Synthetic Studies on Tricyclic Diterpenoids: Direct Allylic Amination Reaction of Isopimaric Acid Derivatives

Abstract

A selective synthesis of 7- or 14-nitrogen containing tricyclic diterpenoids was completed according to a strategy in which the key step was the catalyzed direct allylic amination of methyl 14α-hydroxy-15,16-dihydroisopimarate with a wide variety of nitrogenated nucleophiles. It was revealed that the selectivity of the reaction depends on the nature of nucleophile. The catalyzed reaction of the mentioned diterpenoid allylic alcohol with 3-nitroaniline, 3-(trifluoromethyl)aniline, and 4-(trifluoromethyl)aniline yield the subsequent 7α-, 7β- and 14αnitrogen-containing diterpenoids. The reaction with 2-nitroaniline, 4-nitro-2-chloroaniline, 4-methoxy-2-nitroaniline, phenylsulfamide, or tert-butyl carbamate proceeds with the formation of 7α-nitrogen-substituted diterpenoids as the main products.

Keywords: allylic amination reaction; diterpenoids; gold catalysis; pimaranes; stereoselectivity.

Figure 1

Substrate scope.

Scheme 1

Amination of methyl 14α‐hydroxy‐15,16‐dihydroisopimarate (2) with 2‐nitroaniline (3). Reagents and conditions: a) catalyst, CH₃CN, rt, 24 h. Catalysts and yields are given in Table 1

Scheme 2

AuCl₃‐catalyzed amination of compound 2 with 4‐nitroaniline (8). Reagents and conditions: a) AuCl₃ (2 mol %), CH3CN, rt, 24 h, 10: 74 %, 11: 19 %.

Scheme 3

Optimization of reaction conditions. Reagents and conditions: a) catalyst, CH₃CN, rt, 24 h. Catalysts, solvents, and yields are given in Table 2

Scheme 4

Reaction of alcohol 2 with anilines catalyzed by AuCl₃−AgOTf. Reagents and conditions: a) AuCl₃–AgOTf, solvent, rt, 24 h; b) AuCl₃−AgOTf, CH₃NO₂, rt, 24 h. Solvents and yields are given in Table 3

Scheme 5

Amination of alcohol 2 with N‐methyl‐4‐nitroaniline (37). Reagents and conditions: a) 2 % AuCl₃−6 % AgOTf, CH₃CN, rt, 24 h, 38: 18 %, 39: 15 %, 5: 31 %, 6: 3 % ; b) 2 % AuCl₃−6 % AgOTf, CH₃NO₂, rt, 24 h, 10/40 (1:1 ratio): 46 %, 5: 38 %.

Scheme 6

Reaction of alcohol 2 with benzenesulfonamide (41). Reagents and conditions: a) 2 % AuCl₃−6 % AgOTf, CH₃CN, rt, 24 h, 42: 41 %, 5/6: 18 % (2:1 ratio).

Scheme 7

Reaction of alcohol 2 with tert‐butyl carbamate (43). Reagents and conditions: a) 2 % AuCl₃−6 % AgOTf, CH₃NO₂, rt, 24 h, 65 %; b) HCl, MeOH, 90 %.

Scheme 8

Transformations of alcohol 2 in the reaction conditions.

Scheme 9

Reaction of alcohol 14 with with 3‐nitroaniline (9). Reagents and conditions: a) 2 % AuCl₃−6 % AgOTf, CH₃CN, rt, 24 h, 12: 51 %, 13: 15 %, 15: 7 %.

Figure 2

Structures of molecules 5, 24, 27, and 36 in the crystals.