Subscriber access provided by BOSTON UNIV
Communication
Enantioselective Total Synthesis of (-)Caldaphnidine O via a Radical Cyclization Cascade Lian-Dong Guo, Jingping Hu, Yan Zhang, Wentong Tu, Yue Zhang, Fan Pu, and Jing Xu J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b07558 • Publication Date (Web): 05 Aug 2019 Downloaded from pubs.acs.org on August 5, 2019
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Journal of the American Chemical Society
Enantioselective Total Synthesis of (−)-Caldaphnidine O via a Radical Cyclization Cascade Lian-Dong Guo, Jingping Hu,† Yan Zhang,† Wentong Tu,† Yue Zhang, Fan Pu and Jing Xu* Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology, Shenzhen, China.
Supporting Information Placeholder ABSTRACT: The synthetically challenging, diverse chemical skeletons and promising biological profiles of the Daphniphyllum alkaloids have generated intense interest from the synthetic chemistry community. Herein, the first and enantioselective total synthesis of (−)-caldaphnidine O, a complex bukittinggine-type Daphniphyllum alkaloid, is described. The key transformations in this concise approach included an intramolecular aza-Michael addition, a ring expansion reaction sequence, a Sm(II)/Fe(III)mediated Kagan-Molander coupling, and the rapid formation of the entire hexacyclic ring skeleton of the target molecule via a radical cyclization cascade reaction, which was inspired by an unexpected radical detosylation observed in our recent dapholdhamine B synthesis.
Scheme 1. Heathcock's Landmark Total Synthesis of (±)Bukittinggine and the Chemical Structures of Representative Bukittinggine-type Alkaloids OBn H N
OBn Biomimetic Diels-Alder/ Aza-Prins cascade R
Ref. 4a and 4g BnO
N H R = OBn
CO2Me
CO2Me
O O
The Daphniphyllum alkaloids are a family of structurally complicated natural products that have long attracted intense attention from the synthetic chemistry community.1,2 In addition to their intriguing polycyclic ring system, these alkaloids exhibit promising bioactivities that range from cytotoxic and anticarcinogenic to neurotrophic and anti-HIV activities.3 Ever since Heathcock’s inaugural total synthesis of several Daphniphyllum alkaloids using elegant, biomimetic approaches,4 more than twenty impressive total synthesis of Daphniphyllum alkaloids have been accomplished by eleven research groups, namely, the Carreira,5 Smith,6 Li,7 Hanessian,8 Fukuyama,9 Zhai,10 Dixon,11 Qiu,12 ourselves,13 Gao14 and Sarpong15 groups. To date, the only known synthesis of a bukittinggine-type alkaloid, bukittinggine, was reported by the Heathcock group in 1992, which featured a remarkable biomimetic Diels-Alder/aza-Prins reaction cascade (Scheme 1).4a,g From a synthetic strategy perspective, a non-biomimetic yet equally efficient cyclization cascade would be an important addition to the synthesis of Daphniphyllum alkaloids. Herein, we report the first and enantioselective total synthesis of the bukittinggine-type alkaloid (−)-caldaphnidine O via a highly efficient radical cyclization cascade. Recently, we accomplished the first and enantioselective total synthesis of dapholdhamine B.13b During this fascinating journey, an unexpected but interesting detosylation reaction was observed (Scheme 2). When S-methyl xanthate 1 was subjected to a BartonMcCombie deoxygenation reaction, imine 3 was afforded as the detosylated product. On the basis of Curran’s pioneering findings,16 it was postulated that the secondary alkyl radical generated in the Barton-McCombie deoxygenation reaction underwent a 1,5-hydrogen atom transfer (HAT), thus triggering the subsequent radical detosylation. Moreover, imine 3 could be
N H Caldaphnidine O
N HO Caldaphnidine P
N H Bukittinggine
