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Review
. 2009;48(39):7140-65.
doi: 10.1002/anie.200902151.

Samarium diiodide mediated reactions in total synthesis

K C Nicolaou  1 , Shelby P Ellery, Jason S Chen
Affiliations
Review

Samarium diiodide mediated reactions in total synthesis

K C Nicolaou et al. Angew Chem Int Ed Engl. 2009.

Abstract

Introduced by Henri Kagan more than three decades ago, samarium diiodide (SmI(2)) has found increasing application in chemical synthesis. This single-electron reducing agent has been particularly useful in C-C bond formations, including those found in total synthesis endeavors. This Review highlights selected applications of SmI(2) in total synthesis, with special emphasis on novel transformations and mechanistic considerations. The examples discussed are both illustrative of the power of this reagent in the construction of complex molecules and inspirational for the design of synthetic strategies toward such targets, both natural and designed.

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Figures

Scheme 1
Scheme 1
Common mechanisms of SmI2-mediated activation of a) alkyl halides and b) carbonyl compounds.
Scheme 2
Scheme 2
Some representative SmI2-mediated transformations: a) Barbier, b) radical–alkene/alkyne, c) Reformatsky, d) carbonyl–alkene/alkyne, e) pinacol, f) fragmentation, and g) elimination reactions.
Scheme 3
Scheme 3
Formation of the 8-membered ring of vinigrol model 8 by a Barbier cyclization (Matsuda et al., 1997).[11]
Scheme 4
Scheme 4
Construction of phorbol system 11 by a Barbier cyclization (Carroll and Little, 2000).[12]
Scheme 5
Scheme 5
Synthesis of variecolin model 16 through halide-selective Barbier reactions (Molander et al., 2001).[14]
Scheme 6
Scheme 6
Barbier macrocyclization in a total synthesis of kendomycin (20) (Lowe and Panek, 2008).[16]
Scheme 7
Scheme 7
Application of a radical–alkyne cyclization in the synthesis of methyl-α-C-isomaltoside (23) and its peracetate (24) (Beau, Skrydstrup et al., 1994).[18]
Scheme 8
Scheme 8
Two possible mechanisms of SmIII enolate formation.
Scheme 9
Scheme 9
a) An unexpected intermolecular Reformatsky reaction/dimerization and b) an intermolecular Reformatsky reaction used in the total synthesis of acutiphycin (38) (Moslin and Jamison, 2006).[23]
Scheme 10
Scheme 10
An intramolecular Reformatsky reaction to form B ring system 40 during the total synthesis of Taxol® (41) (Mukaiyama et al., 1997).[26]
Scheme 11
Scheme 11
Formation of the A ring of Taxol® ABC model system 44 through an aldol-type reaction (Arseniyadis et al., 2005).[27]
Scheme 12
Scheme 12
Carbonyl–alkene cyclizations in the a) first- and b) second-generation total syntheses of patchoulenone (49) (Banwell et al., 1998).[32]
Scheme 13
Scheme 13
A carbonyl–alkene cyclization to complete the total synthesis of isoschizandrin (53) (Molander et al., 2003).[33]
Scheme 14
Scheme 14
A double carbonyl–alkene cyclization in the total synthesis of brevetoxin B (57) (Nakata et al., 2004).[37]
Scheme 15
Scheme 15
Carbonyl–alkene cyclizations in a) racemic and b) enantioselective total syntheses of platensimycin (61) (Nicolaou et al., 2006, 2007).[39,40]
Scheme 16
Scheme 16
Application of a carbonyl–alkene cyclization to a total synthesis and structural revision of laurentristich-4-ol (67) (Li et al., 2008).[41]
Scheme 17
Scheme 17
Synthesis of both enantiomers of 14-O-methyl pestalotiopsin (71) through a carbonyl–alkene cyclization (Procter et al., 2001, 2008).[42]
Scheme 18
Scheme 18
a) Carbonyl–alkene fragment coupling in the synthesis of phorbol system 11 and b) a stereochemically distinct coupling result (Carroll and Little, 2000).[12]
Scheme 19
Scheme 19
SmI2-mediated nitrone–acrylate reductive coupling in the total synthesis of hyacinthacine A2 (82) (Py et al., 2005).[44]
Scheme 20
Scheme 20
SmI2-mediated thioester–acrylate reductive coupling in the total synthesis of aliskiren (86) (Lindsay and Skrydstrup, 2006).[45]
