Synthesis of Substituted 1,3-Propanesultams from<i>N</i>-Substituted 2-Amino Alcohols

Cooper, Gary F.

doi:10.1055/s-1991-26593

Cited by 18 publications

(13 citation statements)

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“…19,20 It is noteworthy that the organoarsines with phenyl groups are more stable than the corresponding phosphines, although the tendency of the higher homologues to be oxidized increases in the case of aliphatic substituents. 21 The known optically pure (S)-prolinol bismesylate 22 gave the N-protected bromide 9 by Finkelstein reaction which afterwards was converted into the new ligand (S)-Ms-ProDPAs 10.…”

Section: Methodsmentioning

confidence: 99%

Chemistry in the Ambient Field of the Alkaloid Epibatidine, 2: Triphenylarsine as an Efficient Ligand in the Pd-Catalyzed Synthesis of Epibatidine and Analogs

Namyslo¹

1999

Synlett

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The key-step in the original synthesis of the N-protected form 4 of the highly analgetic, but also toxic alkaloid epibatidine (1) via Pd-catalyzed Heck-type hydroarylation gave only a moderate yield. With triphenylarsine as a ligand we obtained 4 in 81% yield and some partly new analogs 5 -8 in racemic form in 75 to 100% yield. Further attempts to optimize the ligand properties led to the combination of As and N donor centers. The N-protected pyrrolidine derivative 10 bearing a diphenylarsino substituent provided 4 in 92% yield.Epibatidine (1) 1 was isolated from an Ecuadorian poison frog and characterized by Daly in 1992. 2 From a synthetical viewpoint we have focused on a convergent synthesis using the Pd-catalyzed Heck-type hydro(het)arylation of an appropriate bicyclic alkene 2. Scheme 1After we had shown that a broad variety of both aryl and hetaryl components 3 can be attached to the bicyclic alkene norbornene by this reaction type we published recently the high-yielding synthesis of the N-protected epibatidine 4 and of some analogs 1 applying a modified hydroarylation procedure of Clayton and Regan. 4 For example, with triphenylphosphine as a ligand in the key-step we obtained N-methoxycarbonyl protected epibatidine 4 in up to 77% yield. Herein, we report the synthesis of 4 in yields up to 92% using ligands with arsine donor centers in the hydroarylation procedure. To the best of our knowledge, this synthetic pathway is hitherto the shortest route to the novel alkaloid 1 and together with our preliminary published synthesis of the azabicyclic alkene 2 1 , epibatidine 1 is now obtainable in 59% overall yield starting from bis(trimethylsilyl)acetylene.Apart from a few exceptions the use of arsine ligands in Pd-catalyzed reactions is a new synthetic procedure. An early application, for example, was published in 1989 by Trost and co-workers who used triphenylarsine in a Pdmediated cyclization of an allylic enyne. 5 Farina et al. 6 found an acceleration of the Stille-coupling and other recent examples also deal with Stille-7 and Suzuki-type 8 coupling reactions. The Pd-catalyzed cross-coupling reaction between organozinc halides and vinyl or aryl halides has been investigated by Rossi et al. 9 During our investigations Shibasaki documented Heck reactions performed with arsine ligands. 10 Using triphenylarsine as a ligand, the C-C coupling step of 2-chloro-5-iodopyridine (3) with 2 was completed within 2 hours. 11 We were very pleased to note that the undesired reduction of the aryl derivative 3 was driven back in favour of the reductive hetarylation. With different carbo-, azaand oxabicyclic alkenes we obtained the corresponding racemic hydroarylation products 5 -8 12 in yields ranging from 75 to 100% 13 (Scheme 2, Table 1). Scheme 2Thus, triphenylarsine is a soft ligand, suitable for Hecktype hydro-arylations, which enables high yields and short reaction times. We should emphasize that in the case of the benzo-anellated azabicyclic compound 7 the prelimiDownloaded by: Nanyang Technological University NTU. C...

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Section: Methodsmentioning

confidence: 99%

Chemistry in the Ambient Field of the Alkaloid Epibatidine, 2: Triphenylarsine as an Efficient Ligand in the Pd-Catalyzed Synthesis of Epibatidine and Analogs

Namyslo¹

1999

Synlett

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“…(5), 196 (23), 132 (18), 117 (8), 108 (33), 107 (7), 92 (8), 91 (100), 65 (6). MS (CI): m/z (%) = 668 (2), 364 (14), 320 (8), 268 (14), 240 (9), 228 (6), 213 (30), 207 (19), 152 (28), 119 (14), 118 (7), 116 (60), 92 (8), 91 (100), 65 (5). C 17 H 18 ClNO 4 S (367.84): calcd.…”