further reduced to secondary amine 4. Inspired by this key observation, a radical cyclization cascade reaction was designed for the total synthesis of the bukittinggine-type Daphniphyllum alkaloids, such as (−)-caldaphnidine O. (−)-Caldaphnidine O is a unique hexacyclic alkaloid which was isolated and identified in 2008 by Yue et al.17 The complicated architecture of (−)caldaphnidine O contains nine contiguous stereocenters and three quaternary centers, which makes its chemical synthesis a remarkable challenge. The retrosynthetic analysis of (−)caldaphnidine O indicated that the hexacyclic ring system of the target molecule could be efficiently achieved via a radical cyclization cascade reaction using dienyne substrate 5 (Scheme 2). It was envisaged that an enyne radical cyclization would form the C18-C2 bond of the target molecule, and concurrently trigger the critical 1,5-HAT to create an -aminyl radical at C-7 position. Subsequent radical trapping by the C9-C10 alkene would afford the key C7-C10 bond, thus furnishing the entire ring skeleton of the bukittinggine-type alkaloid. Next, it was assumed that the cyclopentene motif of 5 could be converted from the alkyl iodide 6 via a Kagan-Molander coupling reaction.18 The sevenmembered ring of compound 6 could be assembled from a ring expansion reaction sequence. Finally, we envisioned that the C1-N bond formation could be achieved via an intramolecular azaMichael addition (IMAM) from sulfonylamide diketone 7, a readily available chiral starting material.13b
ACS Paragon Plus Environment
Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Scheme 2. Key Inspiration and the Retrosynthetic Analysis of the Bukittinggine-type Alkaloid (−)-Caldaphnidine O Key Inspiration: An unexpected detosylation triggered by a Barton-McCombie deoxygenation OBn
OBn OTf nBu3SnH, AIBN
O S
OTf Ts N H H H 2
Barton-McCombie deoxygenation S
N Ts 1
1,5-HAT and detosylation OBn
OBn OTf
OTf
NaBH(OAc)3 90% N
HN 4
3
Retrosynthetic analysis of the bukittinggine-type alkaloid ()-caldaphnidine O OH
CO2Me Radical cyclization cascade
2 9
18
N
N 7
H ()-Caldaphnidine O
10
H 5
Sm(II)/Fe(III)-mediated Kagan-Molander coupling OBn O
BnO IMAM & Ring expansion
I O
Page 2 of 6
required. Introducing the homoallylic nucleophile to the ketone moiety was unexpectedly difficult. Using homoallyl magnesium bromide resulted in no reaction even with an excess amout of the Grignard reagent and elevated temperatures. Homoallyl lithium gave only poor yield of diol 11 (ca. 30%). Gratifyingly, treating -hydroxyl ketone 10 with a homoallyl cerium reagent,22 which was generated in situ by mixing homoallyl magnesium bromide with CeCl3, quantitatively produced diol 11. The C-9 stereoconfiguration in diol 11 was inconsequential because the following transformation generated an sp² hybridized center at the C-9 position. Oxidative cleavage of the diol moiety in compound 11, followed by selective reduction of the aldehyde group effectively yielded primary alcohol 12. Inspired by Smith’s impressive synthesis of (−)-calyciphylline N,6 primary alcohol 12 was converted into the corresponding alkyl iodide, which was then subjected to LDA conditions (2 equiv.) to afford compounds 13a and 13b, with the desired seven-membered ring moiety, as C10 diastereomers (13a:13b = 2:1). Notably, this alkylation did not occur if the reaction temperature was lower than −50 ℃, while the starting materials underwent decomposition if the reaction temperature was higher than 0 ℃. Pleasingly, both of the C-10 diastereomers, 13a and 13b, could be converted into the radical cyclization precursor 15 in three steps. The terminal alkene in compound 13a was converted into the corresponding alkyl iodide using 9-BBN/NaOMe/I2 conditions.23 Treating this alkyl iodide using Molander’s conditions (SmI2, Fe(dbm)3)18b-d smoothly furnished cyclopentanol 14a in 68% yield (two steps). Interestingly, this Kagan-Molander coupling did not occur when SmI2 was used without the presence of Fe(dbm)3. Moreover, only a trace amount of compound 14a was observed when HMPA was used instead of Fe(dbm)3; use of HMPA produced mainly the dehalogenated alkane product. Knochel’s protocol24 was also attempted, but this trial gave similar results to using the SmI2/HMPA conditions. Under Molander’s conditions, compound 13b was also converted into cyclopentanol 14b in two steps (75% yield). The stereoconfigurations of compounds 14a and 14b were unambiguously confirmed via single crystal X-ray diffraction.25
