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An example of what I mean is here in the synthesis of compound 13. The reaction of the first arrow describes a single reaction, whereas the second arrow to form the final compound seems to have five stages combined into one. I understand that the compound is carried on as is without characterization when the parts are combined into a single step.

If one were designing a new synthesis, what factors would lead one to write (and characterize) each step of the synthesis versus combining many individual reactions in one apparent step?

P. S. This is not an organic chemistry question per se, but meta-ochem (sorry if my tags are limited in description).

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  • $\begingroup$ You seem to be asking about formal rules in the situation where no formal rules exist, nor are they needed. When you design new syntheses, this is the least of your problems. $\endgroup$ – Ivan Neretin Sep 28 '17 at 6:01
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    $\begingroup$ Even a rough set of guidelines, if anyone has ideas, as opposed to "formal rules" would be appreciated. I'm just trying to make sense of this seemingly haphazard notation. $\endgroup$ – halcyon Sep 28 '17 at 6:17
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I want to start off by saying that your example is a particularly bad one. Usually, the arrows in a scheme should at least state a list of reagents and steps. Instead, I would love to discuss this using scheme 7 of Zhang et al.’s Beilstein J. Org. Chem. article.[1] (Beilstein J. Org. Chem. is a open access journal, the full text should be accessible from the DOI link provided below.)

The main reason for combining reactions like this is brevity. For example, every practicing chemist will immediately understand that the homoallyl Grignard under 1. will attack one of the carbonyl functions, that triethylsilane will reduce an oxygen and that TBAF will remove the silyl protecting group on the hydroxy function. None of these steps really warrant any discussion and most people would be able to draw out the missing structures in a few minutes. Likewise, I am not entirely sure why they did not include the preceeding protection into that same reaction scheme because there too there is noting interesting going on.

In more advanced synthetic schemes, the steps that are shortened and written together on a single arrow are often typical name reactions or very easily performed ones:

  • protections and deprotections
  • oxidations of alcohols to aldehydes with standard reagents
  • reductions with DIBAL, LAH or $\ce{NaBH4}$
  • ozonolyses
  • double bond isomerisations
  • simple Wittig/HWE reactions
  • etc.

They are typically chosen in such a way that the path is obvious and that the structure on the end of the arrow can be drawn up quickly by going through the steps. They will practically never include key steps or steps whose stereochemical outcome is uncommon. Cross-couplings of more elaborate structures or lesser known name reactions are also less common.

However, there is no rule as to what can be combined and what cannot. If anything, the reviewers might mark a scheme as too elaborate (i.e. can be shortened) or too brief (needs elaboration).

Reference:

[1]: J. Zhang, H.-K. Zhang, P.-Q. Huang, Beilstein J. Org. Chem. 2013, 9, 2358–2366. DOI: 10.3762/bjoc.9.271.

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