Section: (R)-(+)-3-(benzyloxycarbonylamino)nonane-1-sulfonylunclassified

“…13 C NMR (100 MHz, CDCl 3 ): δ = 21.0 (NCH 2 CH 2 ), 23.5, 24.8, 32.7 (11), 328 (7), 283 (21), 281 (11), 215 (8), 214 (12), 203 (34), 197 (9), 130 (16), 129 (100), 117 (17), 106 (7), 105 (47), 84 (24), 83 (37), 77 (8), 70 (9), 67 (9), 55 (11), 54 (7), 46 (7), 45 (16). MS (CI): m/z (%) = 411 (21), 410 (15), 409 (10), 363 (19), 357 (17), 330 (14), 329 (78), 327 (14), 311 (7), 281 (9), 245 (7), 243 (10), 217 (6), 216 (11), 214 (100), 203 (6), 197 (14), 132 (15), 129 (18), 105 (12). C 21 H 34 N 2 O 4 S (410.57) calcd.…”

Section: Cyclohexyl (Rs)-(-)-3-[2-(methoxymethyl)pyrrolidin-1-ylaminmentioning

confidence: 99%

“…0,128.1,128.5 (CPh) (11), 250 (22), 227 (6), 206 (13), 205 (6), 173 (10), 142 (14), 137 (5), 107 (6), 91 (45), 84 (7), 83 (100), 82 (18), 82 (70), 79 (10), 69 (20), 67 (12). HRMS, C 22 (6), 371 (20), 287 (9), 286 (53), 248 (21), 243 (10), 242 (62), 236 (14), 225 (11), 205 (6), 204 (38), 108 (18), 107 (8), 92 (8), 91 (100), 83 (5), 67 (6). MS (CI): m/z (%) = 454 (6), 354 (9), 264 (17), 221 (10), 173 (8), 108 (22), 107 (14), 95 (8), 92 (9), 91 (74), 84 (5), 83 (70), 82 (69), 81 (100), 80 (13), 79 (31), 69 (18), 67 (61).…”

Section: Cyclohexyl (R)-(-)-4-(benzyloxycarbonylamino)octanesulfonateunclassified

“…Among the various approaches to the title compounds are radical cyclisations, [8] intramolecular alkylations or sultam formation, [9] intramolecular aziridinations of unsaturated sulfonamides and rhodium-catalysed amidation, [10] 1,3-dipolar cycloadditions [11] and intramolecular Heck reactions. [12] Lee et al [13] and Cooper, [14] for instance, were able to synthesise chiral γ-sultams by intramolecular carbanion alkylation starting from the chiral β-amino alcohols. Furthermore, sultams can be synthesised by intraor intermolecular Diels-Alder reactions [15] and ring-closing metathesis.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric Synthesis of 3‐Substituted γ‐ and δ‐Sultams

2006

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An efficient and flexible asymmetric synthesis of various 3-substituted γ-and δ-sultams is described. The key step is a diastereoselective nucleophilic 1,2-addition of various organocerium compounds to the CN double bond of ω-SAMP-hydrazonosulfonates. The resulting hydrazines were obtained in good to excellent diastereomeric excesses (de = 78 to Ն 96 %). Removal of the chiral auxiliary by reductive N,N-bond cleavage afforded the corresponding aminosulfonates without racemisation. Ester hydrolysis and subsequent treatment

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Stereoselective Synthesis of β, γ‐Fused Bicyclic γ‐Ureasultams via an Intramolecular Mannich and aza‐Michael Addition Cascade

Yin,

Qu,

Chen

et al. 2024

Chemistry A European J

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A novel approach has been developed for the synthesis of bicyclic β, γ‐fused bicyclic γ‐ureasultams containing two consecutive chiral centers through an intramolecular Mannich and aza‐Michael Addition cascade of alkenyl sulfamides. The straightforward practical procedure and readily available starting materials enable the synthesis of variously substituted ureasultams. In addition, bicyclic γ‐ureasultams is a class of potential biotin analogues.

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Synthesis of Substituted 1,3-Propanesultams fromN-Substituted 2-Amino Alcohols

Cited by 18 publications

References 0 publications

Chemistry in the Ambient Field of the Alkaloid Epibatidine, 2: Triphenylarsine as an Efficient Ligand in the Pd-Catalyzed Synthesis of Epibatidine and Analogs

Chemistry in the Ambient Field of the Alkaloid Epibatidine, 2: Triphenylarsine as an Efficient Ligand in the Pd-Catalyzed Synthesis of Epibatidine and Analogs

Asymmetric Synthesis of 3‐Substituted γ‐ and δ‐Sultams

Stereoselective Synthesis of β, γ‐Fused Bicyclic γ‐Ureasultams via an Intramolecular Mannich and aza‐Michael Addition Cascade

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