Table 1. Optimization of the dehydration reaction
1
O
OBn
OBn
OBn
Ts
N H 7, Readily available chiral starting material
N Ts
6
As outlined in Scheme 3, our synthesis commenced with the known chiral synthon 7 (94% ee), which was converted from 1,3cyclohexanedione 8 in seven steps and 16% overall yield.13b,19 Notably, attempts of converting 1,3-cycloheptanedione into the 6/7 bicyclic analogue of 7 was not successful, owing to the failed construction of the adjacent quaternary center via Luche’s conjugate addition.2o,13,20 Treating sulfonylamide diketone 7 with KHMDS/PhNTf2 conditions, followed by addition of an extra equivalent of KHMDS and Davis oxaziridine, triggered the desired IMAM reaction as well as the -hydroxylation reaction in the same pot to afford tricyclic compound 9 as a single diastereomer. The stereoconfiguration of the -hydroxyl group, albeit inconsequential, was assigned as the -configuration as the -hydroxylation was assumed to occur from the convex face of the cage-like substrate. A Pd(0)-mediated reduction21 of the enol triflate motif in compound 9 produced alkene 10. At this stage, expansion of the six-membered ring, bearing the -hydroxyl ketone motif, to the corresponding seven-membered ring was
OH
Ts
8
or
N
Ts 14a
OH
conditions
N
Ts 14b
N 15
entrya
compound
conditions
15 (%)b
1
14a
p-TsOH, PhMe, 90 °C, 3 h
35
2
14b
p-TsOH, PhMe, 90 °C, 1 h
20 c
3
14a
SOCl2, Py, 0 °C to r.t., 1 h
62
4d
14a
SOCl2, Py, 0 °C to r.t., 1 h
55
5
14b
SOCl2, Py, 0 °C to r.t., 1 h
trace c
6
14a
Burgess reagent, CH3CN, 70 °C, 1.5 h
trace c
7
14b
Burgess reagent, CH3CN, 70 °C, 1.5 h
57
8
14b
Burgess reagent, CH3CN, 70 °C, 1.5 h
60
d
a0.05
mmol scale. bIsolated yield. cMost of the starting material was decomposed. d1.4 mmol scale.
ACS Paragon Plus Environment
Page 3 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Journal of the American Chemical Society Scheme 3. Enantioselective Total Synthesis of (−)-Caldaphnidine O via a Radical Cyclization Cascade OBn
OBn O
ref. 13b
KHMDS, Davis oxaziridine, 68%
O Ts
8
N H 7, 94% ee
O OH
1) KHMDS, PhNTf2;
7 steps, 16% O
OBn O
O
HCOOH, DIPEA 88%
TfO Ts
N
Ts
MgBr , CeCl3
OBn
O 10
6) I2, PPh3, Im 7) LDA
10
+ N Ts
Ts
OH
N Ts
+
11
OBn
OH
OH
10) SOCl2, Py, 55% (from 14a)
2
11) Na-Naph., DME; 18
N
14b, 75% for 2 steps
Ts
N
12
OBn
N
Ts
EtOH, propargyl bromide 66%
N
N 7
10
H
15
14a, 68% for 2 steps
OH OH
75% for 3 steps
OH
8) 9-BBN; NaOMe, I2 9) SmI2, Fe(dbm)3
8) 9-BBN; NaOMe, I2 9) SmI2, Fe(dbm)3
9
67% for 2 steps
N
13a, 45%
OBn
OBn
4) Pb(OAc)4 5) NaBH4 O
13b, 22%
Ts
10
OBn O
Ts
N
9, single diastereomer 3)
OBn
OH
2) Pd(OAc)2, PPh3
5
10) Burgess reagent, 60% (from 14b)
S
O
S
OEt
P
OEt
12) nBu3SnH, AIBN; p-TsOH, 68%
17
CO2Me
CO2Me
13) Swern [O]
15) H2, Pt/C N (14a, XRD)
(14b, XRD)
()-Caldaphnidine O
70% for the desired diastereomer (dr = 4:1)
At this stage, elimination of the tertiary hydroxyl group in compounds 14a and 14b was required to furnish cyclopentene 15 (Table 1). Various dehydration conditions were investigated. When treating compounds 14a or 14b with p-TsOH, the desired product, cyclopentene 15, was isolated in 35% and 20% yield, respectively (Table 1, entries 1 and 2). Gratifyingly, subjecting compound 14a to SOCl2/pyridine conditions produced alkene 15 in a much improved yield (Table 1, entries 3 and 4), while under the same conditions, only poor results were observed for compound 14b (Table 1, entry 5). Conversely, treating substrate 14a with Burgess reagent produced only a trace amount of desired cyclopentene 15 (Table 1, entry 6), while using Burgess reagent effectively converted compound 14b into compound 15 in 57%– 60% yield (Table 1, entries 7 and 8). For substrate 14b, it is postulated that the more common syn-elimination process, under Burgess conditions, was unfavored, owing to the severe steric hindrance at the C-8 quaternary center.26 Next, the concurrent removal of the N-tosyl group, as well as the O-benzyl group, using sodium naphthalenide, followed by an N-propargylation reaction in the same pot, smoothly converted sulfonylamide 15 into the key radical cyclization precursor
