6‐(Diazomethyl)‐1,3‐bis(methoxymethyl)uracil,Synthesis and Transformation into Annulated Pyrimidinediones |
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Authors: | Fuyi Zhang Anna Kulesza Shikha Rani Bruno Bernet Andrea Vasella |
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Institution: | Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Wolfgang Pauli‐Strasse 10, CH‐8093 Zurich |
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Abstract: | 6‐(Diazomethyl)‐1,3‐bis(methoxymethyl)uracil ( 5 ) was prepared from the known aldehyde 3 by hydrazone formation and oxidation. Thermolysis of 5 and deprotection gave the pyrazolo4,3‐d]pyrimidine‐5,7‐diones 7a and 7b . Rh2(OAc)4 catalyzed the transformation of 5 into to a 2 : 1 (Z)/(E) mixture of 1,2‐diuracilylethenes 9 (67%). Heating (Z)‐ 9 in 12n HCl at 95° led to electrocyclisation, oxidation, and deprotection to afford 73% of the pyrimido5,4‐f]quinazolinetetraone 12 . The Rh2(OAc)4‐catalyzed reaction of 5 with 3,4‐dihydro‐2H‐pyran and 2,3‐dihydrofuran gave endo/exo‐mixtures of the 2‐oxabicyclo4.1.0]heptane 13 (78%) and the 2‐oxabicyclo3.1.0]hexane 15 (86%), Their treatment with AlCl3 or Me2AlCl promoted a vinylcyclopropane–cyclopentene rearrangement, leading to the pyrano‐ and furanocyclopenta1,2‐d]pyrimidinediones 14 (88%) and 16 (51%), respectively. Similarly, the addition product of 5 to 2‐methoxypropene was transformed into the 5‐methylcyclopenta‐pyrimidinedione 18 (55%). The Rh2(OAc)4‐catalyzed reaction of 5 with thiophene gave the exo‐configured 2‐thiabicyclo3.1.0]hexane 19 (69%). The analoguous reaction with furan led to 8‐oxabicyclo3.2.1]oct‐2‐ene 20 (73%), and the reaction with (E)‐2‐styrylfuran yielded a diastereoisomeric mixture of hepta‐1,4,6‐trien‐3‐ones 21 (75%) that was transformed into the (1E,4E,6E)‐configured hepta‐1,4,6‐trien‐3‐one 21 (60%) at ambient temperature. |
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Keywords: | Uracil 6‐(diazomethyl)‐ 2‐Oxabicyclo[4 1 0]heptane 2‐Oxabicyclo[3 1 0]hexane Carbenoids Vinylcyclopropane – cyclopentane rearrangement Pyrimidine‐2 4‐dione Cyclopropane annulated Rhodium catalyst |
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