sponges that could find a potential use as an anti-tumor agent, due to its ability to stabilize microtubuli. One of the key steps in the strategy used for the synthesis of the C3-C16 fragment was a chirally catalyzed ene reaction that installed the C15 stereocenter. Treatment of the terminal allyl group of compound 1 with ethyl glyoxylate in the presence of catalytic (S)-BINOL-TiBr2 provided the required alcohol in 74% yield and >95% ds. This method eliminated the need for a protecting group or any other functionality at the end of the molecule. In addition, by carrying out this reaction, Pitts et al. managed to avoid the harsh conditions and low yields associated with installing exo-methylene units late in the synthesis. Chiral C2-symmetric Cu(II) complexes and the synthesis of (+)-azaspiracid-1 Evans and co-workers have devised a new type of enantioselective C2-symmetric Cu(II) catalysts to which substrates can chelate through two carbonyl groups. The catalysts were found to afford high levels of asymmetric induction in several processes, including the ene reaction of ethyl glyoxylate with different unactivated olefins. Figure 15 reveals the three catalysts they found to be the most effective in affording gamma-delta-unsaturated alpha-hydroxy esters in high yields and excellent enantio-selectivities. What is special about compound 2 is that it is bench-stable and can be stored indefinitely, making it convenient to use. The reaction has a wide scope, as shown in Figure 16, owing to the high Lewis acidity of the catalysts, which can activate even weakly nucleophilic olefins, such as 1-hexene and cyclohexene. In the case of catalysts 1 and 2, it has been proposed that asymmetric induction by the catalysts results from the formation of a square-planar catalyst-glyoxylate complex (Figure 17), in which the Re face of the aldehyde is blocked by the tert-butyl substituents, thus allowing incoming olefins to attack only the Si face. This model does not account however for the induction observed when catalyst 3 was employed. The current view is that the geometry of the metal center becomes tetrahedral, such that the sterically shielded face of the aldehyde moiety is the Re face. Initially, the value of the method developed by Evans and coworkers was proved by successfully converting the resulting alpha-hydroxy ester into the corresponding methyl ester, free acid, Weinreb amide and alpha-azido ester, without any racemization, as shown in Figure 18. The azide displacement of the alcohol that results from the carbonyl ene