Herein we describe the development of a catalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzed by a newly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio-, diastereo-, and enantioselectivity. Our process tolerates a broad range of aldehydes in combination with diverse alkynyl-substituted ketene acetals. The reaction products can be readily derivatized to furnish a variety of highly substituted enantiomerically enriched building blocks.

We report the first total synthesis of (-)-17-nor-excelsinidine, a zwitterionic monoterpene indole alkaloid that displays an unusual N4-C16 connection. Inspired by the postulated biosynthesis, we explored an oxidative coupling approach from the geissoschizine framework to forge the key ammonium-acetate connection. Two strategies allowed us to achieve this goal, namely an intramolecular nucleophilic substitution on a 16-chlorolactam with the N4 nitrogen atom or a direct I -mediated N4-C16 oxidative coupling from the enolate of geissoschizine.

A new class of highly acidic confined imino-imidodiphosphate (iIDP) Brønsted acids catalyze the asymmetric Prins cyclization of both aliphatic and aromatic aldehydes. Diverse functionalized 4-methylenetetrahydropyrans are obtained in good to excellent yields and with good to excellent regio- and enantioselectivities. Our iIDP catalysts provide an efficient and scalable enantioselective approach to various fragrances, including rose oxide and doremox.

We report a full account of our efforts towards bioinspired oxidative cyclizations of geissochizine and analogs to mimic the biosynthesis of the mavacuran, akuammilan, and excelsinidine groups of monoterpene indole alkaloids. The construction of the A,B,C,D ring system of geissoschizine was first achieved by merging two known syntheses of this alkaloid. Modified Ma's oxidative conditions (KHMDS/I2) applied directly to geissoschizine induced formation of the N4–C16 bond encountered in the excelsinidines core. Identical conditions applied to C16‐dimethylmalonate‐containing N4‐quaternized substrates ended in the formation of the mavacurans core (N1–C16 bond). With this unified oxidative cyclization strategy: (–)‐17‐nor‐excelsinidine, (+)‐16‐epi‐pleiocarpamine, (+)‐16‐hydroxymethyl‐pleiocarpamine, 16‐formyl‐pleiocarpamine and (+)‐taberdivarine H were synthetized. We also report a shortened total synthesis of 16‐epi‐pleiocarpamine compared to our preliminary communication from a C16‐monoester analog. Alternatively, 17‐nor‐excelsinidine was synthesized via an intramolecular nucleophilic substitution of a 7‐membered ring α‐chlorolactam prepared from 16‐desformyl‐geissoschizine.

Herein we describe the development of ac atalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzedbyanewly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio-, diastereo-, and enantioselectivity.Our process tolerates ab road range of aldehydes in combination with diverse alkynyl-substituted ketene acetals.T he reaction products can be readily derivatized to furnish avariety of highly substituted enantiomerically enriched building blocks.Allenes are surprisingly abundant and found in hundreds of natural products with biological activity. [1] They are also attractive motifs for chemical synthesis owing to their unusual properties and reactivity.A sc umulated dienes,a llenes often display higher reactivity than their noncumulated analogues. Moreover,a llenes display ap eculiar axial chirality characterized by their elongated tetrahedral geometry.Over the past years,the allene scaffold has been exploited in different ways including to create versatile synthetic intermediates and chiral ligands for asymmetric catalysis. [2,3] Despite the demand for chiral allenes though, enantioselective methods for their synthesis are limited. Indeed, they are most commonly prepared by the resolution of racemic allenes and reactions involving chirality transfer from enantiomerically enriched propargyl alcohols or amines. [4][5][6] More recently,m etal-catalyzed asymmetric allene syntheses have also been reported. [7] In contrast, organocatalytic approaches still remain underexplored and are largely limited to di-or trisubstituted allenes. [8] As ignificant breakthrough in this area was made in 2013 by Maruoka and co-workers,w ho reported the asymmetric functionalization of cumulenolates under phase-transfer catalysis.T his methodology gave access to chiral tetrasubstituted allenes through alleno-Mannich and alkylation reactions. [9] However, the corresponding asymmetric aldol reaction remained challenging.R ecently,F eng and co-workers reported agold-catalyzed nucleophilic addition of racemic allenoates to isatins with high diastereo-and enantioselectivity. [10] We now report an unprecedented alkynylogous Mukaiyama aldol reaction, which is catalyzed by anewly designed chiral disulfonimide and provides tetrasubstituted allenoates with excellent diastereo-and enantioselectivity.Several challenges had to be considered in the design of an asymmetric alkynylogous Mukaiyama aldol reaction. In addition to the enantioselectivity issue,t wo different

A new and flexible approach toward the synthesis of 6,12-guaianolide anticancer drugs such as trilobolides or thapsigargin has been developed that could be applied to the preparation of analogues with a modified ring system. The synthesis starts from commercial 2-methylcyclopentane-1,3-dione, only relying on diastereoselective reactions for the construction of the stereogenic centers at C1, C3, C6, and C10 and features a high-yielding ring-closing enyne metathesis (RCEYM) step for the formation of the [5,7] bicyclic core.

The development of an intramolecular rhodium(I)-catalyzed Pauson-Khand reaction of alkoxyallene-ynes with a proximal alkoxy group is reported. This reaction, in the presence of a [Rh(cycloocta-1,5-diene)Cl]2/propane-1,3-diylbis(diphenylphosphane) system under a CO atmosphere, constitutes a powerful tool for selectively accessing carbo- and heterobicyclo[5.3.0] frameworks featuring an enol ether moiety. Through this procedure, a straightforward access to guaiane skeletons with a tertiary hydroxy group at the C10 position was achieved.

Reported is the enantioselective total syntheses of mavacuran alkaloids,( + +)-taberdivarine H, (+ +)-16-hydroxymethyl-pleiocarpamine,a nd (+ +)-16-epi-pleiocarpamine,a nd their postulated biosynthetic precursor 16-formyl-pleiocarpamine.This family of monoterpene indole alkaloids is atarget of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline.I nspired by the biosynthetic hypothesis,a no xidative coupling approach from the geissoschizine framework to form the N1ÀC16 bond was explored. Quaternization of the aliphatic nitrogen center was key to achieving the oxidative coupling induced by KHMDS/I 2 as it masks the nucleophilicity of the aliphatic nitrogen center and locksi nt he required cis conformation.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.Zuschriften Scheme 3. Synthesis of (+ +)-16-deformyl-geissoschizine [(+ +)-22], (+ +)-geissoschizine [(+ +)-1], and the geissoschizine malonate (À)-23 according to our previous work. [13] AIBN = 2,2'-azobisisobutyronitrile, Boc = tert-butoxycarbonyl, COD = 1,5-cyclooctadiene, DMAP = 4-(N,Ndimethylamino)pyridine, LDA = lithium diisopropylamide, TFA = trifluoroacetica cid.Scheme 4. Total synthesis of (+ +)-16-epi-pleiocarpamine [(+ +)-5]a nd (+ +)-16-hydroxymethyl pleiocarpamine[(+ +)-3]byN 1 ÀC16 oxidative cyclization from N4-PMB-geissoschizinium derivatives. DIBAL-H = diisobutylaluminum hydride, DMF = N,N-dimethylformamide, PMB = pmethoxybenzyl, TMS = trimethylsilyl.