Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Construction of 1,3-Dithio-Substituted Tetralins by [1,5]-Alkylthio Group Transfer Mediated Skeletal Rearrangement Naoya Hisano,† Yuto Kamei,‡ Yaoki Kansaku,‡ Masahiro Yamanaka,*,‡ and Keiji Mori*,† †
Downloaded via TUFTS UNIV on June 29, 2018 at 20:15:59 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo 184-8588, Japan ‡ Department of Chemistry and Research Center for Smart Molecules, Rikkyo University, 3-34-1 Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan S Supporting Information *
ABSTRACT: A novel skeletal rearrangement involving a [1,5]-alkylthio group transfer/cyclization sequence is described. Treatment of benzylidene malonates having a thioketal moiety at the homobenzyl position with a catalytic amount of Sc(OTf)3 afforded alkylthio group rearranged adducts in good chemical yields. Detailed investigation of the reaction mechanism revealed that an intramolecular conjugate addition/ring opening sequence (not through-space transfer) is the key to achieving this reaction.
I
high feasibility of the transfer of other substituents besides hydrogen, which would open doors to novel skeletal rearrangements. In this context, the Alajarin and Vidal group found that the [1,4]-alkylthio group transfer was also a viable process (Scheme 2).8 Although their results were intriguing,
nterest in skeletal rearrangements has persisted for several decades.1 Skeletal rearrangements enable the construction of highly fused, complicated skeletons from relatively simple organic compounds. Besides their utility as synthetic methods, several features, such as (1) cleavage of relatively inert chemical bonds (e.g., C−C bond) and (2) formation of a different bond relative to the starting material, have fascinated synthetic organic chemists. Because of the useful features described above, the development of novel skeletal rearrangement reactions remains one of the most sought after topics in modern synthetic organic chemistry. Recently, our group has been interested in the development of hydride shift triggered C(sp3)−H bond functionalization, namely, the “internal redox reaction” (Scheme 1).2−7 The key
Scheme 2. Skeletal Rearrangement via Alkylthio Group Transfer/Cyclization Sequence
Scheme 1. C(sp3)−H Functionalization by Internal Redox Process
detailed investigation of both substrate scope and reaction mechanism of the transfer process was not conducted. Furthermore, the development of another mode of transfer process ([1,5]-transfer type reaction) is not a trivial issue because SR group is susceptible to the elimination due to the presence of benzylic hydrogens. Herein, we report our recent efforts toward the development of a novel skeletal rearrangement reaction involving a [1,5]alkylthio group transfer/cyclization sequence. Careful tuning of the reaction conditions revealed that the [1,5]-transfer of the
to achieving this reaction is the through-space [1,5]-hydride shift triggered by electronic assistance from the adjacent heteroatom (X). In the early stage, this method was limited to amino substrates having strong electron-donating ability. Recent efforts by our group5 as well as the Sames,7a−d Urabe,7e and Fillion groups4d revealed that both less reactive oxygen analogues (X = O) and carbon analogues without an adjacent heteroatom (X = CH2) were also good candidates for the transformation. The high tolerance to an electronic environment in the hydride shift process (X = N, O, CH2) strongly implies the © XXXX American Chemical Society
Received: May 22, 2018
A
DOI: 10.1021/acs.orglett.8b01610 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters alkylthio group occurred effectively, and corresponding adducts were obtained in good to excellent chemical yields under Sc(OTf)3 catalysis. Computational investigation of the reaction mechanism indicated that the [1,5]-alkylthio group transfer occurred intramolecularly and mostly proceeded via intramolecular conjugate addition/ring opening (not the through-space transfer) pathway. Table 1 illustrates the examination of the reaction conditions. When a solution of 3a in ClCH2CH2Cl was Table 1. Examination of Reaction Conditionsa
entry
catalyst
time (h)
1 2 3 4 5 6 7 8 9 10d 11e
Gd(OTf)3 Zn(OTf)2 Mg(OTf)2 Tf2NH Hf(OTf)4 Yb(OTf)3 TiCl4 Sc(OTf)3 Sc(OTf)3 Sc(OTf)3 Sc(OTf)3
48 48 48 48 48 48 4 48 24 48 48
yield (%) no reaction no reaction no reaction no reaction trace trace 50 88 76 (13)c 9 (86)c 75
drb
1.4:1 1.7:1 1:1.3 1:1.5 1:1.5 1:1.5 1:1.5
a
Unless otherwise noted, all reactions were conducted with 0.10 mmol of 3a in the presence of 10 mol % of catalyst in ClCH2CH2Cl (1.0 mL) at room temperature. bDiastereomeric ratio was determined by comparing the integration value of methine proton at the C-1 position for each diastereomer in the 1H NMR. cThe recovery of 3a is shown in parentheses. dIn toluene. e1.1 mmol scale.
