How can I modify the ozonolysis of cyclohexene such that one of the aldehyde groups of the product, adipaldehyde, is efficiently protected as a base stable protecting group? I know that attempting to monofunctionalize adipaldehyde will lead to mixtures.

My aim is to then do a Wolff–Kishner reduction on the monoprotected dialdehyde.

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    $\begingroup$ Are you trying to make hexanal from cyclohexene? $\endgroup$ – Zhe Jul 17 '18 at 14:48

@Halake: The protection of adipaldehyde as the monoacetal was solved by Schreiber and Claus some years ago [Also see, Schreiber, S.L.; Claus, R.E.; Reagan, J. Tetrahedron Letters, 1982, 23, 3867.] Ozonolysis of cyclohexene (1) in the presence of methanol leads to the molozonide 2, that opens to the zwitterion 3 which is trapped as the methoxy hydroperoxide 4. Addition of p-toluenesulfonic acid catalyzes the formation of the acetal 5. After neutralization with sodium bicarbonate, reduction of the hydroperoxide with dimethyl sulfide affords the monodimethyl acetal of adipaldehyde 6. Since acetals are base stable, Wolff-Kishner reduction of the aldehyde can be accomplished followed by aqueous acid hydrolysis of the acetal.
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I'm assuming you've carried out ozonolysis followed by mild reduction (e.g. using $\ce{Me2S}$) to generate a dialdehyde and now want to convert it to a monoaldehyde. Wolff-Kishner requires basic conditions, so you need a PG insensitive to base. Using ethylene glycol (1 equiv.) in mild acid over a dehydrating agent to generate an acetal would do, but you would need to optimise the conditions to ensure that only one of the aldehyde groups reacts. Then you can carry out Wolff-Kishner as usual and, finally, release the aldehyde in mild acid and excess water.

The question is why would you ever need to do that, if the resulting n-hexanal is readily available from most chemical suppliers?

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    $\begingroup$ This seems like an acceptable method, but will definitely yield a mixture of di-, mono-, and unprotected products. Given that the two aldehyde groups are chemically identical, there really isn't a great way to "ensure" only one of them reacts. $\endgroup$ – ringo Jul 17 '18 at 14:54
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    $\begingroup$ Yes, so you’ll probably need to do several rounds of chromatography and recycling of the di and unprotected products to obtain enough of the mono-acetal. $\endgroup$ – GingerBadger Jul 17 '18 at 14:57
  • $\begingroup$ Very much easier to buy hexan-1-ol and do a Swern. $\endgroup$ – Waylander Jul 17 '18 at 14:58
  • $\begingroup$ Or buy hexanal already ;) $\endgroup$ – GingerBadger Jul 17 '18 at 14:58
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    $\begingroup$ Under the acetal forming conditions you may also get some hemi-acetal formation just to complicate your chromatography further. $\endgroup$ – Waylander Jul 17 '18 at 15:00

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