Woodward and Eschenmoser embarked on the project of a chemical synthesis of vitamin B independently from each other. The ETH group started with a model study on how to synthesize a corrin ligand system in December 1959. In August 1961, the Harvard group began attacking the buildup of the B structure directly by aiming at the most complex part of the B molecule, the "western half" that contains the direct junction between rings A and D (the A-D-component). Already in October 1960, the ETH group had commenced the synthesis of a ring-B precursor of vitamin B.
At the beginning, progress at Harvard was rapid, until an unexpected stereochemical course of a central ring formation step interrupted the project. Woodward's recognition of the stereochemical enigma that came to light by the irritating behavior of one of his carefully planned synthetic steps became, according to his own writings, part of the developments that led to the orbital symmetry rules.
After 1965, the Harvard group continued work towards an A-D-component along a modified plan, using (−)-camphor as the source of ring D.