Tuning Stereoselection in Tethered Biginelli Condensations. Synthesis of cis- or trans-1-Oxo- and 1-Iminohexahydropyrrolo[1,2-c]pyrimidines

Stereoselection in tethered Biginelli condensations can be tuned to give either the cis or trans stereoisomer of 1-oxohexahydropyrrolo[1,2-c]pyrimidine and 1-iminohexahydropyrrolo[1,2-c]pyrimidine products (see eq 1). With substrates having urea and N-sulfonylguanidine functionality (Schemes 2 and 4), cis stereoselection (4-7:1) is observed when the condensation is accomplished under Knoevenagel conditions, while trans stereoselection (4-20:1) is observed when the condensation is carried out in the presence of polyphosphate ester (PPE). Under both conditions, steroselectivity is highest in the N-sulfonylguanidine series. With substrates bearing a basic guanidine unit, the trans product is formed exclusively under Knoevenagel conditions (Scheme 3).