stable to be isolated and they are often used in the addition of organometallic reagents. On the other hand, when the imines are highly sensitive to hydrolysis, benzotriazole [7] or sulfinic acid imine adducts, [8] or hemiaminals [9b] have been often used as stable imine precursors. We focused on the use of 3-aryl-3-hydroxyisoindolin-1-ones [9] 1 as stable precursors for the generation of cyclic N-carbonyl ketimines bearing a diaryl-substituted azomethine moiety, which can be used in the rhodium-catalyzed asymmetric arylation reaction to produce chiral isoindolin-1-ones, which are structurally important core unit found in many biologically active compounds and natural products (Scheme 1). [10,11] We also decided to use arylboroxines 2, which are dehydrated analogues of arylboronic acids, because they would be expected to work as dehydrating reagents to generate ketimine A, as well as arylating reagents for a subsequent arylation by a rhodium catalyst.It was found that a hydroxorhodium complex was effective in catalyzing the arylation of 3-phenyl-3-hydroxyisoindolin-1-one (1 a) with arylboroxines 2 (Table 1). Thus, treatment of hemiaminal 1 a with p-tolylboroxine (2 m; 2 equiv of B) in the presence of a hydroxorhodium complex [{Rh(OH)(cod)} 2 ] (5 mol % of Rh; cod = 1,5-cyclooctadiene) at 80 8C for 12 h gave 3-phenyl-3-(p-tolyl)isoindolin-1-one (3 am) in 87 % yield (entry 1). The arylating reagent p-tolylboronate 2 m' is also effective, giving 3 am in 85 % Scheme 1. Asymmetric arylation of isoindolin-1-ones 1. Table 1: Rhodium-catalyzed asymmetric arylation of 3-hydroxyisoindolin-1-one 1 a. [a] Entry Catalyst p-tol[B] Yield [%] [b] ee [%] [b] 1 [{Rh(OH)(cod)} 2 ] 2 m 87 -2 [{Rh(OH)(cod)} 2 ] 2 m' 85 -3 [{Rh(OH)(cod)} 2 ] 2 m'' 7 -4 [c] [{RhCl(cod)} 2 ]/KOH (aq) 2 m 0 -5 [d] [{RhCl(cod)} 2 ]/K 3 PO 4 2 m 7 -6 [{Rh(OH)[(R,R)-Bn-tfb*]} 2 ] 2 m 50 33 7 [{Rh(OH)[(R,R)-Ph-tfb*]} 2 ] 2 m 79 87 ...

syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl glyoxylate and glyoxamide were realized by the use of an axially chiral amino sulfonamide (S)-1. The cross-aldol products obtained are densely functionalized and readily converted to synthetically useful and important chiral building blocks such as γ-lactone and γ-lactam.