Fig. 4: Computer-discovered one-pot sequences and MCRs.

For details of mechanistic networks, see Supplementary Figs. S159–S162. a Scheme of a one-pot sequence for the synthesis of branched allyl ethers. The sequence is detected as one-pot rather than the MCR because excessive allyl iodide would react with n-butyllithium, hampering deprotonation and subsequent Wittig rearrangement (cf. Supplementary Fig. S159 marking this conflict). Non-isolated intermediates are shown in brackets and the isolated product 3a is framed in orange. This product has been separately cyclized via ring-closing metathesis to afford cyclic enol ether. Additional derivatives 3b–3d were prepared from allyl iodide and other commercially available β,γ-unsaturated alcohols. b Scheme of a MCR producing unsaturated β-naphthol esters. Key non-isolated intermediates are shown in brackets and the isolated product 4a is framed in orange. Additional derivatives 4b–4e were prepared using different commercially available dienophiles and acylating agents. c Scheme of a MCR producing unsaturated hydroxylated monothio-β-diketones (existing in the thioenol tautomeric form) under basic conditions (top) or 2,3-dihydrothiophenes under acidic conditions (bottom) applied during the last step. Non-isolated intermediates are shown in brackets and the isolated products (5a originally predicted for the top MCR and highest yielding 5b for the bottom one are framed in orange. The monothio-β-diketone product has been separately reacted (dashed arrow) with phenylhydrazine (green) to afford a substituted pyrazole. Additional products 5c–5h were prepared by the top MCR. d Scheme of the MCR producing unsaturated bicyclic lactones. Key non-isolated intermediates are shown in brackets and the isolated product 6a is framed in orange. Additional derivatives 6b–6j were prepared using different commercially available aldehydes and dienes. BHT butylhydroxytoluene, DCB dichlorobenzene, THF tetrahydrofuran, DBU 1,8-diazabicyclo(5.4.0)undec-7-ene, HMPA hexamethylphosphoramide, Pip·OAc piperidinium acetate, dr diastereomeric ratio. Note: 4a was observed as a 1.7:1 mixture of diastereoisomers with two distinct ¹H NMR signals (separated by 0.5 ppm) for Me-OAc protons. These signals can be attributed to known through-space shielding by Ph-N in one of the diastereoisomers. However, no distinct signals allowing for determination of dr’s were observed for structurally similar (OBz vs. OAc) 4d. The product of reverse-demand Diels-Alder cyclization 6g is marked with a star and was isolated as a single diastereoisomer. Percentage values in all panels are isolated yields.