Exploiting Carvone To Demonstrate Both Stereocontrol and Regiocontrol: 1,2- vs 1,4-Addition of Grignard Reagents and Organocuprates

Abstract

The ability of certain organometallic reagents to react via 1,2-or 1,4-addition to an α,β-unsaturated ketone is a fundamental example of regioselectivity at the second-year undergraduate organic level. The following two experiments were designed to demonstrate this preference by exploiting carvone as an inexpensive chiral, nonracemic substrate. The first, intended for a typical undergraduate audience, makes use of phenylmagnesium bromide; the second calls for the manufacture of lithium dimethylcuprate from a stock solution of methyl lithium and copper(I) iodide and is envisioned to be carried out by upper-division students. Importantly, due to the chiral nature of carvone, these addition reactions are highly stereoselective and will provide an opportunity for students to revisit stereochemistry. Also discussed are several thoughts on assessment of student learning as well as an easy to adopt protocol that details reaction setup, aqueous workup, purification, waste management, and the analysis of products using 1 H NMR spectroscopy.

Ph2Te2: An Accessible Main Group Organometallic Target for Spectral Characterization and Modeling

“…The importance of organometallic reagents in the inorganic curriculum is supported by the Committee on Professional Training, a recent report providing modules for this field bridging students from the organic sequence to inorganic courses, and numerous recently reported laboratory exercises detailing procedures for the preparation of transition metal-based organometallics. − Despite this, currently there are no reports in this Journal for the preparation of any main group ( s - or p -block) organometallic compounds. Furthermore, there is only one report extant for the synthesis of any tellurium compound (for TeCl 4 in 1946) .…”

(Ph3P)3CuCF3: Preparation and Application of an Air-Stable Trifluoromethylating Agent

“…The importance of organometallic reagents in the inorganic curriculum is supported by the Committee on Professional Training, a recent report providing modules for this field bridging students from the organic sequence to inorganic courses, and numerous recently reported laboratory exercises with elements of transition metal organometallics specifically utilized for organic transformations. − Despite this, currently there is only a single report of a copper-based organometallic reagent in this Journal , in the form of a lithium organocuprate (“Gilman”) reagent . However, no isolation or characterization was carried out as it was not relevant to their procedure.…”

“…16−27 Despite this, currently there is only a single report of a copper-based organometallic reagent in this Journal, in the form of a lithium organocuprate ("Gilman") reagent. 16 However, no isolation or characterization was carried out as it was not relevant to their procedure. Among the prevalent inorganic laboratory textbooks, 28−30 there are no organometallic copper compounds included.…”

Synthesis of Arylpropiolic Acids via Carboxylation of Arylacetylenic Grignard Reagents

“…To the best of our knowledge, no organic chemistry laboratory experiment has been developed that demonstrates the use of Grignard reagents both as a base and as a nucleophile in the synthesis of organic compounds. In fact, a brief survey of the new Grignard reaction laboratory experiments that have been developed recently and published in this journal only show the use of Grignard reagents as nucleophiles. − …”