Diiodomethane: a Versatile C1 Building Block

SPOTLIGHT ██1737

SYNLETT Diiodomethane:spotlight A Versatile C1 Spotlight 442 Building Block Compiled by Cláudia Diana C. B. G. Raposo This feature focuses on a reagent chosen by a postgradu- Cláudia Raposo was born in Oeiras, Portugal in 1987. She received ate, highlighting the uses and both her B.Sc. in Applied Chemistry and her M.Sc. in Bioorganic preparation of the reagent in Chemistry from the Faculdade de Ciências e Tecnologia of Univer- sidade Nova de Lisboa, Portugal, where she is currently working current research under the supervision of Dr. Krasimira Petrova. Her research is fo- cused on carbohydrate synthesis and glucose-containing nanoparti- cles for targeted drug delivery. REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal E-mail: [email protected]

Introduction iodomethylation,4 cyclopropanation,5 alkene reduction,6 and sigmatropic rearrangement.7 In the presence of metal- Diiodomethane, better known as methylene iodide, is a lic samarium, the air-sensitive samarium diiodide (SmI2) dense (3.325 g/mL at 25˚C), light-sensitive, pale-yellow is formed in situ; this is cheaper than buying samarium di- liquid. Because of its high density, it is used by the gemo- iodide.8 1 logical industry to determine the density of minerals. Be- Diiodomethane is commercially available, but can also be ing such an interesting compound, diiodomethane is a prepared by mixing methylene dichloride and sodium versatile C1 building block, which can be used to form car- iodide in dimethylformamide at a constant temperature of bon–carbon and carbon–heteroatom bonds. It is an easy- 100 °C for 6–8 hours.9 to-handle compound and can be used in a wide number of different reactions such as epoxidation,2 diazotization,3

Abstracts

(A) Alkylation of Diiodomethane R I MHMDS (M = Na, Li) I CH I Bull and Charette reported an improved procedure to obtain func- 2 2 R or I tionalized gem-diiodoalkanes with acceptable functional group tol- THF–Et2O (1:1) 40–90% yield erance towards olefins, acetals, ethers, carbamates, and hindered R Br –78 °C esters.10

O (B) β-Elimination of 2-Halogen-3-hydroxyesters and Synthesis of OH O (Z)-Vinyl Halides Sm, CH2I2 R1 OR3 R1 OR3 (E)-α,β-Unsaturated esters were synthesized from 2-halo-3-hy- THF, r.t. 2 X R2 R droxyesters in good to excellent yields using a mixture of metallic X = halogen X1 45–97% yield samarium and diiodomethane. (Z)-Vinyl halides can be obtained 1 Sm, CH2I2 X 2 R with high diastereoselectivities and yields from O-acetylated 1,1-di- X R H THF, r.t. iodo alcohols, metallic samarium, and diiodomethane in THF at OAc X1, X2 = halogen 41–98% yield room temperature.8

(C) Synthesis of 2,3-Dideuterioesters O D O The 1,4-reduction of α,β-unsaturated esters with D2O in the presence 1 3 Sm, CH2I2 of metallic samarium and diiodomethane afforded the corresponding R OR R1 OR3 2 D2O 2 2,3-dideuterioesters in good to excellent yields.6 R R D This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. 60–99% yield

(D) Transformation of Carbonyl Compounds into Epoxides O O Epoxides are important because they can be opened by a variety of MeLi 1 1 2 + CH2I2 R nucleophiles to afford 1,2-difunctionalized systems. Concellón et al. R R THF, 0 °C R2 reported a general, easy, and simple transformation of aldehydes and 70–95% yield ketones into epoxides with excellent yields using diiodomethane and methyllithium at 0 °C.2

SYNLETT 2013, 24, 1737–1738 Advanced online publication: 17.07.20130936-52141437-2096 DOI: 10.1055/s-0033-1338964; Art ID: ST-2013-V0449-V © Georg Thieme Verlag Stuttgart · New York 1738 C. D. C. B. G. Raposo SPOTLIGHT

1 4 (E) Synthesis of (E)-α-Hydroxy-β,γ-unsaturated Amides R CONR 2 1 O 4 Sm, CH I Concellón and co-workers11 reported an easy and simple procedure R CONR 2 2 2 OH 2 3 to prepare (E)-α-hydroxy-β,γ-unsaturated amides using metallic R2 R3 THF, r.t. R R samarium and diiodomethane with high regio- and diastereo- 68–85% yield selectivity.

(F) Cyclopropanation Et CONEt2 Cyclopropanation of alkenes can be carried out by a mixture of me- OH CONEt2 11 Et Sm, CH2I2 tallic samarium and diiodomethane. Cyclopropanation of terminal OH alkynes under the action of diiodomethane and triethylaluminum THF, r.t. 71% yield 5 CH I , Et Al 1 2 proceeded stereoselectively. 1 2 2 2 3 R R R R Et Et hexane, 20–25 °C

60–80% yield

(G) Iodomethylation of Amino Aldehydes O OH The halomethylation of carbonyl compounds is difficult to achieve R 1. Sm, CH I , THF, 0 °C R I H 2 2 due to the instability of halomethyllithium compounds. As an alter- 2. H O+ NBn 3 NBn native, Bernad et al. reported a smoothly proceeding reaction using 2 2 metallic samarium and diiodomethane.4 59–87% yield

(H) Double Carbonylation of Diiodomethane EtO OEt 1. CO, [Rh], (EtO)3CH Double carbonylation of diiodomethane in triethylorthoformate in CH2I2 2. ROH, (EtO)3CH O O the presence of catalytic amounts of rhodium complex gave diethyl- malonate in good yield.12 60% yield

(I) Sigmatropic Rearrangement O O Li and co-workers described an efficient method for the synthesis of R R = Ar R β-diketones from aromatic α-bromo ketones in the presence of di- O 40–85% yield Et Zn, CH I iodomethane and diethylzinc. Aliphatic α-bromomethyl ketones Br 2 2 2 R CH Cl O gave 2,4-disubstituted furans or cyclopropanols in moderate yield.7 2 2 R = Alk OH R R 48–50% yield

(J) Diazotization for the Synthesis of Aryl Iodides H2N CO2Et I CO2Et The reactions of aryl amines in the presence of isoamyl nitrite and isoamyl nitrite CH I diiodomethane formed aryl iodides cleanly and in good yield.3 N 2 2 N N 0–100 °C N H H 66% yield

(K) Coupling Molecules with a CH2 Linkage In the synthesis of ditopic ligands, bispyrazolylpyridine molecules NaH N Me N N can be coupled with CH2 linkages using sodium hydride and diiodo- N N N CH2I2 N Me N methane in dichloromethane with moderate yields, as reported by N NH THF Zadykowicz and Potvin.13 50% yield 2

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