Pergamon Tetrahedron Letters, Vol. 38, No. 12, pp. 2065-2066, 1997 O 1997 Elsevier Science Ltd All rights reserved. Printed in Great Britain PII: S0040-4039(97)00286-4 0040-4039/97 $17.00 + 0.00 Ring-Closing Olefin Metathesis for the Synthesis of 1,8-Diazabieyelo[4.3.0]non-3-ene-7,9-diones Alexey B. Dyatkin* Department of Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc. 900 Ridgebury Road, P.O.Box 368, Ridgefield, CT 06877 USA Abstract. A novel method for the efficient synthesis of 1,8-diazabicyclo[4.3.0]non-3-ene-7,9-diones 5 (bicyclic hydantoins) starting from ureas or Z-protected aminoacids has been developed. The key step is a ring-closing metathesis (RCM) reaction of diallyl substituted hydantoins 3 catalyzed by the ruthenium-carbene complex bis(tricyclohexylphosphine)benzilidine ruthenium dichloride (4). © 1997 Elsevier Science Ltd. Grubbs 1 and Schrock 2 have reported the use of efficient catalysts for the metathesis of nonconjugated olefins to form cyclic compounds. The ring-closing metathesis (RCM) reaction has thus become a powerful tool for organic synthesis. This was effectively demonstrated in the synthesis of a variety of carbocycles 3 and heterocyeles 4 and in the total synthesis of natural products. 5 We report herein the application of the commercially available 6 ruthenium carbene complex bis (trieyclohexylphosphine)benzilidine ruthenium dichloride (4) for the synthesis of 1,8-diazabicyelo[4.3.0]non- 3-ene-7,9-diones 5. These compounds have attracted the attention of a number of research groups due to their potential biological application and as templates in organic synthesis; for the preparation of these compounds two major approaches are known. 7, 8 We developed an alternative route to produce 1,8-diazabicyclo[4.3.0]non-3-ene-7,9-diones in moderate to good yields. Starting compounds for this synthesis can be easily prepared by the tandem cyclization- allylation reaction of Z-protected aminoaeids 19 or ureas 210 (Scheme 1). Scheme 1. 0 .... ° t O R 2 ~ ~ O b O. R, 2 a ~....~1~3 ~O N-R1 RI-N.,JI--N-J~OMe H H O 2 ,A.•O L~oN-R1 Reagents and Conditions: a) (i) Nail (4 eq.) (/I} allyl bromide (5 eq.), DMF, 0 °C. b) 4, CH2CI 2, reflux The addition of substrate I or 2 to a suspension of Nail (4 eq.) in dry DMF at 0°C followed by allyl bromide (5 eq.) provided the formation of 1,5-diallylhydantoins 3 in 70-85% yield. Derivatives of glycine (R2= H in 1 and 2) give 1,5,5-triallylated products 3d (R2 = allyl). Intramolecular RCM reactions were performed in refluxing methylene chloride with 10 mol % of 4 as a catalyst, i 1 and in all cases conversion of 3 was more than 95%. Results are presented in the Table 1.12 Surprisingly, compound 3d did not form any spirocyclic product, the lower yield in this case probably can be explained by cross-coupling polymerization. 2065