Samarium iodide synthesis

Zard and coworkers have developed a synthesis of substituted dienes by reductive elimination of allylic nitroacetates (equation 33)66. Allylic nitroacetates can be prepared by condensation of nitromethane with the carbonyl compound followed by addition of formaldehyde and acetylation67. Reductive elimination can be carried out by employing either chromous acetate or samarium iodide. 

The reductive elimination of 0-hydroxyimidazoyl sulfones by samarium iodide was claimed to be an improved variation of the Julia olefin synthesis [421]. 

Scheme 35 Samarium iodide-promoted synthesis of spirooxindoles related to welwitin-dolinone A...

In the stereoselective synthesis of epothilone A (11), Carreira used a syn -reduction methodology in the synthesis of the key intermediate (14)9 (Scheme 4.If). Reduction of the isoxazoline 12 with samarium iodide at 0 C in THF gave the ketone 13. Narasaka reduction of the P-hydroxy ketone 13 using triethylb-orane/sodium borohydride afforded the. syn-diol 14 in high yield and with high diastereoselectivity. 

P. Girard, J. L. Namy, and H. B. Kagan, Divalent lanthanide derivatives in organic synthesis. 1. Mild preparation of samarium iodide and ytterbium iodide and their use as reducing or coupling agents,. /. Am. Chem. Soc., 102 (1980) 2693-2698. 

Konieczny, M.T., Toma, PH., and Cushman, M., Synthesis of hydroxyethylene isosteres of the transition state of the HIV protease-catalyzed Phe-Pro hydrolysis. Reaction of 2-[(Boc)amino]-l-(2 -oxocyclopentyl)-3-phenylpropanols with diethyl phosphorocyanidate and lithium cyanide followed by samarium iodide, J. Org. Chem., 58, 4619, 1993. 

The reaction of a ketone with an allyl acetate in the presence of samarium iodide catalyzed by palladium (Pd°) has been applied to an intramolecular addition. The keto acetate 546 [prepared from neryl acetate (27 acetate)] was cyclized to l-menthen-4-ol ( 4-terpinenol 547) in 62% yield using 5 mol% of Pd(PPh3)4. Separation of the (+)- and (- )-isomers of 547 has been achieved on Chirasil-Val columns. The synthesis by Delay and Ohloff of optically active l,8-menthadien-4-ol (548) (Vol. 4, p. 511, Ref. 382) encountered difficulties when it was carried out on a larger scale. They then attempted to... 

The samarium iodide promoted reduction of substrate 242 also led to ring opening to yield hydroxycyclohexenone 243 in De Clercq s synthesis of a precursor to the A-ring of 1 a-hydroxyvitamin D3, Eq. 148 [196]. 

Samarium iodide has been used to reduce sulfonylated oxabicydic substrates leading to the elimination of the ft oxygen moiety. Molander used this strategy for the synthesis of substituted cycloheptenes and cyclooctenes, Eq. 155 [81]. 

The first total synthesis of ( )-oxerine (8) was performed by Aoyagi and co-workers (187), and is shown in Scheme 6. The route is based on the use of a samarium iodide-mediated intramolecular cyclization as the key... 

Samarium iodide has been utilized in the synthesis of the antineoplastic macrolidc antibiotic cytovaricin 55. The high equatorioselectivity and chemoselecti vity make samarium iodide36 the reagent of choice for this reduction. 

Other reducing agents, such as sodium/ammonia or diphenylstannane are unsatisfactory55. Since stereoselective reductions of this type have been a problem in the synthesis of milbemycins and avermectins57. the utility of the radical anion reduction via samarium diiodide/proton donor remains to be appreciated generally. For routine applications on a multigram scale, the price of samarium iodide is currently too high (1 mol of samarium costs ca. 25 times more than 1 mol of lithium). 

Cossy has reported a synthesis of a-kainic acid that establishes the stereogenic centers on a preformed pyrrolidine ring (Eq. 20) [40], Thus, ketone 57 was prepared from L-pyroglutamic acid in 11 steps. Samarium iodide-mediated cyclization of 57 gave 58 as a mixture of stereoisomers at the carbinol carbon. Dehydration gave 59, and a 6-step sequence, starting with oxidative cleavage of the double bond, provided a-kainic acid. One notable aspect of this synthesis is the use of an enamide as a free-radical acceptor in the key cyclization. This process has been used in a number of alkaloid syntheses as will be seen in the next section. 

Synthesis of Alkenes by Reductive Elimination. The treatment of 2-halo-3-hydroxy esters and amides with samarium iodide leads to the corresponding di- or trisubstituted E)-a,p-unsaturated derivatives in high yields and diastereoselectivities (eqs 39 and 40). The precursors are readily accessible by condensation of the lithium enolate of a-haloesters or amides. If the substrate contains y,i5-unsaturation, the /3,y-unsaturated ester is generated in the process (eq 41). 

Samarium iodide can also be used as an alternative to sodium/ mercury amalgam for the reductive elimination of 1,2-acetoxy-sulfones in the Julia-Lythgoe olefination. The alkene is generated in a two-step process that first involves DBU or LDA treatment to generate a vinyl sulfone that is then reductively cleaved with samarium iodide (eq 44). The diastereoselectivity of both transformations is usually quite good and the method is compatible with the synthesis of monoalkenes as well as dienes and trienes. 

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