Brutal crosswinds repeatedly split the peloton on the 165.5-km stretch from Les Breviaires to Bellegarde and Vuelta a Espana champion Yates lost almost seven minutes.
A crash after 59kms took Spain's Gorka Izagirre out, as well as Warren Barguil, with the Frenchman being taken to a hospital for a scan after losing consciousness.
His Arkea-Samsic team said the 27-year-old, who won the mountain classification in the 2017 Tour de France, suffered a broken neck.
They were only 23 riders left -- including overall contenders Romain Bardet, Nairo Quintana and Bob Jungels -- in the front group some 30kms from the finish line.
A late split meant only seven riders contested the final sprint, Dutchman Groenewegen prevailing again after Sunday's opening win to strengthen his overall lead to 12 seconds.
(Reporting by Julien Pretot; Editing by Ed Osmond)