Figure 1. Substrate scope.
treated with 10 mol % of Gd(OTf)3 at room temperature, the reaction did not proceed at all (entry 1). Compound 3a was recovered completely under Zn(OTf)2 and Mg(OTf)2 catalysis (entries 2 and 3). Use of a strong Brønsted acid (Tf2NH) was likewise ineffective (entry 4). A trace amount of the desired adduct 4a was obtained with low diastereoselectivity by using Hf(OTf)4 (dr = 1.4:1, entry 5).9 The same situation was noted when Yb(OTf)3 was employed as the catalyst (trace with dr = 1.7:1 at 50 °C, entry 6). Fortunately, TiCl4 promoted the desired reaction, and corresponding adduct 4a was obtained in 50% yield with 1:1.3 diastereomeric ratio (entry 7). Although the reaction was completed within 4 h, the chemical yield was difficult to improve by changing the reaction conditions (temperature, solvent, concentration, and so on). Further screening for the catalyst revealed that Sc(OTf)3 was effective for achieving excellent chemical yield, and corresponding adduct 4a was obtained in 88% yield with 1:1.5 diastereoselectivity (entry 8). Both prolonged reaction time (48 h) and employment of ClCH2CH2Cl were essential for achieving a satisfactory chemical yield, and the chemical yield of 4a was decreased under other conditions (entries 9 and 10).10 Importantly, this reaction could be performed on a 1.1 mmol scale with keeping both chemical yield and diastereomer ratio (entry 11). Figure 1 summarizes the substrate scope of this reaction. This reaction was applied to substrates 3b−f with electrondonating groups (Me and OMe) and an electron-withdrawing
group (F), and corresponding adducts 4b−f were obtained in good to excellent chemical yields (74−92%). Naphthyl-type product 4g was obtained in excellent chemical yield (99%). Terminal alkyl groups (R1) were also examined. Not only alkyl groups (Me, Et, Pr) but also phenyl groups afforded adducts 4a,h−j in moderate to good chemical yields. In particular, the reactivity of 3j (R1 = Ph) was extremely high, and the reaction was completed within 4 h (cf. 48 h for 4a). In sharp contrast, substrate 3k (R1 = H) derived from an aldehyde did not give adduct 4k at all. To our surprise, both S-transfer and hydride shift were not observed in the case of 3k, even though 3k had two electron-donating groups (SEt group). A substituent on an ester moiety had a negligible effect on the transformation, and 4l (R3 = Et) was obtained in 81% yield with increased catalyst loading (20 mol %). The employment of substrates with an acyclic alkylthio group was indispensable for the reaction: although SPr- and bulky SiPr-substituted products 4m and 4n were obtained in moderate to good chemical yields, 1,3-dithiane derivative 3o did not afford adduct 4o at all as reported by Alajarin and Vidal.8 To confirm the intramolecular nature of alkylthio group transfer process, crossover experiments with 3f and 3m were conducted (Scheme 3). The observation of only two products (4f and 4m) clearly indicates that key thio group transfer proceeds intramolecularly. B
DOI: 10.1021/acs.orglett.8b01610 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
planarity of the thiacarbenium moiety (Figure 3). These computational results are qualitatively consistent with the
Scheme 3. Crossover Experiments
On the basis of the above results, two reaction pathways could be assumed for the formation of key zwitterionic intermediate B (Scheme 4): (1) through-space transfer of SR Scheme 4. Two Possible Reaction Pathways Figure 3. 3D structures of TS1, TS2, and TS3. Bond lengths are in Å.
