Phosphine- and water-promoted pentannulative aldol reaction.

Herein, an efficient metal-free intramolecular aldol reaction for the synthesis of an unusual class of cyclopentanoids is described. The reaction of α-substituted dienones tethered with ketones in the presence of tributylphosphine and water provided aldols. The role of water was realised to be crucial for this transformation. Furthermore, isotopic labeling experiments provided vital information about the reaction mechanism.

A computational investigation of the solvent-dependent enantioselective intramolecular Morita-Baylis-Hillman reaction of enones.

The intramolecular Morita-Baylis-Hillman reaction of ß-mono and ß,ß-disubstituted enones shows high yields and stereo-selective products when the reaction is performed in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as a solvent. In this work, we carried out a computational study using the density functional Becke 3-(B3) parameter exchange and the Lee-Yang-Parr (LYP) correlation functional and 6-31+G* basis set. Two major steps i.e. C-C bond formation and proton transfer were analysed using different pathways. The calculations show a very low barrier (ΔG† = 0.23 kcal mol-1) for C-C bond formation in the case of an experimentally dominant product. For this pathway the subsequent proton transfer via the HFIP step has a barrier of 26.98 kcal mol-1. The same has been confirmed using a Molecular Electrostatic Potential (MESP), which shows a negative region in between CC in the transition state. In spite of high barriers for proton transfer, the intermediate products formed in this reaction pathway are thermodynamically more stable in comparison with other pathways. The thermodynamic stability of the final product in this pathway is observed to surpass all other effects in the presence of HFIP, thereby corroborating the experimentally observed enantioselectivity.

Morita-Baylis-Hillman Reaction of ß,ß-Disubstituted Enones: An Enantioselective Organocatalytic Approach for the Synthesis of Cyclopenta[b]annulated Arenes and Heteroarenes.

The first enantioselective organocatalytic intramolecular Morita-Baylis-Hillman (MBH) reaction of sterically highly demanding ß,ß-disubstituted enones is presented. The MBH reaction of ß,ß-disubstituted-α,ß-unsaturated electron-withdrawing systems was previously considered to be unfeasible. Towards this end, designer substrates, which under simple and practical reaction conditions generate a variety of cyclopenta[b]annulated arenes and heteroarenes in excellent enantiopurities and near-quantitative yields in remarkably short reaction times, are described. The reason for the unusually facile nature of this reaction is attributed to the synergy guided and entropically favored intramolecular reaction. Further, this strategy provides easy access to a substantial number of bioactive natural products and pharmaceutically significant compounds.

Phosphine-Catalyzed Intramolecular Vinylogous Aldol Reaction of α-Substituted Enones.

We demonstrate the first phosphine-catalyzed intramolecular vinylogous aldol reaction (IVAR) of α-substituted enones. This strategy provides access to various pentannulated (hetero)arenes and dibenzocycloheptanones incorporated with two contiguous stereocenters, one of which is an all-carbon quaternary center. The scope of this work is further broadened through elaborations of the IVAR adducts to (i) benzannulated nine-membered carbocyclic systems, (ii) interesting classes of 1,3-dienes, 1,3,5-trienes, and 1-yn-3,5-dienes, and (iii) the analogs of echinolactone D and russujaponol F.

Metal- and Hydride-Free Pentannulative Reductive Aldol Reaction.

Traditionally, the reductive aldol reaction is a metal-catalyzed and hydride-promoted coupling between enones and aldehydes. We present a phosphine-mediated diastereoselective intramolecular reductive aldol reaction of α-substituted dienones and aldehydes, which is metal-free and hydride-free. The synthetic utility of the reductive aldol adducts is demonstrated by elaborating them in one step to indeno[1,2- b]furanones, indeno[1,2- b]pyrans, and dibenzo[ a, h]azulen-8-ones.

Organocatalytic Strategies for the Synthesis of Cyclopenta-Fused Arenes and Heteroarenes.

Cyclopentanoids are omnipresent in natural products and pharmaceutically relevant compounds. Among them, cyclopenta-fused arenes and heteroarenes possess impressive biological properties and play significant role in materials science. Consequently, several notable methods have been developed for their synthesis over the years. In this review, we mainly described metal-free and organocatalytic approaches that led to the construction of pentannulated arenes and heteroarenes.

Recent metal-catalysed approaches for the synthesis of cyclopenta[b]indoles.

The cyclopenta[b]indole scaffold is ubiquitously present in several bioactive natural products and pharmaceutically interesting compounds. Of the numerous methods known for the synthesis of cyclopenta-fused indoles, this review highlights only the metal-catalysed approaches reported from the year 2015 onwards. This review encompasses our own efforts leading to the synthesis of cyclopentannulated indoles, in addition to the seminal contributions of several other researchers.

An enantioselective organocatalytic intramolecular Morita-Baylis-Hillman (IMBH) reaction of dienones, and elaboration of the IMBH adducts to fluorenones.

An enantioselective organocatalytic intramolecular Morita-Baylis-Hillman (IMBH) reaction of dienones is reported for the first time. This has been achieved by incorporating entropy and synergy considerations during the substrate design. The reaction conditions are thoroughly verified for an efficient synthesis of highly functionalised cyclopenta-fused arenes and heteroarenes in excellent yields and enantioselectivities. The synthetic utility of the IMBH-adducts has been demonstrated by transforming them into 3,4-disubstituted fluorenones in a serendipitous manner.