Enantioselective synthesis of chiral 1,2-diamines by the catalytic ring opening of azabenzonorbornadienes: application in the preparation of new chiral ligands

Highly Efficient Rhodium-Catalyzed Asymmetric Ring-Opening Reactions of Oxabenzonorbornadiene with Amine Nucleophiles

“…In general, this type of reaction is highly efficient and characterized with low catalyst loading, high yield and enantioselectivities [1][2][3][4][5][6][7]. Lautens's group has extensively investigated the rhodiumcatalyzed asymmetric ring-opening reactions of oxabenzonorbornadiene with many nucleophiles including alcohols [8,9], phenols [10], amines [11] , carboxylates [12], 1,3-dicarbonyl nucleophiles [13], and sulfur nucleophiles [14] which demonstrated the great promising on providing novel and simple routes to optically active compounds [15][16][17][18]. We herein report a novel extension to Lautens's method, in which the ring of oxabenzonorbornadiene 1a was opened by aliphatic primary amines or substituted N-phenylpiperiazines secondary amines as nucleophiles in the presence of rhodium complex catalyst to afford the corresponding trans-1,2-dihydronaphth-1-ols derivatives with excellent enantioselectivities.…”

Rhodium-Catalyzed Ring-Opening Reactions of N-Boc-azabenzonor­bornadiene with Chiral Amine Nucleophiles Derived from Amino Acids

“…13 We have previously reported the catalytic asymmetric ring-opening reactions of azabenzonorbornadienes with various aliphatic and aromatic amines to give optically active 1,2-diamines with high yield and excellent enantioselectivity. 14, 15 We have subsequently applied this methodology towards the total synthesis of an analgesic compound 14b and the preparation of new chiral ligands. 15 In previous reports, 14a,16,17a high levels of asymmetric induction have been observed, however, the use of large amounts of a tediously prepared chiral ligand 14a,15,18 was required.…”

“…14, 15 We have subsequently applied this methodology towards the total synthesis of an analgesic compound 14b and the preparation of new chiral ligands. 15 In previous reports, 14a,16,17a high levels of asymmetric induction have been observed, however, the use of large amounts of a tediously prepared chiral ligand 14a,15,18 was required. 19 To date, a high yielding, diastereoselective ring-opening of N-Boc-azabenzonorbornadiene (1) with amine nucleophiles containing an a-functional group still remains unexplored.…”

“…Initial conditions with catalytic amounts of Et 3 NHI (20 mol%) were chosen based on our previous reports 15 of the catalytic ring opening of 1 with amine nucleophiles. We found that the addition of the salts could prevent catalyst poisoning, thereby leading to dramatically lower catalyst loading for the efficient ring opening of 1 and decrease equivalents of amine nucleophile as well.…”

“…It is noteworthy that proper selection of the ammonium halide salt for a given reaction is crucial since a dramatic halide effect on the reaction yield and enantioselectivity was noted. 14, 15,17,21 Hydrogen iodide of (S)-proline methyl ester (2a) 22 was prepared and used as the amine nucleophile to optimize the ring-opening reaction of 1. Preliminary screening using 2.0 equivalents of 2a and 3.0 equivalents of i-Pr 2 NEt in the presence of 1.0 mol% of [Rh(cod)Cl] 2 and 3.0 mol% of dppf gave the corresponding ring-opening products 3a and 3a¢ in 42% yield in 1:1.5 ratio ( Table 1, entry 1).…”