The Pd-catalyzed intramolecular alpha-arylation of amides is applied to the synthesis of functionalized spirooxindoles. The substrate scope is evaluated, and the reaction is demonstrated to be useful for the assembly of spirooxindole natural products and derivatives thereof. As an application, a new synthesis of horsfiline 1 is presented, giving the natural product in only 4 steps from commercially available amino acid 12.

A novel approach to functionalised piperidines is described through a [3+3] cycloaddition reaction of aziridines with Pd-trimethylenemethane complexes. Importantly, the employment of enantiomerically pure aziridines (prepared in three steps from the appropriate amino acids) allows the corresponding piperidines to be furnished in enantiomerically pure form. Additionally, the application of this technique in the total synthesis of (-)-pseudoconhydrine is described.Cycloaddition reactions are amongst the most effective methods for the rapid synthesis of functionalised cyclic systems in a stereocontrolled manner. 1 Additionally, the application of transition metal catalysts in these processes provides added opportunity to exert further control over the efficiency and selectivity of these reactions. In the context of six membered ring formation, the Diels-Alder reaction holds a uniquely prominent position and formally comprises a [4+2] assembly strategy. 2 In contrast, the employment of a [3+3] cycloaddition approach has been much less widely studied. 3 In this context, the employment of Pd-catalysis has led to techniques for the assembly of pyran derivatives 4 whereas piperidine systems have been prepared by a formal [3+3] cycloaddition reaction of 1,3-cyclic sulfates with C,N-dianions, 5 vinylogous amides with a,b-unsaturated iminiums, 6 a,a'-dimethoxylated amides with allyltrimethylsilane 7 and Pd-trimethylenemethane (Pd-TMM) complexes with aziridines. 8 We anticipated that the latter approach represented a potentially efficient technique for the synthesis of enantiomerically pure nitrogen and oxygen containing heterocyclic products through the employment of readily available enantiomerically pure aziridines and epoxides (Figure). Despite the attractiveness of this approach, only a single reaction of this type is known in the literature whereby racemic Ntosyl and N-acyl 2-methylaziridines have been transformed to the corresponding piperidines. 8 We decided to undertake a study of the generality of this [3+3] cycloaddition process, particularly with a view to preparing enantiomerically pure piperidines. Accordingly, we report herein our initial results on the reaction scope and its use in a short enantioselective synthesis of (-)-pseudoconhydrine.Enantiomerically pure aziridines were prepared in 3 steps from the appropriate amino acids by the method of Craig. 9 We decided to employ the commercially available conjunctive reagent 2-[(trimethylsilyl)methyl]-2-propen-1-yl acetate as a convenient source for the in situ generation of the Pd-TMM complex, since it has been applied successfully in the presence of a range of palladium catalysts and has been shown to be an efficient partner for other cycloaddition processes. 10 With the requisite substrates in hand, we began our studies by investigating the effects of catalyst system on the efficiency of the [3+3] cycloaddition reaction. In our hands, the use of Pd(PPh 3 ) 4 following the procedure of Kemmitt et al. 8 was ineffective in promoting piperidine formation. Notably...

A general method to synthesize functionalized azabicyclo[X.3.0]alkane scaffolds 5 is reported. Key intermediates are azabicycloalkenes such as 1 and 2, which are acylated with unsaturated carboxylic acids and subsequently submitted to tandem olefin metathesis. The resulting bicyclic heterocycles are versatile intermediates for different dipeptide mimetics and can be used as intermediates for natural products with indolizidine scaffolds or analogues thereof. [reaction: see text].

This review focuses on recent synthetic developments for the stereoselective preparation of aza-and diazabicyclo[X.Y.0]alkane dipeptide mimetics of the general structures 1-3. Different synthetic strategies are compared with respect to stereoselectivity as well as flexibility regarding ring sizes, stereochemistry and introduction of side-chains.