OH
N 18
14) nBuLi, 17; p-TsOH; then NaOMe 70% for 2 steps
N 16
dienyne 5. Notably, an additional base, such as K2CO3, which is commonly used in the N-propargylation reaction, was not required in this one-pot N-detosylation/N-propargylation reaction, as addition of ethanol to the reaction mixture, that contained an excess amount of sodium naphthalenide, produced a sufficient amount of sodium ethoxide, thus allowing the N-propargylation reaction to occur. Successful preparation of a sufficient amount of dienyne 5 finally set the stage for the key radical cyclization cascade reaction. To our delight, subjecting dienyne 5 to nBu3SnH/AIBN conditions successfully triggered the C18-C2 radical cyclization/1,5-HAT/C7-C10 radical cyclization cascade reaction, which, followed by acidic workup to hydrolyze the vinyltin intermediate, produced hexacyclic compound 16 that contained the entire ring framework of the target molecule, (−)caldaphnidine O. Subsequently, a Swern oxidation converted the primary alcohol motif in intermediate 16 into the corresponding aldehyde moiety. On the basis of our previous findings in the synthesis of dapholdhamine B,13b a Horner−Wadsworth−Emmons reaction using nBuLi and phosphonate 17,27 followed by acidic and then basic workup, afforded the carboxylic acid methyl ester 18. Finally, a diastereoselective hydrogenation28 of the C18-C20
ACS Paragon Plus Environment
Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
alkene motif in compound 18, proceeding from the convex face of this caged substrate, successfully yielded, for the first time, the bukittinggine-type alkaloid (−)-caldaphnidine O. The synthetic (−)-caldaphnidine O gave spectral characteristics (1H- and 13CNMR spectroscopy and HRMS data) consistent with those of the naturally occurring (−)-caldaphnidine O, while the optical rotation is also in good agreement with that of the natural product (synthetic: []D20 = −71.6 (c = 0.5 in MeOH); natural: []D20 = −42.0 (c = 0.19 in MeOH).17 In conclusion, we have accomplished the first and enantioselective synthesis of the highly complex bukittingginetype alkaloid (−)-caldaphnidine O in 22 steps from 1,3cyclohexanedione (or 15 steps from the known chiral synthon 7). The highlights of our concise approach included an IMAM reaction, an efficient ring expansion reaction sequence, Sm(II)/Fe(III)-mediated Kagan-Molander coupling that forms the cyclopentane moiety, and a radical cyclization cascade reaction that constructed the entire hexacyclic ring system of the bukittinggine-type alkaloids from tetracyclic dienyne 5. This highly efficient radical cyclization cascade reaction29 should pave the way for the synthesis of other bukittinggine-type alkaloids and natural products with related chemical structures.
ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Experimental procedures and spectral data for all new compounds (PDF).
AUTHOR INFORMATION Corresponding Author *
[email protected] Author Contributions †These
authors contributed equally.
Notes The authors declare no competing financial interests.
ACKNOWLEDGMENT Dedicated to Professor Clayton H. Heathcock. Financial support from NSFC (21772082), SZDRC Discipline Construction Program, Shenzhen Nobel Prize Scientists Laboratory Project (C17783101) and SZSTI (JCYJ20170817110515599 and KQJSCX20170728154233200) are greatly appreciated. The authors also thank Dr. Xiaoyong Chang (SUSTech) for single crystal X-ray diffraction analysis.
