The Weinreb amide method is a good way to prepare ketones in high yields from acid

Chapter 21, Problem 21.6

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The Weinreb amide method is a good way to prepare ketones in high yields from acid chlorides. (a) In the first step of this method, an acid chloride is converted into an amide with N,O-dimethylhydroxylamine. The product is known generically as a Weinreb amide, after its inventor Steven Weinreb (b. 1941), a Pennsylvania State University chemist. Give the structure of the Weinreb amide by completing the following reaction. R MeNH.. OMe Cl C O .. N CHCl3 0 C pyridine N,O-dimethylhydroxylamine (b) The Weinreb amide is allowed to react with a Grignard or organolithium reagent to form a stable tetrahedral addition intermediate. Using a generic structure for the organolithium reagent RLi, draw a structure for this intermediate. This intermediate is stable to decomposition for two reasons. What are they? (Hint: The intermediate contains the metal ion from the Grignard or lithium reagent.) (c) Only after aqueous acid is added does the tetrahedral intermediate break down to the ketone product and other by-products. Write a curved-arrow mechanism for this process and show all the products. (d) Give the products formed when cyclohexanecarbonyl chloride (A) is converted into a Weinreb amide (B), and this amide is allowed to react with propylmagnesium bromide (C) followed by protonolysis. Cl MgBr C O A cyclohexanecarbonyl chloride C propylmagnesium bromide (e) Why not simply allow the acid chloride to react with the Grignard or organolithium reagent? Why is the Weinreb amide used instead?