factors for the intermediate phenoxenium cation formed during
an oxidative dearomatization process mediated by hypervalent
We acknowledge the financial support provided by the
Department of Science and Technology [(DST), SB/FT/CS-
073/2013], New Delhi, India.
1
4
iodine(III) ragents. Thus, the higher yields in TFE and HFIP
compared to that in acetonitrile were not surprising.
Nevertheless, this transformation was best carried out using
PIDA as an oxidizing agent and K CO as a base in HFIP (entry
Supplementary Material
2
3
1
5
). It is important to mention that Boc group was not affected by
Experimental procedures, characterization data and copies of H
1
3
HFIP which has been reported to cause Boc deprotection, albeit
under much harsher reaction conditions (compared to the
and C NMR spectra for final compounds are available.
1
5
conditions described in Table 1).
References and notes
1
.
(a) Hughes, A. B., Ed: Amino Acids, Peptides and Proteins in
Organic Chemistry; Wiley-VCH: Weinheim, Germany, 2009;
Vols. 1 and 2; (b) Walsh, C. T.; O’Brien, R. V.; Khosla, C.
Angew. Chem., Int. Ed. 2013, 52, 7098–7124; (c) Fischbach, M.
A.; Walsh, C. T. Chem. Rev. 2006, 106, 3468–3496; (d) Walsh, C.
T. Science 2004, 303, 1805–1810; (e) Marahiel, M. A.;
Stachelhaus, T.; Mootz, H. D. Chem. Rev. 1997, 97, 2651–2674;
Table 1. Screening of reaction conditions on the oxidative
a
dearomatization ─ regioselective spirocyclization of 6a,b
(f) Fenteany, G.; Standaert, R. F.; Lane, W. S.; Choi, S.; Corey, E.
J.; Schreiber, S. L. Science 1995, 268, 726–731.
2
.
(a) Soloshonok, V. A.; Izawa, K. Asymmetric synthesis and
application of -amino acids; Oxford University Press:
Washington, DC, 2009; (b) Blaskovich, M. A. Handbook on
syntheses of amino acids: general routes for the syntheses of
amino acids; Oxford University Press: Oxford, New York, 2010.
Katagiri, K.; Tori, K.; Kimura, Y.; Yoshida, T.; Nagasaki, T.;
Minato, H. J. Med. Chem. 1967, 10, 1149−1154.
Kohno, T.; Kohda, D.; Haruki, M.; Yokoyama, S.; Miyazawa, T.
J. Biol. Chem. 1990, 265, 6931−6935.
Jung, J.-H.; Yoon, D.-H.; Lee, K.; Shin, H.; Lee, W. K.; Yook,
C.-M.; Ha, H.-J. Org. Biomol. Chem. 2015, 13, 8187–8195 and
references cited therein.
a
a
entry
1
conditions
yield
3
4
5
.
.
.
PIDA, K CO , MeCN
27% (5a); 36% (5b)
29% (5a); 35% (5b)
52% (5a); 55% (5b)
55% (5a); 59% (5b)
65% (5a); 62% (5b)
57% (5a); 58% (5b)
2
3
2
3
4
5
6
PIFA, pyridine, MeCN
PIDA, K CO , TFE
2
3
6
7
8
.
.
.
For selected examples, see: (a) Gravel, E.; Poupon, E. Nat. Prod.
Rep. 2010, 27, 32–56; (b) Cai, Y.-S.; Guo, Y.-W.; Krohn, K. Nat.
Prod. Rep. 2010, 27, 1840–1870; (c) Jin, Z. Nat. Prod. Rep. 2005,
PIFA, pyridine, TFE
PIDA, K CO , HFIP
2
2, 111–126; (d) Antunes, E. M.; Copp, B. R.; Davies-Coleman,
M. T.; Samaai, T. Nat. Prod. Rep. 2005, 22, 62–72; (e)
Venkatesan, H.; Davis, M. C.; Altas, Y.; Snyder, J. P.; Liotta, D.
C. J. Org. Chem. 2001, 66, 3653–3661.
2
3
For the importance of spiro-fused cyclohexadienone
─
PIFA, K CO , HFIP
tetrahydrofuran (SFCT) system, see: a) Heilmann, J.; Mayr , S.;
Brun , R.; Rali , T.; Sticher , O. Helv. Chim. Acta 2000, 83, 2939–
2
3
2
945; (b) Chin, Y.-W.; Salim, A. A.; Su, B.-N.; Mi, Q.; Chai, H.-
a
Reaction conditions: 6a or 6b (0.1 mmol), K
2
CO
3
(0.12 mmol) or pyridine
B.; Riswan, S.; Kardono, L. B. S.; Ruskandi, A.; Farnsworth, N.
R.; Swanson, S. M.; Kinghorn, A. D. J. Nat. Prod. 2008, 71, 390–
(
0.2 mL), solvent (2 mL) at 0 °C – rt for 15 min (for entries 1 and 2) or 10
min (for entries 3-6) . Isolated yields after column chromatography.
b
3
95.
For the selected recent synthesis of spiro-fused cyclohexadienone
tetrahydrofuran (SFCT) system, see: (a) Chandrasekhar, S.;
Rambabu, Ch.; Shyamsunder, T. Tetrahedron Lett. 2007, 48,
683–4685; (b) Ramana, C. V.; Srinivas, B.; Puranik, V. G.;
─
Notably, the oxidative dearomatization ─ spirocyclization was
completely regioselective as we could not find even any trace of
the corresponding spiro-fused cyclohexadienone ─ piperidine
ring system which might arise due to the nucleophilic attack of
the NHBoc group (instead of the –OH group). The synthesis
involves a total of 12 linear steps for each of 5a and 5b. Further
diversification (ring size and substituents) of this methodology
along with its relevant synthetic and medicinal applications is
underway in our laboratory and will be reported in due course as
a full paper.
4
Gurjar, M. K. J. Org. Chem. 2005, 70, 8216–8219; (c) Peuchmaur,
M.; Saıdani, N.; Botté, C.; Maréchal, E.; Vial, H.; Wong, Y. S. J.
Med. Chem. 2008, 51, 4870–4873; (d) Cha, J. Y.; Huang, Y.;
Pettus, T. R. R. Angew. Chem., Int. Ed. 2009, 48, 9519–9521; (e)
Malathong, V.; Rychnovsky, S. D. Org. Lett. 2009, 11, 4220–
4
1
223; (f) Yao, H.; Song, L.; Tong, R. J. Org. Chem. 2014, 79,
498–1504; (g) Reddy, R. R.; Gudup, S. S.; Ghorai, P. Angew.
Chem., Int. Ed. 2016, 55, 15115–15119.
9
1
.
(a) Borgohain, H.; Devi, R.; Dheer, D.; Borah, B. J.; Shankar, R.;
Das, S. K. Euro. J. Org. Chem. 2017, 6671–6679; (b) Das, S. K.
Asian J. Org. Chem. 2017, 6, 243–256; (c) Devi, R.; Das, S. K.
Beilstein J. Org. Chem. 2017, 13, 571–578; (d) Gogoi, D.; Devi,
R.; Pahari, P.; Das, S. K. Beilstein J. Org. Chem. 2016, 12, 2816–
2822; (e) Devi, R.; Gogoi, D.; Bora, P.; Das, S. K. Tetrahedron
In summary, we have described our preliminary efforts toward
the synthesis of spiro-fused cyclohexadienone ─ tetrahydrofuran
containing glycine derivatives for which we chose Sharpless
asymmetric dihydroxylation as the source of chirality and PIDA-
2
2
016, 72, 4878-4888; (f) Devi, R.; Kalita, T.; Das, S. K. RSC Adv.
015, 5, 39692–39696.
mediated
oxidative
dearomatization
─
regioselective
0. Fleming, P. R.; Sharpless, K. B. J. Org. Chem. 1991, 56, 2869–
875.
spirocyclization as the key step. Owing to the ease with which
the starting materials for the oxidative dearomatization-
spirocyclization could be made, as well as the high
derivatizability of a spirocyclohexadienone moiety, this synthetic
route should be useful as a general route to wide varieties of
related unnatural -amino acid derivatives.
2
11. The ee values of 7a,b were determined by chiral HPLC analysis.
See Supporting Information for details.
1
1
1
2. (a) Zhdankin, V. V. ARKIVOC 2009, 1, 1–62; (b) Yoshimura, A..;
Zhdankin, V. V. Chem. Rev. 2016, 116, 3328–3435.
3. Khaksar, S.; Heydari, A.; Tajbakhsh, M.; Vahdat, S. M. J.
Fluorine Chem. 2010, 131, 1377–1381.
4. (a) Kita, Y.; Tohma, H.; Kikuchi, K.; Inagaki, M.; Yakura, T. J.
Org. Chem. 1991, 56,435–438; (b) Kita, Y.; Tohma, H.; Hatanaka,
Acknowledgments