REFERENCES (1) (a) Yang, S.-P.; Yue, J.-M. Discovery of structurally diverse and bioactive compounds from plant resources in China. Acta Pharmacol. Sin. 2012, 33, 11471158. (b) Kobayashi, J.; Kubota, T. The Daphniphyllum alkaloids. Nat. Prod. Rep. 2009, 26, 936962. (c) Kang, B.; Jakubec, P.; Dixon, D. J. Strategies towards the synthesis of calyciphylline A-type Daphniphyllum alkaloids. Nat. Prod. Rep. 2014, 31, 550562. (d) Chattopadhyay, A. K.; Hanessian, S. Recent progress in the chemistry of Daphniphyllum alkaloids. Chem. Rev. 2017, 117, 41044146. (2) For synthetic studies published after ref 1d, see: (a) Li, J. L.; Shi, H. W.; Wang, Q.; Chai, Y. H.; Yang, J. Synthesis of the ABC tricyclic system of daphnicyclidin A. Org. Lett. 2017, 19, 14971499. (b) Boissarie, P.; Bélanger, G. Short approach toward the nonracemic A,B,E tricyclic core of calyciphylline B-type alkaloids. Org. Lett. 2017, 19, 37393742. (c) Liu, Y. M.; Li, F.; Wang, Q.; Yang, J. Synthesis of the AE bicyclic of Daphniphyllum alkaloid yuzurine. Tetrahedron 2017, 73,
63816385. (d) Shao, H.; Bao, W.; Jing, Z.-R.; Wang, Y.-P.; Zhang, F.M.; Wang, S.-H.; Tu, Y.-Q. Construction of the [6,5,7,5] tetracyclic core of calyciphylline A type alkaloids via a tandem semipinacol rearrangement/Nicholas Reaction. Org. Lett. 2017, 19, 46484651. (e) Lopez, A. M.; Ibrahim, A. A.; Rosenhauer, G. J.; Sirinimal, H. S.; Stockdill, J. L. Tin-free access to the ABC core of the calyciphylline A alkaloids and unexpected formation of a D-ring-contracted tetracyclic core. Org. Lett. 2018, 20, 22162219. (f) Sasano, Y.; Koyama, J.; Yoshikawa, K.; Kanoh, N.; Kwon, E.; Iwabuchi, Y. Stereocontrolled construction of ABCD tetracyclic ring system with vicinal all-carbon quaternary stereogenic centers of calyciphylline A type alkaloids. Org. Lett. 2018, 20, 30533056. (g) Yamada, R.; Fukuyama, T.; Yokoshima, S. Synthetic Studies of the Daphniphyllum Alkaloids: A cooperative reaction of proximal functional groups forming a tetracyclic system. Org. Lett. 2018, 20, 45044606. (h) Li, Y.; Dong, Q.; Xie, Q.; Tang, P.; Zhang, M.; Qin, Y. Enantioselective synthesis of ABCF tetracyclic framework of Daphniphyllum alkaloid calyciphylline N. Org. Lett. 2018, 20, 50535057. (i) Qiu, Y.; Zhong, J.; Du, S.; Gao, S. Synthetic studies on daphniglaucins. Chem. Commun. 2018, 54, 55545557. (j) Kitabayashi, Y.; Fukuyama, T.; Yokoshima, S. Synthesis of the [7-5-5] tricyclic core of Daphniphyllum alkaloids. Org. Biomol. Chem. 2018, 16, 35563559. (k) Mo, X.-F.; Li, Y.-F.; Sun, M.-H.; Dong, Q.-Y.; Xie, Q.-X.; Tang, P.; Xue, F.; Qin, Y. Asymmetric synthesis of ABC tricyclic core in Daphniphyllum alkaloid 21-deoxy-macropodumine D. Tetrahedron Lett. 2018, 59, 19992004. (l) Cox, J. B.; Wood, J. L. Synthetic studies toward longeracemine: The intramolecular [4+2] cycloaddition of 3H-pyrroles. Tetrahedron 2018, 74, 45394549. (m) Gao, L.; Cheng, B.; Yue, H.; Cao, S.; Wang, J.-L.; Xu, L. A bioinspired approach for construction of the [75-6-5] all-carbon tetracyclic core of logeracemin A. Org. Chem. Front. 