Comparative Infrared, Raman, and Natural‐Bond‐Orbital Analyses of King's Sultam

Abstract

Dedicated to Dr. G¸nther Ohloff on the occasion of his 80th anniversary By means of 1 H-NOESY-and Raman-spectroscopic analyses, we experimentally demonstrated the presence of the equatorial NÀMe conformer of King×s sultam 4b in solution, resulting from a rapid equilibrium. As a consequence, the value of the N lone-pair anomeric stabilization should be revised to 1.5 ± 1.6 kcal/mol. Independently from the N tilting, natural bond orbital (NBO)-comparative analyses suggest that the S d* orbitals do not appear as primordial and stereospecific acceptors for the N lone pair. Second, the fivemembered-ring sultams do not seem to be particularly well-stabilized by the SÀC s* orbital in the N-substituted pseudo-axial conformation, as opposed to an idealized anti-periplanar situation for the six-membered-ring analogues. In this latter case, the other anti-periplanar CÀC s* and C(1')ÀH/C(2') s*orbitals are as important, if not more, when compared to the SÀC s* participation. In the pseudo-equatorial conformation, g-sultams particularly benefit from the N lone-pair hyperconjugation with the anti-periplanar SÀO 1 s* and C(2)ÀH/C or C(1')ÀH/C s* orbitals. This is also the case for d-sultams when the steric requirement of the N-substituent exceeds 1.6 kcal/mol. When both axial and equatorial conformations are sterically too exacting, the N-atom is prone to sp 2 hybridization or/and conformational changes (i.e., 12c). In that case also, the mode of stereoelectronic stabilization differs from g-to d-sultams.Introduction. ± Based on semi-empirical calculations, we proposed in [1] that the steric origin of the diastereoselectivity imparted to N-a,b-enoyl derivatives by g-sultam auxiliaries of type 1 2 ) and 2 [6], as rationalized by Kim and Curran [7], is modulated by the stereoelectronic influence of the N lone pair (lp). We stressed that this additional effect, which is, under unchelating conditions, either matching or mismatching the steric approach, depending on the syn-or anti-s-cis conformations of the N-a,b-enoyl side chain, results from a general anomeric influence [8] 3 ) of the N lp, through the sp 2 CO, on the LUMO p-facial electronic distribution of the reactive centers. The N lp is itself orientated by stabilization with the anti-periplanar SÀO 1 s* orbital. We later

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

“…8 -10), the diastereoselectivity diminished with respect to the increasing size of the nucleophile, meaning that the transition-state energy differences decrease for the transfer of bulky substituents. A similar trend was earlier observed for 18 ) C(2), and C(9) of minor diastereoisomer, at higher field by ca. 0.16 -0.19 and ca.…”

“…It is noteworthy that the addition of EtMgCl (2.5 molequiv., THF, À 788) in the presence of 2.5 mol-equiv. of either LiCl or [18]crown-6 ether [60] did not influence significantly the aggregation since 2d was isolated in 55 or 59% yield and 74 or 67% d.e., respectively. A different coordinating solvent such as chiral tetrahydro-2-methylfuran seems to be more influent as 5d was obtained in 69% yield but only 40% d.e.…”

Twisting and Turning the Sulfonamide Bond: A Synthetic, Quantum Chemical, and Crystallographic Study

“…Although sulfonamides have been widely used in various areas of science for nearly a century (e.g., the classical “sulfa drugs” , ), theoretical − and/or experimental ,,− studies related to the nature of the sulfonamide bond are surprisingly rare. Many of these works were performed at low level of theory and sometimes contradict each other (in particular, different conformers were identified as the global energy minima for acyclic sulfonamides).…”

Synthesis and [4+2] Cycloaddition of (2R,2′R)‐N,N′‐Fumaroylbis[fenchane‐8,2‐sultam] (=(2E)‐1,4‐Bis[(3aS,6S,7aR)‐1,4,5,6,7,7a‐hexahydro‐7,7‐dimethyl‐2,2‐dioxido‐3H‐3a,6‐methano‐2,1‐benzothiazol‐1‐yl]but‐2‐ene‐1,4‐dione) to Cyclopentadiene

“…For comparison with analogous known X-ray crystal-structure data of dienophiles (À)-1c,d obtained from the camphor-derived sultam [13] [14], we also acylated sultam ()-5a with the corresponding acyl chlorides Helvetica Chimica Acta ± Vol. 88 (2005) 2442 4 ) See acknowledgements as well as footnote 17 in [8]. 5 ) The absolute configuration of ()-(1S)-fenchone was earlier ascertained by chemical correlation with both (À)-(2S)-2-isopropyl-5-oxohexanoic acid and (À)-(2S)-2-isopropylglutaric acid [9], as well as by an X-ray structure analysis of (1S)-2-bromo-2-nitrofenchane [10].…”

“…) This is normal since protic solvents were not tested 8. ) See [2]for the values of p*, d, a, and b parameters of the different solvents used.…”