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. 2010 May 7;12(9):2084-7.
doi: 10.1021/ol100574y.

The tert-butylsulfinamide lynchpin in transition-metal-mediated multiscaffold library synthesis

Renato A Bauer  1 , Christine M DiBlasi, Derek S Tan
Affiliations

The tert-butylsulfinamide lynchpin in transition-metal-mediated multiscaffold library synthesis

Renato A Bauer et al. Org Lett. .

Abstract

A unified synthetic approach to diverse polycyclic scaffolds has been developed using transition-metal-mediated cycloaddition and cyclization reactions of enynes and diynes. The tert-butylsulfinamide group has been identified as a particularly versatile lynchpin in these reactions, with a reactivity profile uniquely suited for efficient, stereoselective substrate synthesis and downstream transformations. This approach provides 10 distinct, functionalized scaffold classes related to common core structures in alkaloid and terpenoid natural products.

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Figures

Figure 1
Figure 1
Principal component analysis of 20 structural and physicochemical descriptors of the 40 top-selling drugs, 60 diverse natural products, 20 polycyclic alkaloids and terpenoids, 20 ChemBridge and Chem Div library members, and 32 multiscaffold library members. Average values for each parameter are indicated by group.
Scheme 1
Scheme 1
Stereoselective Synthesis of Enynes and Diynes Using a t-Butylsulfinimide Tether.a a HMPA = hexamethylphosphoramide; LiHMDS = lithium hexamethyldisilazide; TBDPS = t-butyldiphenylsilyl; TBS = t-butyldimethylsilyl; TMS = trimethylsilyl.
Scheme 2
Scheme 2
Transition Metal-Mediated Cycloadditions and Cyclizations of t-Butylsulfinamide-Tethered Enynes 4a–d and Diynes 5a–da,b,c a See Tables 1 and 2 for results. b Subsequent Diels–Alder reactions also shown (center). c BINAP = 2,2´-bis(diphenylphosphino)-1,1´-binaphthyl; COD = 1,4-cyclooctadiene; Cp* = pentamethylcyclopentadienyl; m-CPBA = meta-chloroperbenzoic acid; DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; DMAD = dimethylacetylene dicarboxylate; Grubbs I = benzylidene-bis(tricyclohexylphosphine)dichloro-ruthenium; Grubbs II = benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(tricyclohexylphosphine)ruthenium; IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazoly-2-ylidene; Tf = trifluoromethanesulfonate.
Scheme 3
Scheme 3
Pauson-Khand Reactions of anti-Enynes 17a–d.
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References

    1. See Supporting Information for full details.

    1. Messer R, Fuhrer CA, Häner R. Curr. Opin. Chem. Biol. 2005;9:259–265. - PubMed
    2. Koch MA, Schuffenhauer A, Scheck M, Wetzel S, Casaulta M, Odermatt A, Ertl P, Waldmann H. Proc. Natl. Acad. Sci. U.S.A. 2005;102:17272–17277. - PMC - PubMed
    1. Tan DS. Nat. Chem. Biol. 2005;1:74–84. - PubMed
    2. Bauer RA, Wurst JM, Tan DS. Curr. Opin. Chem. Biol. 2010;14 in press; doi:10.1016/j.cbpa.2010.02.001. - PMC - PubMed

    1. For reviews, see: Burke MD, Schreiber SL. Angew. Chem., Int. Ed. 2004;43:46–58. Nielsen TE, Schreiber SL. Angew. Chem., Int. Ed. 2008;47:48–56.

    1. For selected key examples, see: Burke MD, Schreiber SL. Science. 2003;302:613–618. Taylor SJ, Taylor AM, Schreiber SL. Angew. Chem., Int. Ed. 2004;43:1681–1685. Oguri H, Schreiber SL. Org. Lett. 2005;7:47–50. Spiegel DA, Schroeder FC, Duvall JR, Schreiber SL. J. Am. Chem. Soc. 2006;128:14766–14767. Wyatt EE, Fergus S, Galloway WRJD, Bender A, Fox DJ, Plowright AT, Jessiman AS, Welch M, Spring DR. Chem. Commun. 2006:3296–3298.

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