Schrock’s tungsten alkylidyne complex 2 to perform RCAM with cyclization
precursor 14 [20, 21] and 16 [22], whereas Fu ¨rstner et al. used Cummins’ trisamidomolybdenum complex 4 for the transformation of 18–19, due to the incompatibility
of the acid-labile OTHP functionality in 18 with complex 2 [23, 24]. Further studies
by Fu ¨rstner et al. in 2010 revealed superbly active catalyst 8 as ideal RCAM
promoter for the generation of alkyne 19, as 8 operates with catalyst loadings as
little as 2 mol% [19]. Complex 12 [24] also performed remarkably well while
needing a significant higher catalyst loading (20 mol%) (Scheme 4).
2.2.2 Lactimidomycin
Considering the substantial increase in strain energy that can be built-up by RCAM,
it is noteworthy to point out that the action of catalyst 8 (5 mol%) on diyne 21
cleanly afforded the desired 12-membered enyne 22 as the sole product, which was
isolated in 95 % (0.6 mmol scale) and 84 % (3.4 mmol scale) yield [25]. These
cyclizations were usually performed at 80
C for 3 h, albeit catalyst 8 per se is fully
operative at ambient temperature. However, the reaction at room temperature
required 24 h to go to completion [19] (Scheme 5).
14,16,18
15,17,19
Scheme 4 Synthesis of cruentaren A, 20 by RCAM strategy
Synthesis of 12- to 16-Membered-Ring Lactones
375
precursor 14 [20, 21] and 16 [22], whereas Fu ¨rstner et al. used Cummins’ trisamidomolybdenum complex 4 for the transformation of 18–19, due to the incompatibility
of the acid-labile OTHP functionality in 18 with complex 2 [23, 24]. Further studies
by Fu ¨rstner et al. in 2010 revealed superbly active catalyst 8 as ideal RCAM
promoter for the generation of alkyne 19, as 8 operates with catalyst loadings as
little as 2 mol% [19]. Complex 12 [24] also performed remarkably well while
needing a significant higher catalyst loading (20 mol%) (Scheme 4).
2.2.2 Lactimidomycin
Considering the substantial increase in strain energy that can be built-up by RCAM,
it is noteworthy to point out that the action of catalyst 8 (5 mol%) on diyne 21
cleanly afforded the desired 12-membered enyne 22 as the sole product, which was
isolated in 95 % (0.6 mmol scale) and 84 % (3.4 mmol scale) yield [25]. These
cyclizations were usually performed at 80
C for 3 h, albeit catalyst 8 per se is fully
operative at ambient temperature. However, the reaction at room temperature
required 24 h to go to completion [19] (Scheme 5).
14,16,18
15,17,19
Scheme 4 Synthesis of cruentaren A, 20 by RCAM strategy
Synthesis of 12- to 16-Membered-Ring Lactones
375