Samarium Diiodide Acting on Acetone - Modeling Single Electron Transfer Energetics in Solution

Samarium diiodide is a versatile single electron transfer (SET) agent with various applications in organic chemistry. Lewis structures regularly insinuate the existence of a ketyl radical when samarium diiodide binds a carbonyl group. The study presented here investigates this electron transfer by the means of computational chemistry. All electron CASPT2 calculations with the inclusion of scalar relativistic effects predict an endotherm electron transfer from samarium diiodide to acetone. Energies calculated with the PBE0-D3(BJ) functional and a small core pseudopotential are in good agreement with CASPT2. The calculations confirm the experimentally measured increase of the samarium diiodide reduction potential through the addition of hexamethylphosphoramide also known as HMPA

Samarium(II)-Promoted Cyclizations of Nonactivated Indolyl Sulfinyl Imines to Polycyclic Tertiary Carbinamines

Samarium(II)-promoted cyclizations of N-acylated indolyl sulfinyl imines without electron-withdrawing groups at C-3 furnished tertiary carbinamines in good yield. Screening of the reaction conditions revealed that application of an excess of samarium diiodide in the presence of water and lithium bromide provided the cleanest reactions and the highest yields. The most striking observation during this investigation was the reductive detachment of the sulfur functional group, which most likely precedes the cyclization step. As consequence no enantioselectivity could be observed if enantiopure sulfinyl imines were employed. The mechanisms of the N−S cleavage and of the cyclization of the intermediate imines as well as the role of the additives are discussed. The presented method generates interesting polycyclic indoline derivatives; a cascade reaction involving an ethoxycarbonyl-substituted side-chain provided unique tetracyclic spiro-γ-lactams

Diastereoselective Dearomatizing Cyclizations of 5-Arylpentan-2-ones by Samarium Diiodide – A Computational Analysis

This study analyzes the samarium diiodide-promoted cyclizations of 5-arylpentan-2-ones to dearomatized bicyclic products utilizing density functional theory. The reaction involves a single electron transfer to the carbonyl group, which occurs synchronously with the rate determining cyclization event, and a second subsequent proton-coupled electron transfer. These redox reactions are accurately computed employing small core pseudo potentials explicitly involving all f-electrons of samarium. Comparison of the energies of the possible final products rules out thermodynamic control of the observed regio- and diastereoselectivities. Kinetic control via appropriate transition states is correctly predicted, but to obtain reasonable energy levels the influence of the co-solvent hexamethylphosphortriamide has to be estimated by using a correction term. The steric effect of the bulky samarium ligands is decisive for the observed stereoselectivity. Carbonyl groups in para-position of the aryl group change the regioselectivity of the cyclization and lead to spiro compounds. The computations suggest again kinetic control of this deviating outcome. However, the standard mechanism has to be modified and the involvement of a complex activated by two SmI2 moieties is proposed in which two electrons are transferred simultaneously to form the new C–C bond. Computation of model intermediates show the feasibility of this alternative mechanism

Cyclizations Producing Hydrindanones with Two Methyl Groups at the Juncture Positions Mediated by Samarium Diiodide and Electrolysis

One-electron reductive intramolecular cyclization of enones with ketones or aldehydes mediated by samarium diiodide and electrolysis to afford cis-trimethyl- hydrindanolones. The reactions gave selectivities ranging from 1:1 to 100:0 depending on the conditions

Synthesis of carbohydrate-derived (Z)-vinyl halides and silanes: Samarium-promoted stereoselective 1,2-elimination on sugar-derived a-halomethylcarbinol acetates

Thanks are due to the Spanish Ministerio de Economía y Competitividad (CTQ2010-14959, CTQ2014-55015-P), for financial support. University of Aveiro and FCT/MEC for the financial support of the QOPNA research unit (FCTUID/QUI/00062/2013) through national funds and, where applicable, co-financed by the FEDER,within the PT2020 Partnership Agreement, and to the Portuguese NMR Network

Samarium(II) folding cascades involving hydrogen atom transfer for the synthesis of complex polycycles

The expedient assembly of complex, natural product-like small molecules can deliver new chemical entities with the potential to interact with biological systems and inspire the development of new drugs and probes for biology. Diversity-oriented synthesis is a particularly attractive strategy for the delivery of complex molecules in which the 3-dimensional architecture varies across the collection. Here we describe a folding cascade approach to complex polycyclic systems bearing multiple stereocentres mediated by reductive single electron transfer (SET) from SmI2. Simple, linear substrates undergo three different folding pathways triggered by reductive SET. Two of the radical cascade pathways involve the activation and functionalization of otherwise inert secondary alkyl and benzylic groups by 1,5-hydrogen atom transfer (HAT). Combination of SmI2, a privileged reagent for cascade reactions, and 1,5-HAT can lead to complexity-generating radical sequences that unlock access to diverse structures not readily accessible by other means

Development of Regio- and Diastereoselective Samarium (II) Iodide Mediated Allylic Benzoate Reductions

Herein, we report a regio- and diastereoselective samarium mediated allylic benzoate reduction. The reaction can achieve high yields, regioselectivity, and diastereoselectivity, however there appear to be many factors influencing the outcome: proton sources, alkene geometry, chelating group length, relative stereocenter positioning, and stereocenter identity. These substrate parameters were looked at in-depth which ultimately led to several conclusions about optimized substrates. For instance, experiments indicate that the reaction proceeds through a bicyclic organosamarium species followed by intramolecular protonation from samarium bound water

Samarium Diiodide Mediated Reductive Coupling of Epoxides and Carbonyl Compounds: A New Stereocontrolled Synthesis of C-Glycosides from 1,2-Anhydro Sugars

The significant advances in the understanding of the biological function of carbohydrates and glycoconjugates achieved during the last two decades have stimulated the development of glycomimetics as fundamental tools for biological research and as potential agents for therapeutic intervention. C-Glycosides are of special relevance in this context due to their resistance to hydrolysis and to their occurrence in a number of natural products with interesting biological activity. Methods for their preparation using anomeric anions, cations, radicals, and carbenes have been extensively studied. 1,2-Anhydro sugars, readily available and well-known donors for the stereoselective preparation of O-glycosides, have also found application in the stereoselective synthesis of C-glycosides.This work was supported by the Ministry of Science and Technology of Spain (project BQU2000-1501-C02-01).Peer reviewe