experimentally observed substituent effect on R1 and the substrate scope (Figure 1). The introduction of a Ph group on R1 (3j) would stabilize TS2 by conjugation with the generated thiacarbenium moiety, significantly accelerating the reaction rate. In contrast, cyclic 1,3-dithiane moiety (3o) needs to be considerably deformed for the C−S bond cleavage, significantly destabilizing TS2. The thiacarbenium intermediate INT2 directly connecting to TS3 is eventually formed through the sequential C1−C2/C2−C3/C4−C5 bond rotation. At this stage, such free bond rotation would occur with a low energy barrier, resulting in low diastereoselectivity (Figure S1). The relatively low energy barrier (3.6 kcal/mol) is attributed to the small structural distortion between INT2 and TS3 (Figure 3). In summary, we have developed a skeletal rearrangement reaction involving a [1,5]-alkylthio group transfer/cyclization sequence. Various substituents, such as electron-donating and electron-withdrawing groups on the aromatic ring, had a negligible effect on the reaction, and a wide variety of thio group transfer adducts were obtained in good to excellent chemical yields. Detailed investigation of the reaction mechanism based on theoretical calculations revealed that [1,5]-alkylthio group transfer occurred in the intramolecular conjugate addition/ring opening pathway unlike the case of the hydride shift process (through-space transfer), and ring opening of cyclic thionium was the rate-determining step. Further investigations of other group transfer/cyclization processes are under way in our laboratory, and the results will be reported in due course.
group (path 1) and (2) intramolecular conjugate addition to electrophilic vinylic carbon (cyclic thionium C formation) followed by ring opening (path 2). To gain a deeper insight into the mechanistic details, DFT calculations were conducted using a TiCl4-catalyzed reaction model (entry 7 in Table 1) to reduce computational cost.11 After exploring transition state (TS) structures on both reaction pathways, no TS was found along path 1 and path 2 was identified as the promising reaction pathway. Path 2 proceeds through a sequential mechanism: intramolecular conjugate addition (TS1), ring opening of cyclic thionium (TS2), and C−C bond formation (TS3), affording adduct 4 (Figure 2). The lower lying TS1 (+1.7 kcal/mol) indicates that the formation of cyclic thionium INT1 is a reversible process. TS2 located at the highest energy level (+12.2 kcal/mol) is identified as the rate-determining step. In TS2, the C−S bond cleavage is assisted by the C2−C3 bond rotation, enhancing the
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b01610. Experimental procedures, analytical and spectroscopic data for new compounds, computational details, Cartesian coordinates (PDF) 1 H and 13C NMR spectra (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
Figure 2. Gibbs free energy profile (in kcal/mol) of the intramolecular conjugate addition/ring opening process (path 2).
*E-mail:
[email protected]. C
DOI: 10.1021/acs.orglett.8b01610 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters *E-mail:
[email protected].