Scheme 21
Scheme 21
Formation of welwitindolinone A isonitrile model 89 through SmI2-mediated isocyanate–alkene coupling (Wood et al., 2004, 2008).[47, 50]
Scheme 22
Scheme 22
Mechanism of the SmI2-mediated pinacol reaction.
Scheme 23
Scheme 23
Synthesis of rocaglamide diastereomer 97 through an intramolecular keto–nitrile pinacol reaction (Kraus and Sy, 1989).[58]
Scheme 24
Scheme 24
An aldehyde–oxime pinacol macrocyclization in the second total synthesis of diazonamide A (103) (Nicolaou et al., 2001, 2003).[61]
Scheme 25
Scheme 25
Cyclopropane fragmentation in the total synthesis of Taxol® (41) (Kuwajima et al., 1998).[64]
Scheme 26
Scheme 26
Synthesis of cyclocitrinol system 108 through a cyclopropane fragmentation/ring expansion (Schmalz et al., 2007).[65]
Scheme 27
Scheme 27
A cyclobutane fragmentation/ring expansion in the total synthesis of guanacastepenes A (111) and E (112) (Shipe and Sorensen, 2002).[66]
Scheme 28
Scheme 28
SmI2-promoted isoxazole ring cleavage in the total synthesis of epothilones A (117) and B (118) (Bode and Carreira, 2001).[67]
Scheme 29
Scheme 29
Synthesis of actinopyrone A (120) through an ε-elimination of a methoxy group (Tatsuta et al., 2006).[70]
Scheme 30
Scheme 30
Epoxide elimination in the total synthesis of Taxol® (41) (Danishefsky et al., 1995).[72]
Scheme 31
Scheme 31
Synthesis of dibromophakellstatin (126) through SmI2-mediated double deprotection (Lindel et al., 2005).[73]
Scheme 32
Scheme 32
a) A SmI2-mediated isomerization in the synthesis of monolomaiviticin aglycon (131) and b) application to the total synthesis of kinamycin C (134) (Nicolaou et al., 2009).[74, 75]
Scheme 33
Scheme 33
Synthesis of the BCD ring system (139) of penitrem D through a radical–alkene cyclization/Barbier-type reaction cascade (Curran et al., 2004).[76]
Scheme 34
Scheme 34
A reductive double enolate alkylation in the total synthesis of meso-chimonanthine (144) and meso-calycanthine (145) (Link and Overman, 1996).[77]
Scheme 35
Scheme 35
Synthesis of the C ring of a 19-hydroxy taxoid (149) through an epoxide fragmentation/aldol cyclization cascade (Mukaiyama et al., 2004, 2005).[79]
Scheme 36
Scheme 36
An elimination/Barbier cyclization cascade in the total synthesis of upial (155) (Yamada et al., 1993).[80]
Scheme 37
Scheme 37
A SmI2-promoted cyclization cascade in the total synthesis of martinellic acid (160) (Naito et al., 2008).[82]
Scheme 38
Scheme 38
SmI2-mediated ring closure in the total synthesis of the a) originally proposed (166) and b) corrected (169) structures of vannusal B (Nicolaou et al., 2008, 2009).[84, 85]
Scheme 39
Scheme 39
SmI2-mediated ring expansion in the total synthesis of sarcodonin G (174) (Piers et al., 2000).[86]
Scheme 40
Scheme 40
A palladium- and samarium-mediated cascade sequence in the synthesis of vitamin D3 analogs 179 and 180 (Aurrecoechea et al., 1989).[91]
Scheme 41
Scheme 41
Synthesis of lactarane system 184 through a cyclobutane/cyclopropane fragmentation cascade (Lange and Corelli, 2007).[93]
Scheme 42
Scheme 42
An unexpected cascade sequence during a guanacastepene model study (Shipe and Sorensen, 2006).[66]
Scheme 43
Scheme 43
A SmI2-promoted fragmentation/elimination/bromination cascade in the total synthesis of cortistatin A (196) (Baran et al., 2008).[95]
Scheme 44
Scheme 44
A SmI2-promoted radical cascade in the total synthesis of hypnophilin (203) and formal synthesis of coriolin (204) (Curran et al., 1988).[97]
Scheme 45
Scheme 45
a) A SmI2-mediated cascade in the synthesis of paeonilactone B (210) and b) clarification of the source of stereoinduction (Kilburn et al., 1998).[98]
Scheme 46
Scheme 46
Synthesis of PGG2 methyl ester (219) and 12-epi-PGG2 methyl ester (220) through a SmI2-catalyzed oxidative cascade (Corey and Wang, 1994).[101]
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References