2019, 6, 813816. (n) Deng, M.; Yao, Y.; Li, X.; Li, N.; Zhang, X.; Liang, G. Rapid construction of the ABCE tetracyclic tertiary amine skeleton in Daphenylline enabled by an amine−borane complexation strategy. Org. Lett. 2019, 21, 3290−3294. (o) Chen, Y.; Hu, J.; Guo, L.-D.; Tian, P.; Xu, T.; Xu, J. Synthesis of the core structure of daphnimacropodines. Org. Lett. 2019, 21, 4309−4312. (p) Zhang, Y.; Guo, L.-D.; Xu, J. Efficient synthesis of the AC ring system of daphnilactone B. Youji Huaxue 2019, 39, 1079−1084. (q) Sun, H.; Wu, G.; Xie, X. Synthetic studies towards daphniyunnine B: Construction of AC bicyclic skeleton with two vicinal all carbon quaternary stereocenters. Chin. Chem. Lett. 2019, 30, 1538−1540. (r) Jansana, S.; Diaba, F.; Bonjoch, J. Stereocontrolled synthesis of the daphenylline pentacyclic ACDEF ring system. Org. Lett. 2019, 21, 5757−5761. (s) Hayakawa, I.; Nagatani, R.; Ikeda, M.; Yoo, D.; Saito, K.; Kigoshi, H.; Sakakura, A. Toward the synthesis of YuzurimineType alkaloids: Stereoselective construction of the heterocyclic portions of deoxyyuzurimine and macrodaphnine. Org. Lett. 2019, DOI: 10.1021/acs.orglett.9b02232. (3) (a) Wu, H.; Zhang, X.; Ding, L.; Chen, S.; Yang, J.; Xu, X. Daphniphyllum alkaloids: Recent findings on chemistry and pharmacology. Planta Med. 2013, 79, 15891598. (b) Xu, J.-B.; Zhang, H.; Gan, L.-S.; Han, Y.-S.; Wainberg, M. A.; Yue, J.-M. Logeracemin A, an anti-HIV Daphniphyllum alkaloid dimer with a new carbon skeleton from Daphniphyllum longeracemosum. J. Am. Chem. Soc. 2014, 136, 76317633. (4) (a) Piettre, S.; Heathcock, C. H. Biomimetic total synthesis of proto-daphniphylline, Science, 1990, 248, 15321534. (b) Heathcock, C. H.; Davidsen, S. K.; Mills, S.; Sanner, M. A. Total synthesis of (.+-.)methyl homodaphniphyllate. J. Am. Chem. Soc. 1986, 108, 56505651. (c) Ruggeri, R. B.; Heathcock, C. H. Daphniphyllum alkaloids. Part 7. Biomimetic total synthesis of (.+-.)-methyl homodaphniphyllate. J. Org. Chem. 1990, 55, 37143715. (d) Heathcock, C. H.; Kath, J. C.; Ruggeri, R. B. Daphniphyllum alkaloids. 16. Total synthesis of (+)codaphniphylline. J. Org. Chem. 1995, 60, 11201130. (e) Ruggeri, R. B.; Hansen, M. M.; Heathcock, C. H. Total synthesis of (.+-.)-methyl homosecodaphniphyllate. A remarkable new tetracyclization reaction. J. Am. Chem. Soc. 1988, 110, 87348736. (f) Stafford, J. A.; Heathcock, C. H. Daphniphyllum alkaloids. Part 8. Asymmetric total synthesis of (−)secodaphniphylline. J. Org. Chem. 1990, 55, 54335434. (g) Heathcock, C. H.; Stafford, J. A.; Clark, D. L. Daphniphyllum alkaloids. 14. Total synthesis of (.+-.)-bukittinggine. J. Org. Chem. 1992, 57, 25752585. (h) Ruggeri, R. B.; McClure, K. F.; Heathcock, C. H. Daphniphyllum alkaloids. Part 5. Total synthesis of (.+-.)-daphnilactone A: a novel fragmentation reaction. J. Am. Chem. Soc. 1989, 111, 15301531. (5) Weiss, M. E.; Carreira, E. M. Total synthesis of (+)‐daphmanidin E. Angew. Chem., Int. Ed. 2011, 50, 1150111505.
