Nevertheless, the most important advantages of 8 were the excellent yields
(91 %), the low catalyst loading (2 mol%), and the fact that these reaction can be
run at ambient temperature, albeit 24 h was necessary for the RCAM transformation
to go to completion (Scheme 10).
2.6.2 Latrunculin A
Due to the known incompatibility of complex 4 with N-unprotected amides, the
Teoc derivative 40 allowed RCAM to proceed with high chemoselectivity at the
triple bonds to form the highly strained 16-membered cyclic product 41 in 70 %
yield [35–37]. In this context, it is worth mentioning that standard alkene metathesis
catalysts do not distinguish between alkenes and alkynes, but attack both types of π
systems with similar rates. In summary, this route featured the first successful
implementation of a ring-closing enyne–yne metathesis reaction into a total synthesis of macrocyclic lactones (Scheme 11). Z-Selective hydrogenation of the triple
bond in 41 with Lindlar’s catalyst, in the presence of a large excess of quinoline to
suppress over-reduction, yielded (Z )-alkene 42 in 82 %.
3 Ring-Closing Olefin Metathesis
3.1 Background (RCM)
In ring-closing olefin metatheses (RCM), formally, bond fission of two double
bonds occurs and the new double bond is formed at the same time to produce a
cyclic compound (Scheme 12).
Although RCM has proved to be particularly useful for the synthesis of mediumsized (5–10-membered) rings, this tool was also used for macrocycles exhibiting
ring sizes of 11-membered rings or more. For five- to eight-membered rings
generally thermodynamic (Z)-alkenes were formed, while larger rings were
obtained as E/Z mixtures where the (E)-isomer was dominant. The stereochemical
outcome of the newly formed double bond for 10- to 16-membered rings is a
nontrivial problem since the factors that control the E/Z selectivity still remain
unclear [38].
A large number of catalysts have been developed and employed in RCM over the
past decades [39]. Figure 2 shows only those metal alkylidene complexes that have
been frequently employed in RCM to 12- through 16-membered lactones, namely,
Schrock catalyst 44 and the Grubbs catalysts 45, 46, 47 and 48.
380
M. Cordes and M. Kalesse
(91 %), the low catalyst loading (2 mol%), and the fact that these reaction can be
run at ambient temperature, albeit 24 h was necessary for the RCAM transformation
to go to completion (Scheme 10).
2.6.2 Latrunculin A
Due to the known incompatibility of complex 4 with N-unprotected amides, the
Teoc derivative 40 allowed RCAM to proceed with high chemoselectivity at the
triple bonds to form the highly strained 16-membered cyclic product 41 in 70 %
yield [35–37]. In this context, it is worth mentioning that standard alkene metathesis
catalysts do not distinguish between alkenes and alkynes, but attack both types of π
systems with similar rates. In summary, this route featured the first successful
implementation of a ring-closing enyne–yne metathesis reaction into a total synthesis of macrocyclic lactones (Scheme 11). Z-Selective hydrogenation of the triple
bond in 41 with Lindlar’s catalyst, in the presence of a large excess of quinoline to
suppress over-reduction, yielded (Z )-alkene 42 in 82 %.
3 Ring-Closing Olefin Metathesis
3.1 Background (RCM)
In ring-closing olefin metatheses (RCM), formally, bond fission of two double
bonds occurs and the new double bond is formed at the same time to produce a
cyclic compound (Scheme 12).
Although RCM has proved to be particularly useful for the synthesis of mediumsized (5–10-membered) rings, this tool was also used for macrocycles exhibiting
ring sizes of 11-membered rings or more. For five- to eight-membered rings
generally thermodynamic (Z)-alkenes were formed, while larger rings were
obtained as E/Z mixtures where the (E)-isomer was dominant. The stereochemical
outcome of the newly formed double bond for 10- to 16-membered rings is a
nontrivial problem since the factors that control the E/Z selectivity still remain
unclear [38].
A large number of catalysts have been developed and employed in RCM over the
past decades [39]. Figure 2 shows only those metal alkylidene complexes that have
been frequently employed in RCM to 12- through 16-membered lactones, namely,
Schrock catalyst 44 and the Grubbs catalysts 45, 46, 47 and 48.
380
M. Cordes and M. Kalesse