دانلود رایگان مقاله سنتز کاتالیزور گوانیدین کایرال جدید و کاربرد آن در واکنش پیکتت-اسپنگلر نامتقارن

1. Introduction

Guanidine containing compounds have been used in various organic reactions as strong organic bases. Various chiral guanidine derivatives comprising from acyclic to polycyclic systems have been reported in the literature and have been used in a variety of asymmetric reactions e.g., Michael, Henry, Mannich, Strecker [1]. They activate the substrates by unique mode of dual hydrogen bonding thus providing high catalytic as well as high enantioselective activities. Several effective organocatalysts possessing the guanidinium functional group have been introduced to organic synthetic methodology. For example, chiral guanidine based on (R)-(+)-1-phenylethylamine was first developed by Nájera as the catalyst for asymmetric addition of nitroalkanes to aldehydes [2]. In the following years, many other scaffolds were introduced as effective and enantioselective chiral guanidine catalysts. These include Lipton's dipeptide guanidine [3] and Corey's bicyclic guanidine [4], useful for asymmetric Strecker reaction. Selected other chiral guanidine catalysts like Ishikawa's bifunctional guanidine [5,6], Terada's binaphthyl-based guanidine [7–9], and Tan's modified Corey-type bicyclic guanidine [10–15]. Finally, Dixon has developed a class of chiral bifunctional thiourea imininophosphoranes as effective catalysts for asymmetric nitro-Mannich reaction [16]. Also recently, Wang introduced a very effective tartrate-derived guanidine for diastereoselective Michael addition of 3-subtituted oxindoles to nitroolefins [17]. The introduction of an electron-withdrawing group attached to the guanidine moiety increases the acidity of the N\\H bonds thus allowing the construction of new effective organocatalysts acting as strong hydrogen bond donors [18].

3. Results and discussion

The construction of chiral guanidine catalyst 5 is depicted in Scheme 1. The synthesis started with the transformation of (R)-(+)-1-phenylethylamine 1 into its hydrochloride salt 2 which was then treated with cyanamide (NH2CN) at pH 8–9 in water under reflux to afford guanidine hydrochloride [19] which was subsequently converted into the free guanidine 3 by passing through Amberlite IRA-401 column (hydroxide form). Guanidine 3 was then reacted with 2,3-diphenylcycloprop-2- enone 4 in benzene:EtOH (1:1) at room temperature affording compound 5 in 55% yield as a single diastereomer in the form of crystalline solid. Other stereoisomer was not detected. As indicated in the 1 H NMR spectrum, phenyl substituents at dihydropyrimidinone ring were in trans disposition to each other having the value of the coupling constant of the adjacent methine protons of 9.0 Hz. The structure and stereochemistry of compound 5 was unambiguously established by X-ray analysis (Fig. 1). To verify the effectiveness of the newly synthesized guanidine catalysts 5, we first employed it in the Pictet-Spengler reaction [22] of protected tryptamine 6a and p-bromobenzaldehyde 7a in dichloromethane (Table 1). The cyclized product 8a was formed in 28% yield and with 13% ee (Entry 1). Further, we checked the catalytic activity of 5 in different solvents. In less polar solvents (e.g. benzene, toluene and xylene) (Entry 2–4) it gave the product in 8–15% yield and 2–8% ee, while the reaction in CHCl3 (Entry 5) gave 15% yield and 9% ee. In polar solvents, like THF (Entry 6), it gave similar chemical yield (17%) of the product with 17% ee. When the reaction was carried out in protic solvents (like MeOH, i-PrOH) (Entry 7, 8), the product was not detected. We then assumed THF as the best solvent for further optimization.