Comparison Of The Robinson Annulation Reaction

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In 1935, Robert Robinson and his colleague William Sage Rapson published a series of articles for the Journal of the Chemical Society. In them, Robinson and Rapson detail how they performed a number of experiments that synthesized molecules similar in structure to sterols. In particular, Part 7 of their experiments describes what is today known in organic chemistry circles and classrooms alike as the Robinson Annulation Reaction. Figures 1 and 2 above demonstrate two examples of the mechanism for the Robinson Annulation Reaction. In Robinson’s words (1935), this reaction involves a ketone that “might undergo double cyclisation” with formation of a new structure (p. 1533). The Robinson Annulation Reaction constructs a new ring (for example, a six-membered ring) from the original starting ketone found in the reactants. Typically, a structure known as an enolate (the anion formed when an alpha hydrogen in the molecule of an aldehyde or a ketone is removed as a hydrogen ion and contains a double bond because it is resonance stabilized—source: science.uvu.edu) would be added to a methyl vinyl ketone or other enone (compound containing a ketone and an alkene). This process is also known as a base-catalyzed Michael addition. Dehydration, or removal of H2O, then occurs to give a cyclohexenone product.
The article, “Asymmetric one-pot Robinson annulations” (Rajagopal et al., 2001) describes the procedure of a Robinson Annulation Reaction that converts a five-membered cyclic ketone to a two-ring, bicyclic compound. In this reaction, 1.12 g of 0.01 mol dione was added to a solution of 1.15 g of 0.01 mol S-proline in dry DMSO and mixed in a beaker, followed by 0.7 g of 0.01 mol methyl vinyl ketone. This mixture was stirred for 145 ...

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...ucts are in the wrong conformation, the antibiotic will not work affectively in a patient’s system. This is especially useful when there are a set number of starting products, and one wishes to proceed down a chemical pathway in a certain number of steps. This reaction is also utilized as an “environmentally benign approach [to] solvation” (Morrison, et al., 2001) as well as in the production of “complex natural products” in chemical synthesis (Akiyama, et al., 2009). Robinson Annulation is a useful reaction, but not the simplest, so other types of enantioselective synthesis reactions have also been thought up, including “the Lewis acid catalyzed reaction of” regioselective compounds (Huffman, et al., 1985). Lastly, there is a Robinson Annulation Reaction involved in the synthesis of morphine, one of medicine’s basic “pain killer” medications (synarchive.com).

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