Organic Letters
Letter
controlled 2-C- and 3-C-Allylation via Thermal Claisen Rearrange-
ment. J. Org. Chem. 1994, 59, 3427−3432.
(13) Direct C-alkylation of ascorbic acid has been studied: Poss, A. J.;
Belter, R. K. The C-Alkylation of Ascorbic Acid. Synth. Commun. 1988,
18, 417−423.
ACKNOWLEDGMENTS
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We thank Dr. Jacob C. DeForest for helpful discussions. The
University of California, Irvine supported this work.
(14) (a) Tsuji, J.; Takahashi, H.; Morikawa, M. Organic Syntheses by
Means of Noble Metal Compounds 0.17. Reaction of Pi-Allylpalladium
Chloride with Nucleophiles. Tetrahedron Lett. 1965, 6, 4387−4388.
(b) Trost, B. M.; Fullerton, T. J. New Synthetic Reactions. Allylic
Alkylation. J. Am. Chem. Soc. 1973, 95, 292−294.
(15) (a) Lu, Z.; Ma, S. Metal-Catalyzed Enantioselective Allylation in
Asymmetric Synthesis. Angew. Chem., Int. Ed. 2008, 47, 258−297.
(b) Trost, B. M.; Crawley, M. L. Asymmetric Transition-Metal-
Catalyzed Allylic Alkylations: Applications in Total Synthesis. Chem.
Rev. 2003, 103, 2921−2944.
(16) Morena-Manas, M.; Pleixats, R.; Villarroya, M. C-Allylation of L-
Ascorbic Acid Under Palladium(0) Catalysis. J. Org. Chem. 1990, 55,
4925−4928.
REFERENCES
■
(1) Block, E. Garlic and Other Alliums, The Lore and the Science; The
Royal Society of Chemistry: Cambridge, UK, 2010.
(2) Cavallito, C. J.; Bailey, J. H. Allicin, the Antibacterial Principle of
Allium Sativum. I. Isolation, Physical Properties and Antibacterial
Action. J. Am. Chem. Soc. 1944, 66, 1950−1951.
(3) El-Aasr, M.; Fujiwara, Y.; Takeya, M.; Ikeda, T.; Tsukamoto, S.;
Ono, M.; Nakano, D.; Okawa, M.; Kinjo, J.; Yoshimitsu, H.; Nohara, T.
Onionin A from Allium cepa Inhibits Macrophage Activation. J. Nat.
Prod. 2010, 73, 1306−1308.
(4) Keiss, H. P.; Dirsch, V. M.; Hartung, T.; Haffner, T.; Trueman, L.;
Auger, J.; Kahane, R.; Vollmar, A. M. Garlic (Allium sativum L.)
Modulates Cytokine Expression in Lipopolysaccharide-Activated
Human Blood Thereby Inhibiting NF-Kappa B Activity. J. Nutr.
2003, 133, 2171−2175.
(5) Block, E. The Organosulfur Chemistry of the Genus Allium -
Implications for the Organic-Chemistry of Sulfur. Angew. Chem., Int. Ed.
Engl. 1992, 31, 1135−1178.
(6) Fukaya, M.; Nakamura, S.; Nakagawa, R.; Nakashima, S.;
Yamashita, M.; Matsuda, H. Rare Sulfur-Containing Compounds,
Kujounins A1 and A2 and Allium Sulfoxide A1, from Allium Fistulosum
“Kujou. Org. Lett. 2018, 20, 28−31.
(7) Zhao, J.-X.; Yu, Y.-Y.; Wang, S.-S.; Huang, S.-L.; Shen, Y.; Gao, X.-
H.; Sheng, L.; Li, J.-Y.; Leng, Y.; Li, J.; Yue, J.-M. Structural Elucidation
and Bioinspired Total Syntheses of Ascorbylated Diterpenoid
Hongkonoids A−D. J. Am. Chem. Soc. 2018, 140, 2485−2492.
(8) (a) Imai, S.; Tsuge, N.; Tomotake, M.; Nagatome, Y.; Sawada, H.;
Nagata, T.; Kumagai, H. An Onion Enzyme That Makes the Eyes Water
- a Flavoursome, User-Friendly Bulb Would Give No Cause for Tears
When Chopped Up. Nature 2002, 419, 685−685. (b) Thomson, S. J.;
Rippon, P.; Butts, C.; Olsen, S.; Shaw, M.; Joyce, N. I.; Eady, C. C.
Inhibition of Platelet Activation by Lachrymatory Factor Synthase
(LFS)-Silenced (Tearless) Onion Juice. J. Agric. Food Chem. 2013, 61,
10574−10581.
(9) Lawson, L. D.; Hughes, B. G. Characterization of the Formation of
Allicin and Other Thiosulfinates from Garlic. Planta Med. 1992, 58,
345−350.
(10) Block, E.; Dane, A. J.; Thomas, S.; Cody, R. B. Applications of
Direct Analysis in Real Time Mass Spectrometry (DART-MS) in
Allium Chemistry. 2-Propenesulfenic and 2-Propenesulfinic Acids,
Diallyl Trisulfane S-Oxide, and Other Reactive Sulfur Compounds from
Crushed Garlic and Other Alliums. J. Agric. Food Chem. 2010, 58,
4617−4625.
(11) S−O zwitterions are known to accelerate [3,3] sigmatropic
rearrangements: (a) Block, E.; Ahmad, S. Unusually Facile Thio-
Claisen Rearrangement of 1-Alkenyl 2-Alkenyl Sulfoxides: a New
Sulfine Synthesis. J. Am. Chem. Soc. 1985, 107, 6731−6732. (b) Block,
E.; Bayer, T.; Naganathan, S.; Zhao, S.-H. AlliumChemistry: Synthesis
and Sigmatropic Rearrangements of Alk(en)yl 1-Propenyl Disulfide S-
Oxides From Cut Onion and Garlic. J. Am. Chem. Soc. 1996, 118,
2799−2810. (c) Hwu, J. R.; Anderson, D. A. The Zwitterion-
Accelerated [3,3]-Sigmatropic Rearrangement of Allyl Vinyl Sulfoxides
to Sulfines - a Specific Class of Charge-Accelerated Rearrangement.
