Diels–Alder reactivity of trialkyl 2-phosphonoacrylates with N-buta-1,3-dienylsuccinimide

Abstract

N-Buta-1,3-dienylsuccinimide 1 reacts quantitatively with trimethyl 2-phosphonoacrylate 2a to furnish the ortho-[4 ϩ 2]-cycloadduct 3a as a single stereoisomer. The cis axial/equatorial relationship between the succinimido and phosphonate groups respectively has been established by NMR and X-ray diffraction analyses. Triethyl 2-phosphonoacrylate 2b similarly undergoes cycloaddition with the diene 1 to give a 55 : 45 mixture of ortho stereoisomers 3b (cis axial/equatorial) and 4b (trans axial/axial). The activating and directing effect of the phosphonate group is discussed on the basis of a theoretical approach considering the van der Waals complexes.

A Novel Strategy Towards Aminophosphonic Derivatives Based on the Diels-Alder Cycloaddition: Experimental and Theoretical Approaches

“…In the related exo isomer 4 (Scheme 5; X = CH 2 , Y = CO, R = Et and EWG = CO 2 Et) with the phosphonate group in axial position, the 2 J C3-P and 3 J C6-P values were of 0 Hz and 5.4 Hz. The stabilization of the complexes versus the reactant molecules ranged from 7.9 to 10.1 kcal.mol -1 for EWG = CO 2 H and from 4.2 to 5.9 kcal.mol -1 for EWG = CN [29]. The 3 J H3-P constant was also typical of the equatorial/axial position of the phosphonate group as shown in Scheme 7 [30].…”

“…Accordingly, we selected, for our preliminary investigations, stable 1-aminodienes (2) on one hand and trialkyl 2-phosphonoacrylates (1) on the other hand as D-A reaction partners (Scheme 5) [10,[29][30]. Accordingly, we selected, for our preliminary investigations, stable 1-aminodienes (2) on one hand and trialkyl 2-phosphonoacrylates (1) on the other hand as D-A reaction partners (Scheme 5) [10,[29][30].…”

“…The relative configurations of the cycloadducts 3-4 and 6-7 were established by 1 H and 13 C NMR spectroscopy, on the basis of typical H-H, P-H, and P-C coupling constant values [38,[45][46], and in representative cases, on X-ray diffraction analysis of monocrystals [29,45]. For instance, the structure of one endo isomer 3 (Scheme 5; X = CH 2 , Y = CO, R = Me and EWG = CO 2 Me) has been firmly established by X-ray analysis; the succinimidyl and phosphoryl groups are cis to each other, respectively in pseudoaxial and pseudoequatorial positions on the cyclohexene ring which adopts a half-chair conformation.…”

“…The same conformation was observed in solution by NMR analysis (Scheme 7) : two heteronuclear C-P coupling constants appeared to be characteristic of the equatorial position of the phosphonate group, namely the 2 J C3-P and 3 J C6-P values of respectively 5.4 Hz and 12.6 Hz. The stereoselectivity of the cycloadditions of N-1,3butadienyl-succinimide (2, X = CH 2 ; Y = CO) with geminally-substituted vinylphosphonates (Scheme 5; Table 1), leading to a small preference for the endo cycloadducts (3) over the exo isomers (4), has been inspected theoretically considering the relative energies of model cycloadducts [29]. This is in good agreement with calculated values based on the Karplus curve adapted to phosphorus derivatives [46].…”

“…The crude mixture was analysed by NMR, HPLC and GC. The other diastereoisomers were exo-isomer with C3 of (R) configuration (28) and endo isomer with C3 of (S) configuration (29), attributed from NMR analysis of various fractions collected by preparative HPLC. The major isomer 27 was isolated by flash column chromatography on silicagel.…”