CYANOKETENES - STEREOCHEMISTRY OF 2-AZETIDINONES RESULTING FROM CYCLOADDITIONS OF CYANOKETENES TO FORMIMIDATES

Tetrahedron Letters No. 11, pp 933 - 936, 1978. CYANOKETENES e STEREOCHEMISTRY FROM THE CYCLOADDITIONS Richard Chambers, DOMa Pergamon Press. Printed in Great Britain. OF THE Z-AZETIDINONES OF CYANOKETENES RESULTING TO FORMIMIDATES Kunert, Louis Hernandez, Jr., Frank Mercer, and Harold W. Moore Department of Chemistry, University of California, (Received in USA 19 November 1977 ; received In the preceding paper’ a synthetic route to chloro-, and 4-protio For those 2-azetidinones containing closely cycloadditions arising from the cycloadditions decoupling techniques, related structural units. data for the P-azetidinones, absorption (C-5) in m was de- as well as some typical alkylcyano- to formimidates to of these adducts to of halocyanoketenes, of the stereo structures. of the individual “C chemical shifts have been made by consideration off-resonance groups reside in a trans relationship. has proven most useful for determination tensities, and iodocyanoketene Reported here are data which show the stereochemistry be that in which the 3-cyano- troscopy bromo-, and methyl), to undergo stereospecific give 2-azetidinones. California in UK for publication 23 January scribed along with the ability of these halocyanoketenes, ketenes (tert-butyl- Irvine, and the comparison cmr spec- The assignments of the relative peak in- of spectra of compounds A summary of the pertinent “C chemical is tabulated in Table 1. shift It is noteworthy that the cyano does not vary by more than 0.3 ppm from 111.6 ppm. tion is consistent with the assumption that these 2-azetidinones This observa- all have the same configura- tion. In view of the invariance of the cyano absorption, of using the “C chemical we chose to investigate the possibility shift of this group as a stereochemical spectra of compounds 3c, 42, 2, 6&, 8a, and 8b were examined. probe. To this end , the “C These compounds were prepared as outlined below and their pertinent &rr data are presented in Table 2. Silica gel chromatography of 2 and% gave samples which were enriched in the E-isomers as determined by the magnitude of the coupling constants of the C-3 and C-4 methine protons in the respective isomers. From these data it is possible to unambiguously assign the up- field cyano resonance to the Zisomer, 112.5 ppm vs 113.1 ppm for 8a. sorptions respective in the E- and Z-iso:ers isomers of 4a and $ I ” respectively, 113.4 ppm vs 113.8 ppm for 2 and It is anticipated that the relative positions of the cyano ab- of ,3x, 2, f%, and 6& should be the same as those for the since a change in the substituent at C-3 (i.e., E-4a *Z-E

In the preceding paper' a synthetic route to chloro-, bromo-, and iodocyanoketene was described along with the ability of these halocyanoketenes, as well as some typical alkylcyanoketenes (tert-butyl-and methyl), to undergo stereospecific cycloadditions to formimidates to give 2-azetidinones. Reported here are data which show the stereochemistry of these adducts to be that in which the 3-cyano-and 4-protio groups reside in a trans relationship.
For those 2-azetidinones arising from the cycloadditions of halocyanoketenes, cmr spectroscopy has proven most useful for determination of the stereo structures. The assignments of the individual "C chemical shifts have been made by consideration of the relative peak intensities, off-resonance decoupling techniques, and the comparison of spectra of compounds containing closely related structural units. A summary of the pertinent "C chemical shift data for the P-azetidinones, 23, is tabulated in Table 1. It is noteworthy that the cyano absorption (C-5) in m does not vary by more than 0.3 ppm from 111.6 ppm. This observation is consistent with the assumption that these 2-azetidinones all have the same configuration.
In view of the invariance of the cyano absorption, we chose to investigate the possibility of using the "C chemical shift of this group as a stereochemical probe. To this end , the "C spectra of compounds 3c, 42, 2, 6&, 8a, and 8b were examined. These compounds were prepared as outlined below and their pertinent &rr data are presented in Table 2.
Silica gel chromatography of 2 and% gave samples which were enriched in the E-isomers as determined by the magnitude of the coupling constants of the C-3 and C-4 methine protons in the respective isomers. 2 From these data it is possible to unambiguously assign the upfield cyano resonance to the Zisomer, respectively, 113.4 ppm vs 113.8 ppm for 2 and 112.5 ppm vs 113.1 ppm for 8a. It is anticipated that the relative positions of the cyano absorptions in the E-and Z-iso:ers of ,3x, 2, f%, and 6& should be the same as those for the respective isomers of 4a and $ since a change in the substituent at C-3 (i.e., E-4a *Z-E I " -  If this is indeed the case, then the E-and Z-isomers of 3c, 6a, 6,b, and 8$ can be assigned on the basis of their C-5 cyan0 absorption as shown in Table 2. This also allows us to assign the E-stereochemistry to the 2-azetidinones, e, based upon the relationship between the C-5 cyan0 absorption of these compounds (Table 1) and the respective cyano absorptions for the Eand Z-isomers of E (Table 2).
As shown in the preceding paper, alkylcyanoketenes (tert-butyl-and methyl-) also add stereospecifically to formimidates. It can now be shown that the resulting P-azetidinones also have stereochemistry analogous to that for 3a-m, &. , 3-alkyl cis to 4-proton.
For example, Irradiation of the C-3 methyl absorption in e and 9b, and the C-3 tert-butyl absorption in g and $J caused a respective increase of 22%, 16%, 22%, and 27% in the integrated intensity of the C-4 methine proton absorption.
Also, as mentioned, ' methylation (CH31) of the anion 2 gives a product identical in all x4espects to 9a. Thus, this alkylation must take place from the side opposite theSCH2(313 group. ThereforeTone can reasonably assume that the major products resulting from halogenation of 5, *. , E-3c, Ez, and E-6b, along with those products arising from the acylation, -aldol condensation, and Michael addition of 5 also have the S-cyan0 and 4-protio groups in a Y traits relationship.
Finally, it is of particular significance to point out that all cyanoketene/formimidate cycloadditions studied give 2-azetidinones having analogous stereochemistry, and that this is completely independent of the steric bulk cf the ketene. Since the observed stereochemistry is counter to that expected if the cycloaddition were a concerted ~2s + v2a reaction, we suggest that these cyanoketene cycloadditions proceed via the zwitterion, l$, and that this undergoes the indicated conrotatory ring closure to the observed 2-azetidinones. The high stereospecificity