2010, 12, 1732. (c) Mori, K.; Sueoka, S.; Akiyama, T. J. Am. Chem. Soc. 2011, 133, 2424. (d) Mori, K.; Sueoka, S.; Akiyama, T. Chem. Lett. 2011, 40, 1386. (e) Mori, K.; Kawasaki, T.; Akiyama, T. Org. Lett. 2012, 14, 1436. (f) Mori, K.; Kurihara, K.; Akiyama, T. Chem. Commun. 2014, 50, 3729. (g) Mori, K.; Kurihara, K.; Yabe, S.; Yamanaka, M.; Akiyama, T. J. Am. Chem. Soc. 2014, 136, 3744. (h) Mori, K.; Umehara, N.; Akiyama, T. Adv. Synth. Catal. 2015, 357, 901. (i) Yoshida, T.; Mori, K. Chem. Commun. 2017, 53, 4319. For an asymmetric version of internal redox reaction catalyzed by chiral phosphoric acid, see: (j) Machida, M.; Mori, K. Chem. Lett. 2018, 47, 868. (k) Yokoo, K.; Mori, K. Chem. Commun. 2018, 54, 6927. Mori, K.; Umehara, N.; Akiyama, T. Chemical Science 2018, DOI: 10.1039/ C8SC02103A. (m) Mori, K.; Ehara, K.; Kurihara, K.; Akiyama, T. J. Am. Chem. Soc. 2011, 133, 6166. (n) Mori, K.; Isogai, R.; Kamei, Y.; Yamanaka, M.; Akiyama, T. J. Am. Chem. Soc. 2018, 140, 6203. (6) For examples of enantioselective internal redox reactions, see: (a) Murarka, S.; Deb, I.; Zhang, C.; Seidel, D. J. Am. Chem. Soc. 2009, 131, 13226. (b) Kang, Y. K.; Kim, S. M.; Kim, D. Y. J. Am. Chem. Soc. 2010, 132, 11847. (c) Cao, W.; Liu, X.; Wang, W.; Lin, L.; Feng, X. Org. Lett. 2011, 13, 600. (d) Zhou, G.; Liu, F.; Zhang, J. Chem. - Eur. J. 2011, 17, 3101. (e) He, Y.-P.; Du, Y.-L.; Luo, S.-W.; Gong, L. Z. Tetrahedron Lett. 2011, 52, 7064. (f) Chen, L.; Zhang, L.; Lv, Z.; Cheng, J.-P.; Luo, S. Chem. - Eur. J. 2012, 18, 8891. (g) Zhang, L.; Chen, L.; Lv, Z.; Cheng, J.-P.; Luo, S. Chem. - Asian J. 2012, 7, 2569. (h) Jiao, Z.-W.; Zhang, S.-Y.; He, C.; Tu, Y.-Q.; Wang, S.-H.; Zhang, F.-M.; Zhang, Y.-Q.; Li, H. Angew. Chem., Int. Ed. 2012, 51, 8811. (i) Kang, Y. K.; Kim, D. Y. Adv. Synth. Catal. 2013, 355, 3131. (j) Suh, C. W.; Woo, S. B.; Kim, D. Y. Asian J. Org. Chem. 2014, 3, 399. (k) Kang, Y. K.; Kim, D. Y. Chem. Commun. 2014, 50, 222. (l) Suh, C. W.; Kim, D. Y. Org. Lett. 2014, 16, 5374. (m) Yu, J.; Li, N.; Chen, D.-F.; Luo, S.-W. Tetrahedron Lett. 2014, 55, 2859. (n) Cao, W.; Liu, X.; Guo, J.; Lin, L.; Feng, X. Chem. - Eur. J. 2015, 21, 1632. See also ref 5m. (7) Internal redox reaction of oxygen analogue: (a) Pastine, S. J.; McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. 2005, 127, 12180. (b) Pastine, S. J.; Sames, D. Org. Lett. 2005, 7, 5429. (c) McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. 2009, 131, 402. (d) Vadola, P.; Sames, A. D. J. Am. Chem. Soc. 2009, 131, 16525. See also: (e) Shikanai, D.; Murase, H.; Hata, T.; Urabe, H. J. Am. Chem. Soc. 2009, 131, 3166. Also see refs 5b and 6h. (8) Alajarin, M.; Marin-Luna, M.; Vidal, A. Adv. Synth. Catal. 2011, 353, 557. (9) Ishitani, H.; Suzuki, H.; Saito, Y.; Yamashita, Y.; Kobayashi, S. Eur. J. Org. Chem. 2015, 5485. (10) The reaction with ketal 5 (not thioketal) under optimized reaction conditions afforded naphthalene 7 in 32% yield, which was produced by the following multistep sequence: activation of ketal moiety by Sc(OTf)3, deprotonative transformation to vinyl ether E, intramolecular conjugate addition reaction followed by tautomerization, and release of dimethyl malonate.
ORCID
Masahiro Yamanaka: 0000-0001-7978-620X Keiji Mori: 0000-0002-9878-993X Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS This work was partially supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and by grants from The Uehara Memorial Foundation, The Naito Foundation, and the Inoue Foundation of Science.
