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The fundamental structure of a typical mainstream two-semester organic chemistry course, populated mostly by life science majors and taught at universities throughout the United States, has changed little since the 1970s. However, much of the research on learning in organic chemistry has been devoted to characterizing student difficulties of various types, and there is now persuasive evidence that organic chemistry as currently taught is neither effective nor relevant for a majority of students. In an attempt to address the problems with traditional approaches to organic chemistry instruction, we have developed an approach to the design of a transformed organic chemistry course (Organic Chemistry, Life, the Universe and Everything or OCLUE) suitable for the vast majority of organic chemistry students that includes (1) using the Framework of three-dimensional learning (3DL) to support knowledge in use and (2) emphasizing biologically important mechanisms. In this course, topics are connected to core ideas ...