Synthesis of a Six-Membered-Ring (2R)-10a-Homobornane-10a,2-sultam and Structural Comparison with Oppolzer's, Lang's, and King's Sultams

Abstract

The new six-membered-ring (2R)-10a-homobornane-10a,2-sultam (À)-3a was synthesized and its X-ray structural analysis was compared with that of the novel structure of the five-membered-ring (2R)-bornane-10,2sultam analogues (À)-1a,b as well as with that already published for the six-membered-ring trans-decalin-like sultam 4a. Based on DN** density-function calculations and X-ray crystallographic studies of the N-methylated analogues (À)-1e and 4b and by comparing with the conformation of the N-fluoro derivatives (À)-1c and ()-1d, the anomeric stabilization was estimated to be smaller than the 2.0 ± 2.5 kcal/mol earlier suggested. The direction of pyramidalization is rationalized in terms of H-bond and steric and electronic interactions and extended to the known toluenesultam derivatives 10a ± c. 2 ) For N lp through-bond and through-space directing interactions, initially suggested by M¸ller and Eschenmoser, see [10a]. For nonexhaustive more recent examples, see [10b ± g]. Cieplak also proposed a hyperconjugative influence of the N lp on the incipient bond-formation through the intermediacy of a sp 2 atom, see Schemes 85 and 86 as well as reference 105 in [11]. More recently, King et al. also suggested an anomeric stabilization [12a]. We now wish to report the synthesis of the tricyclic six-membered-ring sultam (À)-3a as well as its X-ray-structural analysis for comparison with those of (À)-1a,b,e and the racemic six-membered-ring trans-decalin-like sultams 4a,b [12a].Results. ± The commercially available ()-camphorsulfonyl chloride 5 was treated with CH 2 N 2 in Et 2 O to afford, after thermal treatment, the known unsaturated C 11 ketone ()-6 in 84% yield according to a previously reported procedure [13]. Further protection of the carbonyl moiety (ethylene glycol, TsOH, THF; 79% yield) followed by hydroboration (9-BBN, THF, 208, then NaOH, H 2 O 2 ; 90% yield) furnished the known primary alcohol (À)-7a [14] 3 ). This intermediate was then converted to the corresponding crude unreported mesylate (À)-7b (MsCl, CH 2 Cl 2 , Et 3 N, 08; 95% yield [16]) prior to an S N 2 displacement (AcSK, DMSO, 458; 96% yield [17]) to afford the thioacetate (À)-7c. Oxidation (30% H 2 O 2 solution, 85%, AcOH solution [18]), with concomitant deprotection, delivered the new sulfonic acid ()-8a in 92% isolated yield. A route similar to that earlier published by Oppolzer et al.[1] was then followed for the preparation of (À)-3a.Thus, treatment with SOCl 2 at 1008 [19] furnished the sulfonyl chloride (À)-8b in 63% yield 4 ). Rather than addition of gaseous NH 3 under anhydrous conditions [21], we preferred, for technical reasons, the NH 4 OH procedure initially reported by Sutherland and co-workers [22] and recently re-actualized by Davis et al. [19] and Capet et al. [23]. The new sulfonamide ()-8c, thus obtained in 69% yield, was then cyclized under basic conditions (NaOMe, MeOH [1]) to furnish the sulfonimine (À)-9 in 75% yield 5 ).Helvetica Chimica Acta ± Vol. 85 (2002) 1974 3 ) According to [15], a lower chemical yield was obtaine...

Conformationally Preorganized Diastereomeric Norbornane-Based Maltosides for Membrane Protein Study: Implications of Detergent Kink for Micellar Properties

“…Of the facial agents developed for membrane protein study, the current agents contain systematic chiral variation only in the lipophilic region. The distinct features of the norbornane scaffold are widely exploited where conformational preorganization is paramount: in peptidomimetics 24 and medicinal chemistry, 25 in supramolecular chemistry as photo-switchable ion carriers, 26a,b and as chiral auxiliaries for asymmetric synthesis. 26c–g However, they have not so far been applied to membrane protein research.…”

“…The distinct features of the norbornane scaffold are widely exploited where conformational preorganization is paramount: in peptidomimetics 24 and medicinal chemistry, 25 in supramolecular chemistry as photo-switchable ion carriers, 26a,b and as chiral auxiliaries for asymmetric synthesis. 26c–g However, they have not so far been applied to membrane protein research. In this study, two sets of stereoisomeric detergents with the norbornane linker were prepared and evaluated for their stabilization efficacy with four different membrane proteins including a G-protein coupled receptor (GPCR) and a membrane protein complex (GPCR:G-protein complex).…”

Conformations and Coherences in Structure Determination by Ultrafast Electron Diffraction

“…van der Waals radius of a Me group which reportedly equals 2.0 Å). [35] Interestingly, the calculated r C-C ( g ) = 1.537 Å is found to exceed r C-C ( t ) = 1.533 Å by only 0.004 Å. Calculated C…C Me /C Me… C Me nonbonded distances equal 2.56/3.93 and 2.58/3.19 Å in t - and g -conformers of n -butane, respectively.…”

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

“…± We recently presented and compared the X-ray structure analyses of both the (2R)-bornane-10,2-sultam ((À)-1a) and its six-membered ring homologue (2R)-10a-homobornane-10a,2-sultam [1]. We discussed the stereoelectronic influence of the N lone pair (lp) as well as the steric influence of the Me(8) substituent on the N pyramidalization as well as conformations and diastereoselectivities imparted by these structural changes during the [4 2] cycloaddition of cyclopenta-1,3-diene to their N,N'-fumaroylbis [sultam] derivatives in different solvents [2].…”

“…± Two years ago, after submission of our paper describing the structure of the camphor-derived sultam (À)-1a [1], Prof. King [6] suggested that there was a typographical error in which the SÀN (1.750(3) ä) and SÀC (1.688(4) ä) bond lengths had accidentally become swapped because there is no other crystallographic evidence in the literature to suggest that the SÀC bond length would be shorter than that of SÀN 3 ). We confirmed to him our original results but, after lengthy discussion, decided it best to redetermine the structure of (À)-1a 4 ).…”