■
REFERENCES
(1) For recent reviews on skeletal rearrangements, see: (a) Shapiro, N. D.; Toste, F. D. Synlett 2010, 675. (b) Presset, M.; Coquerel, Y.; Rodriguez, J. Chem. Rev. 2013, 113, 525. (c) Obradors, C.; Echavarren, A. M. Acc. Chem. Res. 2014, 47, 902. (d) Le Bideau, F.; Kousara, M.; Chen, L.; Wei, L.; Dumas, F. Chem. Rev. 2017, 115, 6110. (e) Zhang, X.-M.; Tu, Y.-Tu; Zhang, F.-M.; Chen, Z.-H.; Wang, S.-H. Chem. Soc. Rev. 2017, 46, 2272. (2) For recent reviews on the internal redox process, see: (a) Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed. 2006, 45, 1683. (b) Pan, S. C. Beilstein J. Org. Chem. 2012, 8, 1374. (c) Wang, M. ChemCatChem 2013, 5, 1291. (d) Peng, B.; Maulide, N. Chem. - Eur. J. 2013, 19, 13274. (e) Wang, L.; Xiao, J. Adv. Synth. Catal. 2014, 356, 1137. (f) Haibach, M. C.; Seidel, D. Angew. Chem., Int. Ed. 2014, 53, 5010. (g) Kwon, S. J.; Kim, D. Y. Chem. Rec. 2016, 16, 1191. (3) These types of reactions are classified under the term “tert-amino effect”. For reviews, see: (a) Meth-Cohn, O.; Suschitzky, H. Adv. Heterocycl. Chem. 1972, 14, 211. (b) Verboom, W.; Reinhoudt, D. N. Recl. Trav. Chim. Pays-Bas 1990, 109, 311. (c) Meth-Cohn, O. Adv. Heterocycl. Chem. 1996, 65, 1. (d) Quintela, J. M. Recent Res. Dev. Org. Chem. 2003, 7, 259. (e) Matyus, P.; Elias, O.; Tapolcsanyi, P.; Polonka-Balint, A.; Halasz-Dajka, B. Synthesis 2006, 2625. (4) For selected examples of internal redox reactions, see: (a) Polonka-Bálint, A.; Saraceno, C.; Ludányi, K.; Bényei, A.; Mátyus, P. Synlett 2008, 2846. (b) Zhang, C.; Murarka, S.; Seidel, D. J. Org. Chem. 2009, 74, 419. (c) Ruble, J. C.; Hurd, A. R.; Johnson, T. A.; Sherry, D. A.; Barbachyn, M. R.; Toogood, P. L.; Bundy, G. L.; Graber, D. R.; Kamilar, G. M. J. Am. Chem. Soc. 2009, 131, 3991. (d) Mahoney, M. J.; Moon, D. T.; Hollinger, J.; Fillion, E. Tetrahedron Lett. 2009, 50, 4706. (e) Zhou, G.; Zhang, J. Chem. Commun. 2010, 46, 6593. (f) Cao, J.; Yang, X.; Hua, X.; Deng, Y.; Lai, G. Org. Lett. 2011, 13, 478. (g) Jurberg, I. D.; Peng, B.; Wöstefeld, E.; Wasserloos, M.; Maulide, N. Angew. Chem., Int. Ed. 2012, 51, 1950. (h) Sugiishi, T.; Nakamura, H. J. Am. Chem. Soc. 2012, 134, 2504. (i) Han, Y.-Y.; Han, W.-Y.; Zhang, X.-M.; Yuan, W.-C.; Hou, X. Org. Lett. 2012, 14, 4054. (j) Vadola, P. A.; Carrera, I.; Sames, D. J. Org. Chem. 2012, 77, 6689. (k) Gao, X.; Gaddam, V.; Altenhofer, E.; Tata, R. R.; Cai, Z.; Yongpruksa, N.; Garimallaprabhakaran, A. K.; Harmata, M. Angew. Chem., Int. Ed. 2012, 51, 7016. (l) Chen, D.-F.; Han, Z.-Y.; He, Y.-P.; Yu, J.; Gong, L.-Z. Angew. Chem., Int. Ed. 2012, 51, 12307. (m) Shaaban, S.; Maulide, N. Synlett 2013, 24, 1722. (n) Cera, G.; Chiarucci, M.; Dosi, F.; Bandini, M. Adv. Synth. Catal. 2013, 355, 2227. (o) Dieckmann, A.; Richers, M. T.; Platonova, A. Y.; Zhang, C.; Seidel, D.; Houk, N. K. J. Org. Chem. 2013, 78, 4132. (p) Alajarin, M.; Bonillo, B.; Marin-Luna, M.; Sanchez-Andrada, P.; Vidal, A. Chem. Eur. J. 2013, 19, 16093. (q) Vidal, A.; Marin-Luna, M.; Alajarin, M. Eur. J. Org. Chem. 2014, 2014, 878. (r) Chang, Y.-Z.; Li, M.-L.; Zhao, W.-F.; Wen, X.; Sun, H.; Xu, Q.-L. J. Org. Chem. 2015, 80, 9620. (s) Suh, C. W.; Kwon, S. J.; Kim, D. Y. Org. Lett. 2017, 19, 1334. (5) For the internal redox reaction developed by our group, see: (a) Mori, K.; Ohshima, Y.; Ehara, K.; Akiyama, T. Chem. Lett. 2009, 38, 524. (b) Mori, K.; Kawasaki, T.; Sueoka, S.; Akiyama, T. Org. Lett.
(11) Computational details are shown in the Supporting Information.
D
DOI: 10.1021/acs.orglett.8b01610 Org. Lett. XXXX, XXX, XXX−XXX
