Cyanoketenes. Cycloadditions of chlorocyanoketene to α,β-unsaturated imines

Abstract Chlorocyanoketene cycloadds to cinnamylideneamines to give β-lactams, δ-lactams, and pyridones. The periselectivity and stereoselectivity of these cycloadditions is markedly influenced by the N-substituent as well as the βsubstituents of the imines.


anticipated
This was, in fact, observed. However, our primary goal was to determine those factors which would maximize the formation of S-lactams of the general structure 1 u' since such compounds would provide reagents for the construction of a large variety of monocyclic S-lactams. 2 For example, reductive dechlorination would give the corresponding 3-cyano-2-azetidinones which are easily functionalized via their enolate anions. 3 Additionally, oxidative cleavage of the alkenyl group would result in a 4-formyl-2-azetidinone and thus allow further modifications via the aldehyde group. 4 The results described here meet the cycloaddition ObJectives, and furthermore, do so in such a fashion as to allow complete control of stereochemistry at positions -3 and -4 DependIn& upon R1 and R 2 exclusively the E-or Z-isomers of Lean be obtained.
A slight excess of CCK (1 1 eq) was generated from the thermolysis of 4-azido-3-chloro-5methoxy-2(2H)-furanone3 in refluxing benzene in the presence of 1 eq of the imines 2a-f I\rc-V.* These imines were chosen so that the steric bulk of both the N-substituent as well as the g-position were systematically varied The observed results are outlined in Scheme 1 The most significant points of this study are the following 1) The selectivity for H-lactam formation is low in the cinnamylideneamine series 2a-c However, formation of the E-isomer z starts to effectively compete as the N-substituent izeduced in steric bulk, 2) Remarkably high selectivity for S-lactam formation is observed for imines 2d,f ,%--,\ Exclusively the Z-isomer, 4d, is formed from the N-tbutyl imine and only the E-isomer 3f results from the N-H-methoxyph?enyl analog The N-cycloheryl -.I imine $, having an intermediately sized N-substituent, gave a mixture of both 8-lactams 3e,4e as -4 well as the b-lactam, 5~ Scheme 1 The structures of the products are based upon spectral (Table l), analytical, and chemical evidence.
The E-stereochemistry for 5a-c was assigned on the basis of their failure to undergo dehydrohalogenation ((C2H5)3N) to thexpective pyridones. The stereochemistry of the B-lactams 3c, 4d, and 3f was assigned on the basis of the following chemical transformations They were Lch*:ehalog:iated (Zn/CH3C02H) and the resulting S-lactams converted to their enolates (NaH/THF).5 Treatment of the enolates from 3&f with N-chlorosuccinimlde regenerated the initial *,/I*+ 3-chloro-2-azetidinones as the major diastereomer.
For the Z-isomer, 4d, Its diastereomer 7 was '2 ,.., the mallor product Thus, assuming that chlorination of the enolates takes place from the least hindered face allows the stereochemical asssignments as indicated for 3c, 4d, and 3f Stereo-I., ?a *-?. chemical assignment of 3e and 4e was made directly from their NMR spectra.
That IS, it has previously been shown that':he prg;on at C 4 in 3-cyano-2-azetidinones experiences a greater deshielding when cis to the 3-cyan0 group than when trans. 6 The assigned stereostructures for 3e and 4e ,, are consistent since the chemical shift of this proton in the former appears at 6, 4.32 and the latter at 6, 4 61 2 NaH 3 NCS 1. Zn/HT 2 NaH

NCS
Detailed mechanistic discussions as well as further synthetic applications will be presented subsequently.
At this time suffice it to say that zwitterions 2 and Aare viewed as the direct precursors to, respectively, 3f and 2 and give such upon conrotatory ring cu closure.