Without Losing It

Figure 1. The concept from Stoltz et. al. Taken from Ref. [1].

This week sees 2 nice publications for which the synthetic methods concerned have strong potentials as tools in diversity-oriented synthesis (DOS).

The first work, from Prof. Stoltz’s group, pivots on a ring contraction reaction from a 7-membered cycloheptenone to a 5-member acyl-cyclopentenone (Figure 1) [1]. The 7-membered ring precursor is made by a decarboxylative alkylation, catalyzed by Pd(0). An important aspect of the reaction is that a new quaternary, stereogenic carbon center is generated in the process. Asymmetric methods that enable the generations of quaternary carbon centers are highly sought after, and many efforts towards their catalytic versions are also investigated.


Figure 2. The ring contraction. Taken from Ref. [1].

The ring contraction is carried out by LiOH to generate the 5-membered ring (Figure 2). Albeit its simple chemical structure, the 5-membered ring is indeed heavily functionalized and it shows a diverse array of possible reactivities, which is described in Figure 3. A personal observation is that the ‘skipped’ diene should also enable some forms of metal-catalyzed (di)-functionalizations to generate new rings, and the diene also has strong potential to engage in metathesis reaction.


Figure 3. The versatility of the acylcyclopentenone. Taken from Ref.[1].

Stoltz’s results in Figure 3 should convince us that a number of structurally-diverse products can indeed be generated from this common precursor.



Figure 4. The concept of Müller's work. Taken from Ref. [2].

The second work is from Prof. Müller’s group (Figure 4) [2]. They generate a ynedione from a 2-step procedure. Starting with an aromatic heterocycle, they make the intermediate ‘glyoxylyl chloride’ with oxalyl chloride. Then they carry out a Castro- Stephens coupling with Cu(I) catalysis to afford the ynedione (Figure 5). Worthy of note is the contrasting result in a decarboxylative Sonogashira coupling ((which involves a Pd(0) / Cu(I) system), to yield a single-carbonyl ynone instead.


Figure 5. The synthesis of ynedione. Taken from Ref. [2].

The densely functionalized ynedione has the potential to generate a variety of diverse chemical structures, for which a number of them are heterocycles (Figure 6).


Figure 6. The versatility of the ynedione. Taken from Ref. [2].

References:

1. Ring-Contraction Strategy for the Practical, Scalable, Catalytic
Asymmetric Synthesis of Versatile g-Quaternary Acylcyclopentenes.
Allen Y. Hong, Michael R. Krout, Thomas Jensen, Nathan B. Bennett, Andrew M. Harned, and Brian M. Stoltz
Angew. Chemie. Int. Ed.
DOI: 10.1002/anie.201007814

2. Three-Component Synthesis of Ynediones by a Glyoxylation/
Stephens–Castro Coupling Sequence
Eugen Merkul, Janis Dohe, Charlotte Gers, Frank Rominger, and Thomas J. J. M üller
Angew. Chemie. Int. Ed.
DOI: 10.1002/anie.201007194