1,3‐Dipolar Cycloadditions of a 2‐Oxoethanenitrile Oxide Derived from (2R)‐Bornane‐10,2‐sultam to Electronically Modified 4,4′‐Disubstituted Stilbenes

Abstract

Thanks to its type-II dipole nature, we were able to demonstrate the higher reactivity of the SO 2 / C¼O syn-conformer for the uncatalyzed 1,3-dipolar cycloaddition of the 2-oxoethanenitrile oxide 2 derived from bornane-10,2-sultam to the symmetric 4,4'-disubstituted trans-stilbenes 3a -3i. The C(a)-si dipolarophile p y approach along the C¼O bond precludes the use of the steric rules formerly expressed for this pseudo-C 2 -symmetric auxiliary. The observed diastereoselectivity is related to the electronic nature of the dipolarophile and may be predicted on the basis of its s para Hammett constant. The absolute configuration was based on the X-ray structure analysis of cycloadduct (4S,5S)-4b, which exhibits an SO 2 / C¼O anti-conformation. Finally, the results obtained with cis-stilbene suggest a nonsynchronous mechanism.Introduction. -Resulting from dipole interactions, N-acyl-substituted (2R)-bornane-10,2-sultam derivatives adopt essentially, in the solid state, the thermodynamically more stable SO 2 /C¼O anti-periplanar conformation 2 ). More than a decade ago, we suggested that the syn-periplanar conformation could lead to a more reactive species in solution, and thus could eventually participate during the course of the reaction by displacing the anti/syn equilibrium 3 ) [8] [9]. This higher reactivity is believed to result from a better electronic alignment between the C¼O moiety and the N lone pair (lp), favoring delocalization on the sultam moiety through a generalized anomeric stabilization of the N lp by the anti-periplanar S¼O s* MO [2]. Indeed, we found that the DhN pyramidal height is directly correlated with the SÀNÀC¼O dihedral angle and reach local and global minima near ca. 170 and À 108, respectively [7] [8]. For syn-periplanar conformations, where the C¼O is bisecting the O¼S¼O angle, the SÀNÀC¼O torsion angle only varies from ca. À 19 to À 98 and the DhN decreases from 0.133 to 0.066 , respectively [7]. Alternatively, in the sterically less constrained anti-conformation, this parameter decreases from ca. 0.40 to 0.11 , for a dihedral angle comprised between ca. 120 and 1708, respectively [7] [8]. This widely

Diastereoselective Alkyl Grignard 1,4‐Additions to para‐Substituted (2R)‐N‐Cinnamoylbornane‐10,2‐sultam Derivatives: Influence of N‐Atom Pyramidalization

“…They rationalized their results on the basis of Oppolzers initial model [9a] but did not discuss the poorer diastereoselectivities observed for sterically more demanding, hence less reactive, Grignard reagents, and, moreover, did not find any electronic correlation. Since we recently demonstrated that the unchelated minor SO 2 /C¼O syn-conformer may, in some instances, be more reactive than its thermodynamically more stable anti-conformer [21] 6 ), the conformational rigidity of the N-alkenoyl side chain is primordial to the N-lp stereoelectronic control, in opposition to the C 2 -symmetrical steric influence, exerted by either the S¼O(2) or C(3) substituents, on the C(a) atom [2], hence, apparently to a much lesser extent, on the C(b) atom. We thus decided to reinvestigate, in more detail, the 1,4addition of the simple ethyl Grignard reagent to p-substituted cinnamoyl derivatives of type 2 7 ), at a conformationally rigidifying and constant low temperature, since such a 2a afforded 3a with 80% d.e.…”

Grignard 1,4‐Additions to para‐Substituted (2R)‐N‐Cinnamoylbornane‐10,2‐sultam Derivatives: Revised Configuration for the N,OAc‐Keteneacetal Formation in the Presence of Cu(I)

“…The initial analytical method was based on the integration of the Me(8) singlet in the 1 H‐NMR analysis of the crude reaction products, as earlier reported in a similar case . Although the sensitivity and precision (±2%), hence the experimental error, of the high‐field NMR method is not fundamentally modified, we now opted for a simple and direct 19 F‐NMR analysis, as earlier reported for this kind of substrates . Indeed, with CFCl 3 as reference, compound p ‐F‐ 2a exhibits two distinct diastereotopic signals at −117.39 (major) and −117.50 ppm (minor), while the p ‐CF 3 O‐ 2b and p ‐CF 3 ‐ 2c analogs exhibit displacements at −58.18/−58.23 and −62.68/−62.73 ppm, respectively.…”

“…We earlier demonstrated that the nonchelated minor SO 2 /C=O syn ‐conformer may, in some instances, be more reactive than its thermodynamically more stable anti ‐conformer , thus following the Acree–Curtin–Hammett principle . Furthermore, the sense of induction may strongly depend on the chelating properties of the reagent and additives, as well as on the conformationally rigidifying low temperature of the reaction…”

Nitrile Oxide, Alkenes, Dipolar Cycloaddition, Isomerization and Metathesis Involved in the Syntheses of 2-Isoxazolines

“…1,3-DP cycloaddition between 2-oxoethanenitrile oxide derived from (2 r )-bornane-10,2-sultam and electronically modified 4,4′-disubstituted stilbenes was analyzed by Romanski, Chapuis, and Jurczak in terms of regioselectivity and mechanism— Scheme 189 [ 200 ].…”