Journal of the American Chemical Society
Communication
Potential for Progression in Neurodegenerative Disease Studies.
Chaykovsky, M. Dimethyloxosulfonium Methylide ((CH ) SOCH )
3
2
2
Biochem. Pharmacol. 2018, 155, 61−70.
and Dimethylsulfonium Methylide ((CH ) SCH ). Formation and
Application to Organic Synthesis. J. Am. Chem. Soc. 1965, 87, 1353−
1364.
(28) Toivola, R. J.; Savilampi, S. K.; Koskinen, A. The First Direct
Synthesis of Bicyclo[4.2.0]Oct-1(6)-en-7-One. Tetrahedron Lett.
2000, 41, 6207−6210.
3 2 2
(
15) Allinger, N. L.; Hirsch, J. A.; Miller, M. A.; Tyminski, I. J.; Van
Catledge, F. A. Conformational Analysis 0.60. Improved Calculations
of Structures and Energies of Hydrocarbons by Westheimer Method.
J. Am. Chem. Soc. 1968, 90, 1199−1210.
(
16) Selected examples of syntheses of trans 5−5 containing natural
products: (a) Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber,
S. L. Cobalt-Mediated Total Synthesis of (+)-Epoxydictymene. J. Am.
Chem. Soc. 1994, 116, 5505−5506. (b) Seiple, I. B.; Su, S.; Young, I.
S.; Lewis, C. A.; Yamaguchi, J.; Baran, P. S. Total Synthesis of
Palau’amine. Angew. Chem., Int. Ed. 2010, 49, 1095−1098. (c) Pronin,
S. V.; Shenvi, R. A. Synthesis of Highly Strained Terpenes by Non-
Stop Tail-to-Head Polycyclization. Nat. Chem. 2012, 4, 915−920.
(29) Garnsey, M. R.; Slutskyy, Y.; Jamison, C. R.; Zhao, P.; Lee, J.;
Rhee, Y. H.; Overman, L. E. Short Enantioselective Total Syntheses of
Cheloviolenes A and B and Dendrillolide C via Convergent Fragment
Coupling Using a Tertiary Carbon Radical. J. Org. Chem. 2018, 83,
6958−6976.
(30) Barton, D. H. R.; O’Brien, R. E.; Sternhell, S. 88. A New
Reaction of Hydrazones. J. Chem. Soc. 1962, 470−477.
(31) (a) Bouveault, L. Methods of Preparation of Saturated
Aldehydes of the Aliphatic Series. Bull. Soc. Chim. Fr. 1904, 31,
1306−1322. (b) Kleinnijenhuis, R. A.; Timmer, B. J. J.; Lutteke, G.;
Smits, J. M. M.; de Gelder, R.; van Maarseveen, J. H.; Hiemstra, H.
Formal Synthesis of Solanoeclepin A: Enantioselective Allene
Diboration and Intramolecular [2 + 2] Photocycloaddition for the
Construction of the Tricyclic Core. Chem. - Eur. J. 2016, 22, 1266−
1269.
(
d) Hu, P.; Snyder, S. A. Enantiospecific Total Synthesis of the Highly
Strained (−)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem
Cyclization. J. Am. Chem. Soc. 2017, 139, 5007−5010.
(
17) (a) Chen, M. S.; White, M. C. A Predictably Selective Aliphatic
C−H Oxidation Reaction for Complex Molecule Synthesis. Science
2007, 318, 783−787. (b) Bigi, M. A.; Reed, S. A.; White, M. C.
Directed Metal (Oxo) Aliphatic C−H Hydroxylations: Overriding
Substrate Bias. J. Am. Chem. Soc. 2012, 134, 9721−9726. (c) White,
M. C.; Zhao, J. Aliphatic C−H Oxidations for Late-Stage
Functionalization. J. Am. Chem. Soc. 2018, 140, 13988−14009.
(32) To optimize experimental convenience, formylation/reduction
was performed in lieu of quenching the alkyllithium reagent with
formaldehyde.
(
18) (a) Hung, K.; Condakes, M. L.; Morikawa, T.; Maimone, T. J.
Oxidative Entry Into the Illicium Sesquiterpenes: Enantiospecific
(33) Alternatively, the vinyl organometallic from iodide 15 was
Synthesis of (+)-Pseudoanisatin. J. Am. Chem. Soc. 2016, 138, 16616−
trapped efficiently with CO . Epoxidation of this highly conjested
2
1
6619. Maimone has also reported late stage oxidations in other
alkene was unsuccessful under a variety of conditions, including:
(a) Kirshenbaum, K. S.; Sharpless, K. B. Improved Procedure for the
Tungstate-Catalyzed Epoxidation of α,β-Unsaturated Acids. J. Org.
Chem. 1985, 50, 1979−1982. (b) Adam, W.; Hadjiarapoglou, L.;
Nestler, B. Dimethyldioxirane Epoxidation of α,β-Unsaturated
Ketones, Acids and Esters. Tetrahedron Lett. 1990, 31, 331−334.
(34) Several one-step oxidations were attempted, but none were
successful at generating the α-hydroxy acid, leading either to
decomposition or no reaction. Conditions investigated include
Jones oxidation, O /Pt, and TPAP/NMO/H O.
terpene syntheses: (b) Hung, K.; Condakes, M. L.; Novaes, L. F. T.;
Harwood, S. J.; Morikawa, T.; Yang, Z.; Maimone, T. J. Development
of a Terpene Feedstock-Based Oxidative Synthetic Approach to the
Illicium Sesquiterpenes. J. Am. Chem. Soc. 2019, 141, 3083−3099.
