How would you carry out the following transformations using an organocopper coupling reaction? M

How would you carry out the following transformations using...

Key Concepts

Multi-step Synthetic Strategy

Often the desired transformation using an organocopper coupling reaction will require multiple steps. This could involve initial functional group manipulations to convert substrates into forms that are more amenable to the coupling reaction, such as preparing a suitable electrophilic partner with an appropriate leaving group. Planning each step carefully, including intermediate formation and purification, is crucial for the successful execution of the overall synthetic route.

Functional Group Interconversion and Leaving Group Activation

Prior to the coupling step, substrates may need to be modified to introduce or improve leaving group ability, enabling efficient nucleophilic substitution. Functional group interconversions, such as halogenation or transformation of alcohols into better leaving groups, are common preparatory steps that make the later organocuprate addition more feasible and selective.

Organocopper Reagents (Gilman Reagents)

Organocopper reagents, often known as Gilman reagents, are organometallic compounds typically prepared by reacting organolithium or organomagnesium reagents with copper(I) salts. These reagents are nucleophilic and are particularly useful for forming carbon–carbon bonds due to their controlled reactivity. They are less reactive than many other organometallic reagents, allowing for greater selectivity in substitution and coupling reactions.

Mechanism of Organocopper Coupling Reactions

The organocopper coupling reaction typically proceeds via an SN2-like mechanism where the nucleophilic organocuprate attacks an electrophilic carbon that carries a good leaving group, such as a halide. This results in the formation of a new carbon–carbon bond. The reaction's stereochemical course and regiochemistry can be influenced by the substrate’s structure, and these nuances must be considered during synthesis planning.

Transcript

00:01 Okay, this problem is asking us to propose the reagents needed for the following transformations, and we are given the fact that we need more than one step in each of these cases.

00:08 So let's zoom into the first one.

00:10 For the first one, we notice that we have a cyclohexene being transformed into a three -methycline.

00:17 So how do we add that methyl group? well, that methyl group, what's special about it is, is that it is added to the allelic position.

00:24 The allelic position is one carbon away from my alkyne.

00:28 So here's my alken.

00:30 One carbon away is my allelic position.

00:34 So how do we add things to the allelic position without affecting the position of the alken? the answer is nbs.

00:40 So nbs will not immediately add a methyl group to that allelic position, but it will add a bromine.

00:48 So the most important thing that nbs does is it adds something without affecting the position of the alken, which is exactly what we want.

00:55 So we still need a methyl group, though.

00:58 And how do we do that? well, if we have a bromine here, that bromine is a good leaving group.

01:03 So it's a good leaving group.

01:04 It can leave, and we can add a carbon -carbon bond, and a gilminary agent will do that.

01:10 So, ch3, 2, copper, lithium.

01:17 So if gilmine reagents are ever confusing, a good way to think about them is, if we have our leaving group, which we do, it will leave.

01:24 Whatever is in the parentheses right here is what will be added in place of my leaving group.

01:28 So, because ch3 is in my parentheses, we are adding that, and that is our product.

01:36 Okay, for the next one, we have an alkyobromide, and we are making some type of alkan.

01:43 So let's see what we're working with.

01:45 So we have 1, 2, 3, 4 carbons, and we need to add 1, 2, 3, 4, 5, 6, 7, 8.

01:54 So we need to add 4 more carbons to make an octane.

01:57 So how do we do this? one potential answer could be just using a gilman reagent.

02:02 So in my previous example, i demonstrated that if we have our leaving group, which we do in this case, we can just add a gryner, sorry, a gilman regent with the corresponding amount of carbons.

02:12 So in this case it would be four carbons, two of them with copper lithium, to make our desired product.

02:18 But remember in our information at the top, it is stated that we need more than one step.

02:23 So we can't just use that gilman regent.

02:25 Instead, we need to make something special, something else.

02:30 I'm going to use lithium.

02:32 I'm going to create my my giumen reagent instead, instead of just using one.

02:38 So that lithium is going to replace my bromine.

02:41 So that is the start.

02:42 I just created an organometallic, which is very similar in reactivity to a granude reagent...

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