Humberto Rodríguez-Solla

β-Elimination reactions by using samarium diiodide

The development of methodologies for the formation of carbon–carbon double bonds could be considered one of the most important challenges in organic synthesis. To this end, β-elimination reactions in 1,2-difunctionalised substrates have been one of the most important means of generating CC bonds. n This review is intended to highlight the use of SmI2 in β-elimination procedures, such that the organization of this revision highlights conventional β-elimination processes which are promoted by samarium diiodide. The synthetic applications of SmI2 will be covered, and 1,2-elimination reactions which are involved in sequential reactions promoted by samarium diiodide, will also be illustrated. These methodologies along with the more recent developments in the area are discussed in this tutorial review.

Sequential Elimination–Reduction Reactions Promoted by Samarium Diiodide: Synthesis of 2,3‐Dideuterioesters or ‐amides

A facile and general sequential elimination/reduction process promoted by samarium diiodide provides an efficient method for synthesizing saturated esters or amides 3 from readily available starting materials. The reaction involves a beta-elimination of the starting 2-halo-3-hydroxyesters or -amides 1 and subsequent 1,4-reduction of the obtained alpha,beta-unsaturated esters or amides in the presence of H2O. When D20 is used instead of H2O, 2,3-dideuterioesters or -amides 4 are isolated. A mechanism is proposed to account for this synthesis.

Synthesis of Isotopically Labeled (E)‐β,γ‐Unsaturated Esters with Total or High Diastereoselectivity by Using Samarium Diiodide

A simple, efficient, highly diastereoselective method for preparing (E)-α,δ-dideuterio-β,γ-unsaturated esters: SmI2 -promoted reduction/elimination of α-halo-β-hydroxy-γ,δ-unsaturated esters in the presence of D2 O. This provides the desired products in which the C-C double bond is generated with total or high diastereoselectivity.

Synthesis of Different Deuterated Carboxylic Acids from Unsaturated Acids Promoted by Samarium Diiodide and D2O

An easy, and rapid reduction of the Cdbond;C bond of alpha,beta-unsaturated acids by means of samarium diiodide in the presence of D(2)O provides an efficient method for synthesizing 2,3-dideuterio acids. Starting from alka-2,4-dienoic acids, (E)-alpha,delta-dideuterio-betagamma-unsaturated acids are obtained, the new Cdbond;C bond being generated with complete diastereoselectivity. When H(2)O is used instead of D(2)O, saturated carboxylic acids and (E)-beta,gamma-unsaturated acids are isolated. A mechanism to explain each synthesis has been proposed.

Synthesis of (E)-α,β-Unsaturated Amides with High Selectivity by Using Samarium Diiodide

Stereoselective β-elimination of 2-chloro-3-hydroxyamides 1 is achieved by using samarium diiodide to yield α,β-unsaturated amides 2, in which the C=C bond is di- tri-, or tetrasubstituted. The starting compounds 1 are easily prepared by reaction of the corresponding lithium enolates of α-chloroamides with aldehydes or ketones at −78u2009°C. The influence of the reaction conditions and the structure of the starting compounds on the stereoselectivity of the β-elimination reaction is also discussed.

Highly enantioselective synthesis of α-azido-β-hydroxy methyl ketones catalyzed by a cooperative proline–guanidinium salt system

The combined activity of (S)-proline and an achiral tetraphenylborate TBD-derived guanidinium salt permits the aldol reaction between azidoacetone and aromatic, or heteroaromatic aldehydes. The α-azido-β-hydroxy methyl ketones obtained as products can be isolated in good yield, with high diastereo- and enantioselectivity.

Recent Synthetic Applications of Manganese in Organic Synthesis

While the organometallic compounds derived from many metals have found a broad application in organic synthesis, the use of organomanganese compounds has only recently been developed due to the passivity exhibited by commercial Mn in the direct metalation of organic compounds. In this Concept article, we highlight the potential of manganese and its organometallic compounds in organic synthesis by illustration of the studies previously reported by others and our laboratory in this field. Based on the transformations reported herein, organomanganese compounds could become important tools in the future of the organic synthesis, due to their high selectivity.

Synthesis of enantiopure 2-C-glycosyl-3-nitrochromenes.

A novel methodology has been developed to obtain enantiopure 2-C-glycosyl-3-nitrochromenes. First, (Z)-1-bromo-1-nitroalkenes were prepared from the corresponding sugar aldehydes through a sodium iodide-catalyzed Henry reaction with bromonitromethane followed by elimination of the resulting 1-bromo-1-nitroalkan-2-ols. In the next step, reaction of the sugar-derived (Z)-1-bromo-1-nitroalkenes with o-hydroxybenzaldehydes afforded enantiopure (2S,3S,4S)-3-bromo-3,4-dihydro-4-hydroxy-3-nitro-2H-1-benzopyrans, which, upon SmI2-promoted β-elimination, yielded chiral enantiopure 2-C-glycosyl-3-nitrochromenes.

Synthesis of (E)‐α,β‐Unsaturated Esters and (Z)‐Vinyl Halides with Total or High Diastereoselectivity by Using Samarium Metal

A highly diastereoselective β-elimination of 2-halo-3-hydroxy esters 1 or O-acetylated 1,1-dihaloalkan-2-ols 4 is achieved with samarium in the presence of diiodomethane, yielding α,β-unsaturated esters 2 or vinyl halides 5, respectively. The β-elimination reaction was promoted by samarium diiodide, which was generated in situ. The starting halohydrins 1 or 4 are easily prepared by reaction of the corresponding lithium enolates of α-halo esters or dihalomethyllithium with aldehydes at −78 °C. The influence of the reaction conditions and the structure of the starting compounds on the diastereoselectivity of the β-elimination reactions is discussed. A comparative study of the β-elimination reaction with preformed SmI2 and metallic samarium is also performed. These elimination reactions can be explained by the proposed mechanism. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Detection of sulfenic acid in intact proteins by mass spectrometric techniques: application to serum samples

Formation of cysteine sulfenic acid (SA) is considered a transient state of thiol oxidation in living organisms that can be either reduced back or continue to result in the formation of sulfinic and sulfonic acids. As any disturbance in oxidation is correlated to age-related diseases such as cancer and Alzheimers disease, the detection of SA transient state formed a sensor for such redox-mediated events. Thus, detection of low amounts of SA is critical in order to prevent further oxidative damage of cells and tissues and for this aim specific strategies have to be developed. In this work, detection and quantification of induced SA in human serum albumin is reported by specific capture using alkyne β-ketoester (KE) previously linked to a lanthanide (Ln)-containing chelator (Ln–DOTA, where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). SA formation was induced by hydrogen peroxide to mimic oxidative conditions produced in living cells by ROS and was detected using molecular and elemental mass spectrometric (MS) techniques. The developed strategy has been further applied to the determination of SA-induced formation in human serum by using affinity chromatography for purification of albumin followed by inductively coupled plasma mass spectrometry (ICP-MS) to monitor the formed SA linked to Ln–DOTA–KE in combination with isotope dilution analysis (IDA) for absolute quantification. Quantitative results showed levels of oxidative damage regarding SA formation in up to 40% of the albumin present.