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I'm trying to devise a synthesis for the following question.

enter image description here

I am aware it involves retrosynthetic, Wittig, Grignard and diels alder reactions, but unfortunately I can't really grasp all concepts which make me stuck. If there's any help or further explanation would be great.

I have tried to do retrosynthetic for the alkyne compound, also the Wittig reaction. I think Grignard should be the last step where it will change the oxygen bond to $\ce{OH}$. But I can't get myself to there yet.

My attempt

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    $\begingroup$ I would start with the commercially available methyl propiolate and do the D-A on that first $\endgroup$
    – Waylander
    May 21 at 7:16
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Because the target structure contains the motif of a cyclohexane-1,2-diol, I suggest an approach including a Diels-Alder reaction (DA in the illustration below) of 1,3-butadiene and the commercially available diethyl acetal of propargyl aldehyde:

enter image description here

The hydrolysis of the acetal then sets the stage to install the methyl group with the cuprate and 1,4-selectivity in respect to the carbonyl group. As an intermediate protection of the aldehyde, a cyclic acetal is installed. The Prévost reaction typically yields 1,2-(trans)-diols, thus possibly here, too (brief review). Eventually, the deprotected aldehyde is transformed into the exocyclic alkene with the Lombardo reagent. Contrasting to the conditions of a Wittig reaction, the conditions of the Takai-Lombardo reaction are milder (absence of a strong Bronsted base).

Alternative installations of the (trans)-diol could be achieved e.g., by epoxidation and subsequent ring opening with a peracid like mCPBA or (in situ generated by) oxone.

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  • $\begingroup$ This looks good except for the use of propargyl aldehyde which is not commercially available and potentially tricky to handle. A preparation of it is here orgsyn.org/demo.aspx?prep=CV4P0813 $\endgroup$
    – Waylander
    May 21 at 12:14
  • $\begingroup$ @Waylander I agree with your argument. For the purpose of the DA, the dienophil may be an ester (e.g., methyl propiolate). Reduction with LAH, oxidation with TEMPO to generate the aldehyde chemically is possible, but renders overall the reaction lengthy to a total of then eight steps for such a little molecule. If each of them yields the next product by 90%, overall 0.90 ** 8 = 0.43 or 43% over all steps. I anyway redraw it for orthocresol's comment. $\endgroup$
    – Buttonwood
    May 21 at 12:58
  • $\begingroup$ You could use the diethyl acetal of propargyl aldehyde as the dieneophile as it is commercially available. $\endgroup$
    – Waylander
    May 21 at 13:06
  • $\begingroup$ Do you need to reprotect to do the prevost reaction? $\endgroup$
    – Waylander
    May 21 at 19:31
  • $\begingroup$ @Waylander It may be that the reprotection of the aldehyde is not necessary (so far, I never performed a Prévost reaction). On the other hand I consider the dihydroxylation as an oxidation once and because I was once surprised by an aldehyde quickly degrading into an acid I speculated a protection would be a useful safeguard here. The Kürti/Czakó book about name reactions mentions an example (by Deslongchamps et al.) where at least a primary and a secondary alcohol remain intact. Crosslink. $\endgroup$
    – Buttonwood
    May 21 at 20:18

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