TETRAHEDRON LE'FTERS Pergamon Tetrahedron Letters 40 (1999) 3297-3300 Ring-Closing Metathesis Strategy to P-Heterocycles Paul R. Hanson* and Diana S. Stoianova Department of Chemistry, Universityof Kansas, Lawrence, KS 66045-2506 Received 19 January 1999; revised 23 February 1999; accepted 24 February 1999 Abstract: The first examples ot ring-closing metathesis reactions with allylphosphonamides 1, vinylphosphonamides 2, and vinylphosphonates 8 using the Grubbs ruthenium catalyst 3 are described. These RCM reactions lead to the 6-membered allylphosphonamides 4, the 5-membered vinylphosphonamides 5, and various 5-, 6- and 7-membered phosphonates 9-10. The yield, rate and mode of metathesis in these reactions are sensitive to simple olefin and nitrogen substitution. © 1999 Elsevier ScienceLtd. All rights reserved. The ring-closing metathesis (RCM) 1 reaction continues to emerge as a powerful approach for the construction of complex organic molecules. The Grubbs and Schrock catalysts are the most prevalent catalysts used in organic synthesis. 2 A review has appeared in the literature which thoroughly categorizes the tolerance of both the Schrock and Grubbs catalysts to a vast array of functional groups.3 Recently we have shown that the RCM reaction catalyzed by the Grubbs ruthenium catalyst 3 is an effective method for the construction of cyclic allyl phosphonates (P-heterocycles).4 In the literature, there is only one other example for a RCM reaction on a phosphorus containing compound (phosphine) using the Basset tungsten carbene complex.5 As part of our program aimed at developing organometallic approaches 6 to diverse phosphorus containing compounds, we herein report examples of RCM reactions on diallyl allylphosphonamides 11 diallyl vinylphosphonamides 2 (Scheme 1), and diallyl vinylphosphonates 8 (Scheme 2) using the ruthenium catalyst 3 to derive the P-heterocycles 4-5 and 9-10 (Tables 1-3). Scheme 1 R 2 R 2 m = 1 I O I D R ' ~ N. ~ .. N .,,,,.,,.,,,,.,,.~ R ' Cy3P I~i CI I Ph ol )r. c'°~ u--' 1, 2 cy3P 3 3 m=l,0 " m=O R 2 ~ R 2 I u I R 2 R 2 I O I 5 Phosphorus containing compounds have gained considerable attention due to their diverse biological profiles. 7 One particularly attractive route to phosphonamide and phosphonate heterocycles is via the RCM reaction of allyl and vinylphosphonamides such as 1-2 or vinylphosphonates 8. The syntheses of the starting substrates 1, 2, and 8 are outlined in Scheme 2. Phosphonodichloridate formation from the corresponding allyl or vinylphosphonic acid 8 6 and subsequent treatment with the corresponding amine 9 or alcohol in toluene, 1° produced the desired products in good to modest yields (1 and 8, 52-82%; 2, 32-60%). The results of our RCM studies on allylphosphonamides 1 are shown in Table 1. The RCM reaction of the N-methyl substituted allylphosphonamides lax gave excellent yields of the six membered products 4 a,c.ll The reactions with substrates containing free N-H groups were sluggish and required higher amounts of catalyst, giving moderate yields of the products 4b,d (45-48%). These results are in agreement with the observations of others who have found that cyclization in the presence of a free allylic amide N-H group is problematic.]2 0040-4039/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved. PIL S0040-4039(99)00479-7