(
c) Condakes, M. L.; Hung, K.; Harwood, S. J.; Maimone, T. J. Total
Syntheses of (−)-Majucin and (−)-Jiadifenoxolane a, Complex
Majucin-Type Illicium Sesquiterpenes. J. Am. Chem. Soc. 2017, 139,
1
7783−17786.
19) Song, Z.-L.; Fan, C.-A.; Tu, Y.-Q. Semipinacol Rearrangement
in Natural Product Synthesis. Chem. Rev. 2011, 111, 7523−7556.
20) Dudev, T.; Lim, C. Ring Strain Energies From Ab Initio
Calculations. J. Am. Chem. Soc. 1998, 120, 4450−4458.
21) Details of these calculations can be found in the Supporting
Information.
22) Banwell, M. G.; Jury, J. C. Stereoselective Syntheses of the
(
2
2
(35) (a) Miller, T. C. Stereospecific D-Homoannulation of 17-
Hydroxy-3-Methoxyestra-1,3,5(10)-Triene-17-Alpha-Carboxaldehyde.
J. Org. Chem. 1969, 34, 3829−3833. (b) Creary, X.; Inocencio, P. A.;
Underiner, T. L.; Kostromin, R. Diels-Alder Approach to Bicyclic
Alpha-Hydroxy Ketones. Facile Ketol Rearrangements of Strained
Alpha-Hydroxy Ketones. J. Org. Chem. 1985, 50, 1932−1938.
(36) Ye, Q.; Qu, P.; Snyder, S. A. Total Syntheses of Scaparvins B,
C, and D Enabled by a Key C−H Functionalization. J. Am. Chem. Soc.
2017, 139, 18428−18431.
(
(
(
Methyl Esters of (E)- and (Z)-2-Methyl-6-Oxohept-2-eoic Acid. Org.
Prep. Proced. Int. 2004, 36, 87−91.
(
23) Boissarie, P.; Belanger, G. Short Approach Toward the
́
Nonracemic A,B,E Tricyclic Core of Calyciphylline B-Type Alkaloids.
(37) Bietti, M. Activation and Deactivation Strategies Promoted by
Medium Effects for Selective Aliphatic C−H Bond Functionalization.
Angew. Chem., Int. Ed. 2018, 57, 16618−16637.
Org. Lett. 2017, 19, 3739−3742.
(
24) It is unclear whether intermediate 12 is generated via α-
deprotonation or γ-deprotonation, and whether 1,5-hydride shifts are
operative under these conditions.
(38) To rationalize the selective oxidation of axial vs equatorial
hydrogens in cyclohexanes, relief of 1,3-diaxial strain in the transition
state has been proposed as an explanation. We reason that relief of the
trans-pentalene ring strain in the rate limiting transition state of the
C−H oxidation may similarly be a factor in our system. (a) Chen, K.;
Eschenmoser, A.; Baran, P. S. Strain Release in C−H Bond
Activation? Angew. Chem., Int. Ed. 2009, 48, 9705−9708. (b) New-
house, T.; Baran, P. S. If C−H Bonds Could Talk: Selective C−H
Bond Oxidation. Angew. Chem., Int. Ed. 2011, 50, 3362−3374.
(39) For example, see anislactone A and 7-debenzoyl-7-deoxo-
1α,7α-dihydroxytashironin: (a) Kouno, I.; Mori, K.; Okamoto, S.;
Sato, S. Structures of Anislactone A and B; Novel Type of
Sequiterpene Lactones From the Pericarps of Illicium Anisatum.
(
25) (a) Ryu, I.; Murai, S.; Shinonaga, A.; Horiike, T.; Sonoda, N.
Synthesis via Silyl Alkenyl Ethers. 14. Dimethyldicyanosilane: a
Reagent for Concurrent Silylation and Cyanosilylation of Beta-
Diketones. J. Org. Chem. 1978, 43, 780−782. (b) Singh Batra, M.;
Brunet, E. The Diastereoselective Preparation of Syn-Beta-Hydrox-
ycyanohydrins by Addition of Cyanide to Beta-Hydroxyketones with
Dimethyldicyanosilane. Tetrahedron Lett. 1993, 34, 711−714.
(
c) Dietz, W.; Schwerdtfeger, Y.; Klingebiel, U.; Noltemeyer, M.
Bis(1-Cyclohexen-3-on-1-Oxy)Silane, Silyl-Enole Von Β-Ketonen/
Bis (1-Cyclohexene-3-on-1-Oxy)Silanes, Silyl-Enoles of Β-Ketones. Z.
Naturforsch., B: J. Chem. Sci. 2007, 62, 1371−1376.
(
26) (a) Pine, S. H. Carbonyl Methylenation and Alkylidenation
Chem. Pharm. Bull. 1990, 38, 3060−3063. (b) Schmidt, T. J.; Muller,
̈
Using Titanium-Based Reagents. Org. React. 1993, 43, 1−90.
E.; Fronczek, F. R. New Allo-Cedrane Type Sesquiterpene Hemiketals
and Further Sesquiterpene Lactones From Fruits of Illicium
floridanum. J. Nat. Prod. 2001, 64, 411−414.
(
b) Johnson, C. R.; Tait, B. D. A Cerium(III) Modification of the
Peterson Reaction: Methylenation of Readily Enolizable Carbonyl
Compounds. J. Org. Chem. 1987, 52, 281−283.
(40) (a) Pirkle, W. H.; Hoekstra, M. S. Automated Liquid
Chromatography. Synthesis of a Broad-Spectrum Resolving Agent
and Resolution of 1-(1-Naphthyl)-2,2,2-Trifluoroethanol. J. Org.
(
27) (a) Corey, E. J.; Chaykovsky, M. Dimethylsulfoxonium
Methylide. J. Am. Chem. Soc. 1962, 84, 867−868. (b) Corey, E. J.;
E
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX