Neil Bradley, chief policy officer for the U.S. Chamber of Commerce, said the group has grown increasingly concerned that a fledgling global tax deal may "fundamentally disadvantage U.S. companies."

Bradley's remarks, in an interview Tuesday at Bloomberg News in Washington, cast doubt on Treasury Secretary Janet Yellen's view that U.S. corporate leaders would eventually support the historic deal and urge Congress to pass the legislation necessary to implement it.

There is interest among American companies in the tax agreement's broad goals—especially with regard to the elimination of so-called digital services taxes that many believe unfairly target U.S. firms, Bradley said. But, he added, as Chamber officials dig into the details of the yet-unfinished accord, they're finding more red flags.