The Magnificent Six

Figure 1. 3 Numbers, 1 Reaction. (Taken from Ref. [1])

Publications about synthetic concepts are always good, and it is better if their uses can lead to useful, complex structures – a polycyclic system is a good contender. This from group China has demonstrated a nice strategy of making complex , polycyclic scaffolds with Tsuji-Trost style chemistry , catalyzed by Pd(0) catalyst [1]. Figure 1 nicely illustrates how synthons with 3, 4, or 6 carbon atoms can be achieved by Pd(0) catalysis [1]. Worthy of note is the 4-C Synthon scenario. The ‘TMM’ approach has proved to be a classic example for transition metal-catalyzed cycloaddition [2].


Figure 2. Linking 2 rings with a molecular bridge (Path b). (Taken from Ref. [1])

How the researchers use the 6-C synthon for synthesis is nicely shown in Figure 2 [1]. What it really does (path b) is making a fused bicyclic system by creating a ‘chemical link’, rather than stitching 2 rings together (path a).

Thus they allow Compound 3 to react in a double Tsuji-Trost manner to give Comoiund 16 (Figure 3). Compound 16 sets the stage for a double Diels-Alder Reaction with DMAD as the dienophile. The result is the beautiful, symmetric system 17. This double Tsuji-Trost approach should be further developed for synthetic uses.


Figure 3. The symmetric craft - the synthesis of a polycyclic system. (Taken from Ref. [1]).

References:

1. New strategy to construct fused/bridged/spiro carbocyclic scaffolds based on the design of novel 6-C synthon precursor Jia Liu, Xi Wang, Chang-Liang Sun, Bi-Jie Li, Zhang-Jie shi and Min Wang
Org. Biomol. Chem., 2011, Advance Article
DOI: 10.1039/C0OB00660B

2. Some examples:
(a) B. M. Trost and D. M. T. Chan, J. Am. Chem. Soc., 1979, 101, 6429; (b) B. M. Trost, T. N. Nanninga and T. Satoh, J. Am. Chem. Soc., 1985, 107, 721; (c) B. M. Trost and D. T. MacPherson, J. Am. Chem. Soc., 1987, 109, 3483; (d) B. M. Trost, Pure Appl. Chem., 1988, 60, 1615