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In conversation, I just heard:
En cinq ans, il peut s’en passer des choses.
{instead of}: En cinq ans, il peut se passer des choses.
Does "en" refer to "des choses"? Does the version without "en" sound unnatural?
I wonder if the 2nd sentence without "en" can be misinterpreted as another expression "se passer de" in the sense of "do without something"? Which is why the addition of "en" is preferred, to eliminate ambiguity?
This is actually a dislocated construction, but it's missing the comma (which isn't necessarily audible in speech):
Il peut s’en passer, des choses.
Which corresponds to
Des choses, il peut s'en passer.
Where the function of "en" as the pronoun left behind when "des choses" was moved out of the verb phrase becomes perfectly clear.
ETA: A few extra comments on the construction:
The de form is only repeated when the phrase is moved to the beginning of the sentence if it's from a partitive article, not when a preposition, hence
Du lait/de la bière, j'en bois chaque jour (partitive de)
but
La bière, il peut s'en passer (de is a preposition here).
When the preposition and partitive are merged (to avoid a forbidden sequence de des) as in se passer des choses, it's treated as the latter for rules that treated them differently, like in the above example.
Also some phrases with an indefinite article don't seem to dislocate so easily, at least with some verbs:
*un livre, j'en ai besoin (pretty much ungrammatical to me, though maybe others will disagree)
Ce livre, j'en ai besoin (feels kinda awkward, but not outright ungrammatical, the issue may be more with restriction triggered by avoir besoin de)
nor do relatives:
*Je peux m'en passer, de quoi lire. (also wrong)
Does "en" refer to "des choses"?
Yes exactly.
Does the version without "en" sound unnatural?
It does not sounds very natural, but it stills correct. We will naturally add en to insist on the long period.
I wonder if the 2nd sentence without "en" can be misinterpreted as another expression "se passer de" in the sense of "do without something"?
No it cannot because of the context of the sentence, En cinq ans will prevent misunderstanding on il word: il is assumed as indefinite pronoun. It cannot be he, so passer des choses cannot be do without as you mentionned.
