The reaction of anhydrous beryllium chloride with nitrogen donors L in diethylether as a solvent under mild conditions affords 1:2 complexes of the type L2BeCl2 [L = benzonitrile (1), pyridine (2), 3,5-dimethylpyridine, pyrrolidine, piperidine (8), and diethylamine (10)]. Structural studies of compounds 1, 2, 8 (CHCl3), and 10 have shown that the complexes have the beryllium centers N2Cl2- tetracoordinated with a distorted tetrahedral geometry of the core unit. In crystals of 8 and 10 these molecules are associated to form helical strings via distinct N-H-Cl hydrogen bonding. The reaction of the weak donor pyrazole (pyz) with (Et2O)2BeCl2 at low temperature gives the mixed complex [(Et2O)(pyz)BeCl2] (4), in which one diethylether molecule is retained in the inner coordination sphere of the metal. In tetrahydrofuran (thf) solution, no reaction is observed with pyrazole, indicating that tetrahydrofuran is the stronger donor as compared to pyrazole, and the (thf)2BeCl2 solvate remains intact. By contrast, with the strong base pyrrolidine (pyrr) the same reaction leads to substitution of one chloride ligand to give the ionic product [(pyrr)3BeCl]+Cl−, (7). Both products (4, 7) have been structurally characterized. At room temperature the reactions with pyrazole or piperidine lead to ether cleavage as a side-reaction which may even become dominant at long reaction times and more forcing conditions. Dinuclear complexes of the type [LBeCl(μ2-OR)]2 are formed, the structures of which have also been determined. The results suggest that hydrogen bonding may assist in the ether cleavage process, since this reaction is not observed for ligands devoid of N-H functions.

Six 4-substituted quinolones 6-8, which bear an ω-iodoalkyl chain, were prepared and subjected to reductive radical cyclisation conditions employing BEt(3)/O(2) as the initiator and either Bu(3)SnH or TMS(3)SiH as hydride source. 4-(4-Iodobutyl)-quinolone (6a) and 4-(3-iodopropylthio)-quinolone (8a) gave the respective 6-endo-cyclisation products in good yields. 4-(3,3-Dimethyl-4-iodobutyl)-quinolone (6b) cyclised in a 5-exo-fashion, while the other substrates delivered only reduction products. The cyclisation reactions could be conducted in the presence of a chiral template (1) with high enantiomeric excess (94-99% ee). The association behaviour of substrate 6a to 1 was studied by NMR titration experiments. In the enantioselective cyclisation of 6b a significant nonlinearity was observed when comparing the product ee with the ee of the template.

The renaissance in radical chemistry during the last years and decades can be explained in large part by the improved prediction and control of the important parameters chemo-, regio-, and stereoselectivity.[1] Recent investigations show that radical reactions can be carried out enantioselectively without an auxiliary being attached covalently to the substrate.[2] Two different strategies have been reported. On the one hand, it is possible to differentiate the enantiotopic faces of a prochiral radical with chiral reagents (reagent control). For this purpose chiral hydrogen-atom donors have been used most often. [3] On the other hand, face differentiation is possible by a Lewis acid, which forms a chelate complex with the substrate, and which is in turn coordinated to chiral ligands.[4] Alternative chiral templates that are based upon noncovalent interactions and are similarly effective have, to the best of our knowledge, not yet been established. In a recent study we were able to show that high enantioselectivity (up to 84 % ee) in radical reactions can be achieved with the help of a hydrogenbonding chiral template. Our preliminary results are presented in this communication.We investigated the enantioselectivity of the reductive radical cyclization of 3-(w-iodoalkylidene)piperidin-2-ones (1). These compounds can be synthesized by the aldol condensation of N-tert-butyloxycarbonyl(Boc)piperidin-2-one with w-tert-butyldimethylsilyl(TBDMS)oxyaldehydes followed by conversion of the protected hydroxy group into an iodo group (1. tetrabutylammonium fluoride (TBAF), THF; 2. PPh 3 , imidazole, I 2 ). [5] In the presence of an initiator and Bu 3 SnH the alkenyl iodides reacted in a 5-or 6-exo-trig-cyclization [1, 6] (e.g. 2 a! 3 a, Scheme 1). The intermediate radicals 3 exhibit a prostereogenic center in a-position to the carbonyl function which is transformed by an intermolecular reaction with Bu 3 SnH to a stereogenic saturated carbon atom. In the case of the alkenyl iodide 1 a both enantiomeric cyclization products 4 a and ent-4 a are formed during the reaction.The reaction proceeded smoothly for the three substrates investigated. The appropriate cyclization products were

[reaction: see text] Enantioselective radical cyclization reactions were performed in the presence of chiral complexing agent 1. The title compounds 3 yielded, depending on the 3'-substitution (R = H, Me), the corresponding endo- (4) or exo-product (5). The highest enantioselectivities (99% and 94% ee) were achieved with 2.5 equiv of complexing agent. The cyclization product trans-4 was obtained in 55% ee in the presence of only 0.1 equiv of complexing agent.

A novel route towards the polyhydroxylated pyrrolizidine alkaloid (+)-alexine has been developed. A key step in this synthesis is a highly stereoselective [3+2] annulation reaction of N-Ts-alpha-amino aldehyde 7 a (Ts=tosyl) and 1,3-bis(silyl)propene 8 a for the construction of the polyhydroxylated pyrrolidine subunit of the target molecule. Previous synthetic strategies rely on carbohydrates that require several protecting-group manipulations, thereby making the total number of steps relatively high. The [3+2] annulation strategy compares favorably with carbohydrate-based syntheses and constitutes a highly efficient entry to polyhydroxylated alkaloids.