By 1964, the ETH group had accomplished the first corrin model synthesis, and also the preparation of a ring-B precursor as part of a construction of the B molecule itself. Since independent progress of the two groups towards their long-term objective was so clearly complementary, Woodward and Eschenmoser decided in 1965 to join forces and to pursue from then on the project of a B synthesis collaboratively, planning to utilize the ligand construction (ring coupling of components) strategy of the ETH model system.
By 1966, the ETH group had succeeded in synthesizing the B-C-component ("eastern half") by coupling their ring-B precursor to the ring-C precursor. The latter had also been prepared at Harvard from (−)-camphor by a strategy conceived and used earlier by A. Pelter and J. W. Cornforth in 1961. At ETH, the synthesis of the B-C-component involved the implementation of the C,C-condensation reaction via sulfide contraction. This newly developed method turned out to provide a general solution to the problem of constructing the characteristic structural elements of the corrin chromophore, the vinylogous amidine systems bridging the four peripheral rings.
Early in 1967, the Harvard group accomplished the synthesis of the model A-D-component, with the f-side chain undifferentiated, bearing a methyl ester function like all other side chains. From then on, the two groups systematically exchanged samples of their respective halves of the corrinoid target structure. By 1970, they had collaboratively connected Harvards undifferentiated A-D-component with ETHs B-C-component, producing dicyano-cobalt(III)-5,15-bisnor-heptamethyl-cobyrinate 1 (fig. 4). The ETH group identified this totally synthetic corrinoid intermediate by direct comparison with a sample produced from natural vitamin B.
In this advanced model study, reaction conditions for the demanding processes of the C/D-coupling and the A/B-cyclization via sulfide contraction method were established. Those for the C/D-coupling were successfully explored in both laboratories, the superior conditions were those found at Harvard, while the method for the A/B-ring closure via an intramolecular version of the sulfide contraction was developed at ETH. Later it was shown at Harvard that the A/B-ring closure could also be achieved by -iminoester/enamine condensation.
By early 1971, the Harvard group had accomplished the synthesis of the final A-D-component, containing the f-side chain carboxyl function at ring D differentiated from all the carboxyl functions as a nitrile group (as shown in 2 in fig. 4; see also fig. 3). The A/D-part of the B structure incorporates the constitutionally and configurationally most intricate part of the vitamin molecule; its synthesis is regarded as the apotheosis of the Woodwardian art in natural product total synthesis.