A new route to obtain the polyalkylated indole (+/-)-trans-trikentrin A was developed. The synthesis of this natural alkaloid features a thallium(III)-mediated ring contraction reaction to obtain the trans-1,3-disubstituted five-membered ring in a diastereoselective manner. Thallium(III) is chemoselective in this rearrangement, reacting with the olefin without oxidation of the indole moiety. Other key transformations are the Bartoli's reaction to construct the heterocyclic ring and a Heck coupling to add the carbons atom that will originate the nonaromatic cycle.

Regarding all the green aspects of sustainable chemical transformations, eco-friendly processes along with economic development, environmental protection as well as natural resources preservation are mandatory. The use of unconventional media for organic transformations has been part of the quest for new eco-friendly process. As new alternative media for volatile organic solvents, deep eutectic solvents (DES) can be defined as the eutectic mixtures formed of two or more phase-immiscible components, which furnish a new homogeneous liquid phase with lower freezing point than those observed for individual counterparts. They found applications in several different fields, such as solvent/catalyst for organic transformations, biotransformations, and polymerization reactions, metal and biomass processing applications, and separation technologies. This review describes the recent studies on the use of deep eutectic mixtures as solvent and/or catalyst for multicomponent reactions in the synthesis of complex organic compounds.

No abstract

A new approach to the synthesis of cyclopenta[g]indole derivatives possessing structural features of natural alkaloids, such as trikentrins and herbindols, is described. The key step in the sequence is a thallium(III)-mediated ring-contraction reaction to transform a cyclohexene moiety into a functionalized cyclopentyl unit.Cycloalkylindole alkaloids constitute a large number of compounds, on which usually the carbocyclic moiety is fused to the C2-C3 position. 1,2 However, the cytotoxic herbindoles and trikentrins, that were isolated from marine sponges, feature an unusual skeleton, on which the cyclopentane ring is fused to the C6-C7 position. In addition, there is no substituent at the C2 and the C3 positions ( Figure 1). 3 Furthermore, synthetic molecules with similar tricyclic ring systems can inhibit the human nonpancreatic secretory phospholipase A 2 , which is associated with some diseases including arthritis, septic shock and atherosclerosis. 4 Thus, several approaches have been developed to construct the challenging framework of these bioactive natural molecules. 5 Figure 1 Structure of cis-and trans-trikentrin AWe considered that a ring-contraction approach could be used to obtain the cyclopentane ring of this class of alkaloids. A reagent that could efficiently promote this rearrangement would be thallium trinitrate (TTN), 6,7 which has already been used in the synthesis of several indanes through the rearrangement of 1,2-dihydronaphthalenes (Scheme 1), 8 including the total synthesis of the sesquiterpene (±)-mutisianthol. 8b Based on these results, we herein present the synthesis of new cyclopenta[g]indole derivatives, such as 1, through the thallium(III)-mediated ringcontraction reaction of the six-membered-ring substrate 2 (Scheme 2). Scheme 1 Scheme 2Indoles are known to be very reactive toward electrophilic species, particularly at the 3-position. Among the electrophiles utilized in functionalizations of indoles are thallium(III) salts, such as thallium tris-trifluoroacetate (TTFA) and thallium triacetate (TTA). 9 In this scenario, we started the present work investigating the reactivity of the N-protected indole 3 with TTN, using one of the standard conditions for the ring-contraction reaction. 8a This reaction gave the indoline derivatives 4, 5, and 6 in 23%, 40%, and 9% isolated yields, respectively (Scheme 3). Considering the behavior of the indole 3, the main challenge to obtain the desired cyclopenta[g]indole 1 using thallium(III) would be the discovery of a reaction condition that could promote the rearrangement of the indole 2, avoiding the oxidation of its very reactive C3 position.The indoline 4 is a crystalline solid, whose X-ray crystal structure analysis showed a trans relationship between the nitrate and methoxy groups ( Figure 2). Thus, by analogy with the NMR data of compound 4, the relative configuration of the trans-dimethoxy derivative 5 could be assigned. The NMR data of the indolines 4, 5 and 6 deserve some comments. The signals of H a in 4 and 5 are broad singlets. On the oth...

No abstract

A divergent enantioselective synthesis of (nor)illudalane sesquiterpenes was designed by using a Pd 0catalyzed asymmetric C(sp 3 )−H arylation as a key step to control the isolated, highly symmetric quaternary stereocenter of the target molecules. A matched combination of chiral substrate and catalyst proved optimal to reach good levels of stereoselectivity. This approach enabled the synthesis of three (nor)illudalanes, including (S)-deliquinone and (S)-russujaponol F, which are synthesized for the first time in enantioenriched form.

Three (nor)illudalane sesquiterpenes were synthesized from a common intermediate in racemic and enantioenriched forms using Pd 0-catalyzed C(sp 3)−H arylation as a key step. The configuration of the isolated, highly symmetric quaternary stereocenter of the target molecules was controlled through a matched combination of chiral substrate and catalyst. Moreover, the recently developed Ir-catalyzed C−H borylation/Cu-catalyzed methylation method was employed to install the methyl group on the benzene ring. This strategy allowed the efficient synthesis of both racemic and (S)-configured puraquinonic acid, deliquinone, and russujaponol F. a Reagents and conditions: (a) HBr aq., AcOH, reflux; (b) KHCO 3 , MeI, DMF, 40°C, then NaH, allyl bromide; (c) PhNEt 2 , 200°C; (d) OsO 4 (5 mol %), NaIO 4 , AcOEt/H 2 O, 25°C; (e) NaBH 4 , MeOH, 0°C ; (f) salcomine hydrate, O 2 atm., MeCN, 25°C; (g) AcOH, AgNO 3 , (NH 4) 2 S 2 O 8 , MeCN/H 2 O, 70°C.

Several syntheses have already been reported for cis‐trikentrins and herbindoles, which are indole alkaloids unsubstituted at the C2 and C3 positions that bear a trans‐1,3‐dimethylcyclopentyl unit. Herein, we describe the first asymmetric and stereoselective synthesis of the more challenging trans‐trikentrin A as its naturally occurring isomer. Different approaches were investigated and the strategy of choice was a combination of an enzymatic kinetic resolution and a thallium(III)‐mediated ring contraction. The antiproliferative activities of the natural product and related intermediates have been tested against human tumor cell lines, leading to the discovery of new compounds with potent antitumor activity.