Tetrahedron Lett. 1986, 27, 4965−4968. (d) Hwu, J. R.; Anderson, D. A.
Zwitterion-Accelerated [3,3]-Sigmatropic Rearrangements and [2,3]-
Sigmatropic Rearrangements of Sulfoxides and Amine Oxides. J. Chem.
Soc., Perkin Trans. 1 1991, 3199−3206.
(12) (a) Olabisi, A. O.; Mahindaratne, M. P. D.; Wimalasena, K. A
Convenient Entry to C2- and C3-Substituted Gulono-γ-Lactone
Derivatives From L-Ascorbic Acid. J. Org. Chem. 2005, 70, 6782−
6789. (b) Olabisi, A. O.; Wimalasena, K. Rational Approach to Selective
and Direct 2-O-Alkylation of 5,6-O-Isopropylidine-L-Ascorbic Acid. J.
Org. Chem. 2004, 69, 7026−7032. (c) Wimalasena, K.; Mahindaratne,
M. P. D. Chemistry of L-Ascorbic Acid: Regioselective and Stereo-
(17) (a) Kazmaier, U.; Zumpe, F. L. Chelated Enolates of Amino Acid
EstersEfficient Nucleophiles in Palladium-Catalyzed Allylic Sub-
stitutions. Angew. Chem., Int. Ed. 1999, 38, 1468−1470. (b) Kazmaier,
U.; Zumpe, F. L. Palladium-Catalyzed Allylic Alkylations Without
Isomerization - Dream or Reality? Angew. Chem., Int. Ed. 2000, 39,
802−804. (c) Kazmaier, U.; Zumpe, F. L. Chelated Enolates of Amino
Acid Esters - New and Efficient Nucleophiles for Isomerization-Free,
Stereoselective Palladium-Catalyzed Allylic Substitutions. Eur. J. Org.
Chem. 2001, 2001, 4067−4076.
(18) (a) Trost, B. M.; Verhoeven, T. R. Allylic Substitutions with
Retention of Stereochemistry. J. Org. Chem. 1976, 41, 3215−3216.
(b) Trost, B. M.; Verhoeven, T. R. New Synthetic Reactions. Catalytic
vs. Stoichiometric Allylic Alkylation. Stereocontrolled Approach to
Steroid Side Chain. J. Am. Chem. Soc. 1976, 98, 630−632.
(19) Assignments of the anomeric isomers of 26 were made by NMR
analysis and computational modeling using the DP4+ method. Details
are provided in the SI. DP4+ method: Grimblat, N.; Zanardi, M. M.;
Sarotti, A. M. Beyond DP4: an Improved Probability for the
Stereochemical Assignment of Isomeric Compounds Using Quantum
Chemical Calculations of NMR Shifts. J. Org. Chem. 2015, 80, 12526−
12534.
(20) (a) Davis, B. G.; Maughan, M.; Green, M. P.; Ullman, A.; Jones, J.
B. Glycomethanethiosulfonates: Powerful Reagents for Protein
Glycosylation. Tetrahedron: Asymmetry 2000, 11, 245−262. (b) Ber-
glund, P.; DeSantis, G.; Stabile, M. R.; Shang, X.; Gold, M.; Bott, R. R.;
Graycar, T. P.; Lau, T. H.; Mitchinson, C.; Jones, J. B. Chemical
Modification of Cysteine Mutants of Subtilisin Bacillus lentus Can
Create Better Catalysts Than the Wild-Type Enzyme. J. Am. Chem. Soc.
1997, 119, 5265−5266. (c) Matsumoto, K.; Davis, B. G.; Jones, J. B.
Chemically Modified “Polar Patch” Mutants of Subtilisin in Peptide
Synthesis with Remarkably Broad Substrate Acceptance: Designing
Combinatorial Biocatalysts. Chem. - Eur. J. 2002, 8, 4129−4137.
(d) Taniguchi, N. Unsymmetrical Disulfide and Sulfenamide Synthesis
via Reactions of Thiosulfonates with Thiols or Amines. Tetrahedron
2017, 73, 2030−2035.
(21) Examples using reagent PhSO2SNa: (a) Goddard-Borger, E. D.;
Stick, R. V. The Synthesis of Various 1,6-Disulfide-Bridged D-
Hexopyranoses. Aust. J. Chem. 2005, 58, 188−198. (b) Gamblin, D.
P.; Garnier, P.; Ward, S. J.; Oldham, N. J.; Fairbanks, A. J.; Davis, B. G.
Glycosyl Phenylthiosulfonates (Glyco-PTS): Novel Reagents for
Glycoprotein Synthesis. Org. Biomol. Chem. 2003, 1, 3642−3644.
(22) La(OTf)3 hydrolysis: DeLorbe, J. E.; Horne, D.; Jove, R.;
Mennen, S. M.; Nam, S.; Zhang, F.-L.; Overman, L. E. General
Approach for Preparing Epidithiodioxopiperazines From Trioxopiper-
azine Precursors: Enantioselective Total Syntheses of (+)- and
(−)-Gliocladine C, (+)-Leptosin D, (+)-T988C, (+)-Bionectin a,
and (+)-Gliocladin A. J. Am. Chem. Soc. 2013, 135, 4117−4128.
D
Org. Lett. XXXX, XXX, XXX−XXX