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In my book it is suggested that in order to add alkyl groups in α,β-unsaturated carbonyl compounds we use organometallic reagents such as organolithium reagents. In the previous chapters it was suggested that the addition of alkyl groups in carbonyl compounds with saturated chains it is conducted by using secondary amines that produce enamines.

I would like to know if it is possible to add alkyl groups in α,β-unsaturated carbonyl compounds by using secondary amines.

enter image description here

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  • $\begingroup$ Where is the alkyl group being added to the unsaturated carbonyl? In a 1,2- or a 1,4-sense? Could you possibly edit your post to include the example from the book (you can upload photographs to imgur using the toolbar when editing) $\endgroup$ – NotEvans. Aug 16 '16 at 20:35
  • $\begingroup$ The addition is 1,2 with organolithium reagents and 1,4 with organocopper reagents. The book is the 6th edition of ''Organic Chemistry" by Vollhardt and Schore. I'm sorry but I am not able to upload a photo. $\endgroup$ – Αντώνιος Κελεσίδης Aug 16 '16 at 20:54
  • $\begingroup$ Do you have a page reference? I have a copy of the book and can upload a picture of the relevant scheme for you $\endgroup$ – NotEvans. Aug 17 '16 at 17:17
  • $\begingroup$ In chapter 18-4 (p. 934 of the Greek edition) the use of secondary amines is presented, while the use of organometallic compounds is presented in chapter 18-10 (p. 950). Thank you very much for your help. $\endgroup$ – Αντώνιος Κελεσίδης Aug 17 '16 at 19:18
  • $\begingroup$ Enamines do not add alkyl groups to carbonyl compounds. They are enolate synthons ($d^2$). Are you confusing this with the Baylis-Hilman reaction? $\endgroup$ – KG3 Jul 27 '18 at 22:38
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If I understand the question correctly (I do not have the book), it goes like this: enter image description here (Ref. J. Am. Chem. Soc. 85, 2, 207-222)

In short I would say that it is not possible to perform the reaction in question in the same way with the Stork enamine alkylation simply because—due to the α,β unsaturation of the ketone—the enamine can not be produced with pyrrolidine. Also, I performed a Reaxys search and found no relevant results. (Of course, I might have missed something.) However, I did find a couple of interesting reactions between cyclohexenone and pyrrolidine which I submit below for completion:

enter image description here

And the following L-Proline organocatalytic reaction taken from: Tetrahedron Letters, 2010, vol. 51, #38, p. 5086 - 5090. Note that compounds 1 and 2 in the scheme were isolated.

enter image description here

However it must be noted that generally, using a different α, β unsaturated ketone and a different amine to the ones used above, the reaction in question is possible as demonstrated by user55119 in his answer here: Why enamine formation does not occur with α,β unsaturated ketones?

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    $\begingroup$ The pyrrolidine enamine of cyclohexanone reaction with methyl vinyl ketone does not stop at the Michael addition product but undergoes an aldol condensation (overall Robinson annulation) to form the pyrrolidine enamine of the enone. This species hydrolyzes with buffered aqueous acetic acid and not with water or aqueous mineral acid. [G. Stork, et al.; pubs.acs.org/doi/pdf/10.1021/ja00885a021] $\endgroup$ – user55119 Jul 28 '18 at 0:35
  • $\begingroup$ @user55119 Well spotted, i have edited it accordingly but did not include all the details so it wont get unnecessary complicated for what the question is asking. Added your reference however so people can take a closer look if needed. Ta! $\endgroup$ – AMM Jul 28 '18 at 6:41
  • $\begingroup$ @AMM Thank you for your response. However, is there no way the last step of the enamine formation mechanism, the deprotonation, occurs at the CH3- side or would such a structure be impossible to exist? $\endgroup$ – Αντώνιος Κελεσίδης Jul 28 '18 at 8:30
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    $\begingroup$ @ΑντώνιοςΚελεσίδης I was thinking the same thing . The only reports of such compounds i found were: Chem. Commun. (London), 1967,0, 862-863 , and Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) (1977), (23), 2571-80; really old articles which i am not sure i trust (for the search i kept the 2,3 and 5,6 unsaturated ring with NA2 on the 1 carbon with A stands for Any atom). Regardless, it is not common and if it does exist it looks like not accessible via the route above. This makes a good question by itself if u like to post, or shall i? $\endgroup$ – AMM Jul 28 '18 at 9:22
  • $\begingroup$ I see. You mean to post a different question regarding the existence of a "diene/amine" structure? If you'd like to, sure. :) $\endgroup$ – Αντώνιος Κελεσίδης Jul 28 '18 at 10:00
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I think that adding alkyl groups to $\alpha$ - $\beta$ unsaturated carbonyl compounds are possible through Enamine synthesis by Secondary amines. But the alkylation will be at the $\alpha$ and $\gamma$ positions as follows.
For simplicity, if we take the corresponding carbonyl compound as Cyclohex-$2$-en-$1$-one, the plausible pathways for alkylation are as follows,
enter image description here

Now, the first step of forming an enamine is already reported. The link for the JACS paper is https://pubs.acs.org/doi/pdf/10.1021/ja061104y .
In this paper, preparation of enamine (by using S-Proline as a secondary amine) of similar kind of $\alpha$ - $\beta$ unsaturated compound has been reported. One of the major reaction in this paper is the following,
enter image description here

Thus it is confirmed that such kind of doubly conjugated enamine formation is possible. The remaining two steps for $\alpha$ - alkylation is also reported earlier. For details, see the paper
https://onlinelibrary.wiley.com/doi/pdf/10.1002/recl.19881070906
Here they have done the following reaction related to this context,
enter image description here

Here $\gamma$ alkylation was disfavoured to preserve the aromaticity of the benzene ring.
But in general, $\gamma$ alkylation forms again a conjugated carbonyl compound, and hence forms the thermodynamically more stable product. So,$\gamma$ -alkylation is more favoured at higher temperature, whereas the $\alpha$ -alkylated product is a kinetic product.
Thus, it is also possible to do alkylation of $\alpha$ - $\beta$ unsaturated compound using a secondary amine, but those alkylation will be specifically in $\alpha$ and $\gamma$ positions (not on $\beta$ positions).

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