Journal of the American Chemical Society
Page 4 of 6
the oxygen atoms and hence counterbalance possible dipole
repulsion. Indeed, Cs CO proved uniquely effective and selective
(4) Enthalpy peaks at the nine-membered ring, cf: Dunitz, J. D.; Prelog,
V. Röntgenographisch bestimmte Konformationen und Reaktivität
mittlerer Ringe. Angew. Chem. 1960, 72, 896-902.
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in transforming 25 into 28. Control experiments, however, had
to be carried out with ketoester 31 devoid of the cyclic carbonate
since attempted activation of 25 with organic bases met with
(5) Still, W. C.; Galynker, I. Chemical Consequences of Conformation
in Macrocyclic Compounds. An Effective Approach to Remote
Asymmetric Induction. Tetrahedron 1981, 37, 3981-3996.
3
3
failure. Thus, treatment of 31 with guanidine 33 gave product 32
(6) (a) Reyes, E.; Uria, U.; Carrillo, L.; Vicario, J. L. Transannular
featuring the opposite non-natural stereochemistry at the ring
junction (dr 20:1), whereas Cs CO resulted in a dr 1.2:1. This
2 3
notable difference highlights the critical role of the metal cation; it
suggests that a chelated enolate entertaining an extra transannular
contact, as tentatively drawn in F, accounts for the formation of 1.
Reactions in Asymmetric Total Synthesis. Tetrahedron 2014, 70, 9461-
9484. (b) Clarke, P. A.; Reeder, A. T.; Winn, J. Transannular Reactions in
the Synthesis of Natural Products. Synthesis 2009, 691-709.
(7) For (studies toward) natural product total syntheses based on
transannular Michael reactions, which illustrate the power and the
challenges, see the following and literature cited therein: (a) Evans, D. A.;
Scheerer, J. R. Polycyclic Molecules from Linear Precursors:
Stereoselective Synthesis of Clavolonine and Related Complex Structures.
Angew. Chem. Int. Ed. 2005, 44, 6038-6042. (b) Scheerer, J. R.;
Lawrence, J. F.; Wang, G. C.; Evans, D. A, Asymmetric Syntheis of
Salvinorin A, A Potent Opioid Receptor Antagonist. J. Am. Chem. Soc.
2007, 129, 8968-8969. (c) Snider, B. B.; Zhou, J. Synthesis of (+)-Sch
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The concise synthesis of the enticing nor-cembranoid
sinulariadiolide (1) outlined above capitalizes on a remarkable
transannular
Michael
addition/elimination/cyclization/oxa-
Michael cascade. While this transformation showcases the power
and intricacy of macrocyclic stereocontrol, the route to the
required precursor attests to the maturity of RCAM and catalytic
6
8
42305 by a Biomimetic Transannular Michael Reaction. Org. Lett. 2006,
, 1283-1286. (d) Xue, H.; Yang, J.; Gopal, P. Toward the Synthesis of
34
alkyne-trans-addition as the enabling downstream chemistry.
Norzoanthamine: Building Carbocyclic Core by a Transannular Michael
Reaction Cascade. Org. Lett. 2011, 13, 5696-5699. (e) Wzorek, J. S.;
Knöpfel, T. F.; Sapountzis, I.; Evans, D. A. A Macrocyclic Approach to
Tetracycline Natural Products. Investigation of Transannular Alkylations
and Michael Additions. Org. Lett. 2012, 14, 5840-5843. (f) Barfoot, C.
W.; Burns, A. R.; Edwards, M. G.; Kenworthy, M. N.; Ahmed, M.;
Shanahan, S. E.; Taylor, R. J. K. A Convergent Synthesis of the Tricyclic
Core of the Dictyosphaeric Acids. Org. Lett. 2008, 10, 353-356. (g)
Shimizi, I.; Nakagawa, H. Synthesis of ()-Jasmine Ketolactone by
Transannular Michael Reaction. Tetrahedron Lett. 1992, 33, 4957-4958.
(h) Matsuura, T.; Yamamura, S. A Synthetic Study of Euphoreppinol via
Transannular Cyclization Reaction from Lathyrane-type Skeleton.
Tetrahedron Lett. 2000, 41, 45805-4809. (i) Verma, S. K.; Fleischer, E.
B.; Moore, H. W. Synthesis of Angular Triquinanes from 1-
Alkynylbicyclo[3.2.0]hept-2-en-7-ones. A Tandem Alkoxy-Cope Ring
Expansion/Transannular Ring Closure Reaction. J. Org. Chem. 2000, 65,
8564-8573. (j) Magnus, P.; Booth, J.; Diorazio, L.; Donohoe, T.; Lynch,
V.; Magnus, N.; Mendoza, J.; Pye, P.; Tarrant, J. Taxane Diterpenes 2:
Synthesis of the 7-Deoxy ABC Taxane Skeleton and Reactions of the A-
Ring. Tetrahedron 1996, 52, 14103-14146.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on
the ACS Publications website at ##############
Experimental section including characterization data,
HPLC traces and NMR spectra of new compounds
Control experiments
AUTHOR INFORMATION
Corresponding Author
ORCHID
Alois Fürstner: 0000-0003-0098-3417
(8) In this context we refer to a previous biomimetic study, in which 2
Notes
had been converted by transannular Michael additions into the polycyclic
product ineleganolide; though elegant by design, the key step was low
yielding, cf.: Li, Y.; Pattenden, G. Biomimetic syntheses of ineleganolide
The authors declare no competing financial interests
and sinulochmodin
transannular Michael reactions. Tetrahedron 2011, 67, 10045-10052.
9) Kwan, E. E.; Scheerer, J. R.; Evans, D. A. The Stereochemical
Course of Intramolecular Michael Reactions. J. Org. Chem, 2013, 78,
75-303.
10) Ahn, N. T. Regio- and Stereo-Selectivities of Some Nucleophilic
C from 5-episinuleptolide via sequences of
ACKNOWLEDGMENT
(
Generous financial support by the MPG is gratefully
acknowledged. We thank the analytical departments of our
Institute for excellent cooperation.
1
(
Reactions. Top. Curr. Chem. 1980, 88, 145-162.
(11) Rummelt, S. M.; Radkowski, K.; Rosca, D.-A.; Fürstner, A.
Interligand Interactions Dictate the Regioselectivity of trans-
Hydrometalations and Related Reactions Catalyzed by [Cp*RuCl].
Hydrogen Bonding to a Chloride Ligand as Steering Principle in Catalysis.
J. Am. Chem. Soc. 2015, 137, 5506-5519.
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