    1. Namy JL, Girard P, Kagan HB. New J Chem. 1977;1:5–7.
    2. Girard P, Namy JL, Kagan HB. J Am Chem Soc. 1980;102:2693–2698.

    1. For selected reviews of SmI2-mediated reactions in organic synthesis, see: Soderquist JA. Aldrichimica Acta. 1991;24:15–23.Molander GA. Chem Rev. 1992;92:29–68.Molander GA. Org React. 1994;46:211–367.Imamoto T. Lanthanides in Organic Synthesis. Academic Press; London: 1994. p. 160.Molander GA, Harris CR. Chem Rev. 1996;96:307–338.Skrydstrup T. Angew Chem. 1997;109:355–358.Angew Chem Int Ed Engl. 1997;36:345–347.Molander GA, Harris CR. Tetrahedron. 1998;54:3321–3354.Nomura R, Endo T. Chem Eur J. 1998;4:1605–1610.Krief A, Laval AM. Chem Rev. 1999;99:745–777.Steel PG. J Chem Soc, Perkin Trans 1. 2001:2727–2751.Agarwal S, Greiner A. J Chem Soc, Perkin Trans 1. 2002:2033–2042.Kagan HB. Tetrahedron. 2003;59:10351–10372.Berndt M, Gross S, Hölemann A, Reissig HU. Synlett. 2004:422–438.Edmonds DJ, Johnston D, Procter DJ. Chem Rev. 2004;104:3371–3403.Jung DY, Kim YH. Synlett. 2005:3019–3032.Gopalaiah K, Kagan HB. New J Chem. 2008;32:607–637.Rudkin IM, Miller LC, Procter DJ. Organomet Chem. 2008;34:19–45.

    1. Shabangi M, Flowers RA., II Tetrahedron Lett. 1997;38:1137–1140.
    2. Flowers RA., II Synlett. 2008:1427–1439.

    1. For selected reviews of radical chemistry, see: Perkins MJ. Radical Chemistry. Ellis-Horwood; New York: 1994. p. 182.Curran DP. Aldrichimica Acta. 2000;33:104–110.Rozantsev EG, Loshadkin DV. Des Monomers Polym. 2001;4:281–300.Gansäuer A, Lauterbach T, Narayan S. Angew Chem. 2003;115:5714–5731.Angew Chem Int Ed. 2003;42:5556–5573.Hicks RG. Org Biomol Chem. 2007;5:1321–1338.

    1. For selected reviews of radical/ionic crossover reactions, see: Bashir N, Patro B, Murphy JA. Advances in Free Radical Chemistry. Jai Press; Stamford: 1999. p. 123.Godineau E, Schenk K, Landais Y. J Org Chem. 2008;73:6983–6993.

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