Reaction of (Z)-1,2-bis(methoxycarbonyloxy)but-2-ene ( 2) of (S)-MeOBIPHEP as the chiral ligand and N,N-bis(ptolylsulfonyl)-o-phenylenediamine (1i) as the nucleophile led with various N,N-bis(arylsulfonyl)-o-phenylenediamines 1 was catalyzed by a palladium complex associated with chiral to the highest ee at 25 °C, regardless of the solvent used. The enantioselectivity of the cyclization is strongly affected by ligands to give optically active 1,4-bis(arylsulfonyl)-1,2,3,4tetrahydro-2-vinylquinoxalines 3 with up to 62% ee. The use the nature of the substituents at the nitrogen atom.
Piperazine derivatives have aroused increasing interest 1c and 1d, the nucleophiles were recovered unchanged after 24 h, even when performing the reaction in DMF. The pres-due to the presence of this heterocyclic skeleton in a large number of therapeutically and biologically active com-ence of a strong base such as DBU gave no more cyclized product. pounds. [1] The synthesis of optically active 2-substituted piperazines has been generally carried out by resolution [2] and only one asymmetric synthesis of (R)-piperazine-2-carboxylic acid has been reported to date. [3] Recently, it was reported by Saegusa and co-workers [4] that 2-butene-1,4diyl dicarboxylates reacted with 1,2-diaminoethanes in the presence of a palladium catalyst to give the piperazine skeleton. This methodology was used by Hayashi et al. [5] and Achiwa et al. [6] to prepare optically active piperazine derivatives with an ee of up to 65% using a palladium complex coordinated with various chiral phosphanes.
In previous papers, we showed the effectiveness of the catalytic synthesis of 2-vinylbenzodioxane [7] and 2-vinylbenzomorpholine [8] by palladium-catalyzed cyclization of Scheme 1. Preparation of 1,2,3,4-tetrahydro-2-vinylquinoxalines catechol or 2-aminophenol with (Z)-1,4-bis(methoxycarbonyloxy)but-2-ene. We wish to report the extension of this cyclization reaction for the construction of chiral 1,2,3,4-Table 1. Palladium-catalyzed synthesis of 1,2,3,4-tetrahydro-2-vi- nylquinoxalines 3 [a] tetrahydro-2-vinylquinoxalines, compounds that are of interest as models for e.g. tetrahydrofolic acid. [9] Entry Substrate 1 Solvent T [°C] Yield of 3 (%) [b] We first focused on the synthesis of racemic 1,2,3,4-tetrahydro-2-vinylquinoxalines. The reaction of various substi-1 a THF 25 0 tuted 1,2-diaminobenzenes (1aϪh) with (Z)-1,4-bis(meth-2 b THF 25 51 3 c THF 50 0 oxycarbonyloxy)but-2-ene (2) was carried out in the pres-4 c DMF 50 0 ence of a palladium complex generated in situ by mixing 5 d THF 50 0 dppb [1,4-bis(diphenylphosphanyl)butane] with Pd 2 (dba) 3 6 d DMF 50 0 7 e THF 25 70 [tris(dibenzylidenacetone)dipalladium]. The results summa-8 f THF 25 50 rized in Table 1 show that the formation of the 1,2,3,4-tetra-9 g THF 25 20 10 h THF 25 58
hydro-2-vinylquinoxaline structure 3 is not observed using o-phenylenediamine (1a), N,N-bis(methylsulfonyl)-o-pheny- [a] All entries carried out under N 2 for 12 h in the presence of lenediamine (1c), or N, N-diacetyl-o-phenylenediamine (1d) palladium catalyst prepared in situ by mixing Pd 2 (dba) 3 (5 mol-% as the nucleophiles (entries 1 and 3Ϫ6). In the case of 1a, Pd) and ligand dppb ([Pd]/[P] ϭ 1:2). The ratio of 1/2 ϭ 1:1.5. Ϫ
[b] Isolated yield after silica gel column chromatography and not the disappearance of the starting material precludes the optimized.
probable formation of polymers, although for compounds
The cyclization reaction was successfully performed using [a] Laboratoire de Synthe `se Asyme ´trique, associe ´au CNRS, CPE the p-tolylsulfonyl and carbamate derivatives 1b, 1e, and 1f,