According to architect James P. Jamieson, as noted in his personal history of the campus Intimate History of Washington University (private press: St. Louis, 1941):

"It will be noted that the axis does not lie due East and West.  Its direction was followed in the orientation of the buildings in Quad 'A' and beyond [original quadrangle with Brookings Hall and Ridgley], but the Chapel, as a 'Chapel' gave an excuse for a change in direction, to give it a true Western front and everything West of it followed suit.  This was done to add interest to the plan, though a more noticeable variation would have been more effective." (pages 5 - 6).

The full text of Jamieson's Intimate History of Washington University http://catalog.wustl.edu:80/record=b3335002~S2 is available to researchers at University Archives.