Interesting question. Assuming the team sheeting Matthews is a rebuilding teams like the Islanders, Coyotes, etc. ... I would take the picks and pay Karlsson. On a team featuring Tavares, Marner, Rielly, Nylander, Kadri, etc., Karlsson is a 75-80 point threat, while Matthews is a 90-100 guy.
That said, if the team sheeting Matthews was a tweener team looking to contend (say Philly), I would try to workout a deal with them first, considering the picks will likely be in the 20s. I'd try to strike a deal with Philly where they get Matthews for Frost, Konecny, Sanheim and a 1st. Then sign Karlsson.
OUT:
Matthews
IN:
Karlsson
Frost
Konecny
Sanheim
1st
I do this because I think Frost will be a Marner (type) player with 70+ point upside. Rielly, Karlsson and Sanheim give the Leafs a very nice BIG 3, and Konecny is the perfect gritty Leaf.