ACS Paragon Plus Environment
Page 4 of 6
Page 5 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Journal of the American Chemical Society (6) (a) Shvartsbart, A.; Smith, A. B., III Total synthesis of (−)calyciphylline N. J. Am. Chem. Soc. 2014, 136, 870873. (b) Shvartsbart, A.; Smith, A. B., III The Daphniphyllum alkaloids: Total synthesis of (−)calyciphylline N. J. Am. Chem. Soc. 2015, 137, 35103519. (7) (a) Lu, Z. Y.; Li, Y.; Deng, J.; Li, A. Total synthesis of the Daphniphyllum alkaloid daphenylline. Nat. Chem. 2013, 5, 679684. (b) Chen, Y.; Zhang, W. H.; Ren, L.; Li, J.; Li, A. Total syntheses of daphenylline, daphnipaxianine A, and himalenine D. Angew. Chem., Int. Ed. 2018, 57, 952956. (c) Zhang, W. H.; Ding, M.; Li, J.; Guo, Z. C.; Lu, M.; Chen, Y.; Liu, L. C.; Shen, Y. H.; Li, A. Total synthesis of hybridaphniphylline B. J. Am. Chem. Soc. 2018, 140, 42274231. (d) Li, J.; Zhang, W. H.; Zhang, F.; Chen, Y.; Li, A. Total synthesis of longeracinphyllin A. J. Am. Chem. Soc. 2017, 139, 1489314896. (8) For the synthesis of a putative member of calyciphylline B-type alkaloids, see: Chattopadhyay, A. K.; Ly, V. L.; Jakkepally, S.; Berger, G.; Hanessian, S. Total synthesis of isodaphlongamine H: A possible biogenetic conundrum. Angew. Chem., Int. Ed. 2016, 55, 25772581. (9) Yamada, R.; Adachi, Y.; Yokoshima, S.; Fukuyama, T. Total synthesis of (−)‐daphenylline. Angew. Chem., Int. Ed. 2016, 55, 60676070. (10) Chen, X.; Zhang, H.-J.; Yang, X.; Lv, H.; Shao, X.; Tao, C.; Wang, H.; Cheng, B.; Li, Y.; Guo, J.; Zhang, J.; Zhai, H. Divergent total syntheses of (−)‐daphnilongeranin B and (−)‐daphenylline. Angew. Chem., Int. Ed. 2018, 57, 947951. (11) Shi, H.; Michaelides, I. N.; Darses, B.; Jakubec, P.; Nguyen, Q. N. N.; Paton, R. S.; Dixon, D. J. Total synthesis of (−)-himalensine A. J. Am. Chem. Soc. 2017, 139, 1775517758. (12) Xu, B.; Wang, B.; Xun, W.; Qiu, F. G. Total Synthesis of (−)Daphenylline. Angew. Chem., Int. Ed. 2019, 58, 5754−5757. (13) (a) Chen, Y.; Hu, J.; Guo, L.-D.; Zhong, W.; Ning, C.; Xu, J. A concise total synthesis of (−)-himalensine A. Angew. Chem. Int. Ed. 2019, 58, 7390−7394. (b) Guo, L.-D.; Hou, J.; Tu, W.; Zhang, Y.; Zhang, Y.; Chen, L.; Xu, J. Total synthesis of dapholdhamine B and dapholdhamine B lactone. J. Am. Chem. Soc. 2019, 141, 11713−11720. (14) Zhong, J.; Chen, K.; Qiu, Y.; He, H.; Gao, S. A unified strategy to construct the tetracyclic ring of Calyciphylline A alkaloids: Total synthesis of himalensine A. Org. Lett. 2019, 21, 3741−3745. (15) Hugelshofer, C. L.; Palani, V.; Sarpong, R. Calyciphylline B-type alkaloids: Total syntheses of (−)-daphlongamine H and (−)isodaphlongamine H. J. Am. Chem. Soc. 2019, 141, 8431−8435. (16) (a) Zhang, H.; Hay, E. B.; Geib, S. J.; Curran, D. P. Radical cyclizations of cyclic ene sulfonamides occur with β-elimination of sulfonyl radicals to form polycyclic imines. J. Am. Chem. Soc. 2013, 135, 16610−16617. For related studies, see: (b) Cossy, J.; Cases, M.; Pardo, D. G. Approaches to a synthesis of α-kainic acid. Tetrahedron 1999, 55, 6153−6166. (c) Campbell, N. E.; Sammis, G. M. Singleelectron/pericyclic cascade for the synthesis of dienes. Angew. Chem. Int. Ed. 2014, 53, 62286231. (d) Tong, X.; Shi, B.; Liang, K.; Liu, Q.; Xia, C. Enantioselective total synthesis of (+)‐Flavisiamine F via late‐stage visible‐light‐induced photochemical cyclization. Angew. Chem. Int. Ed. 2019, 58, 54435446. (17) Zhang, C.-R.; Yang, S.-P.; Yue, J.-M. Alkaloids from the twigs of Daphniphyllum calycinum. J. Nat. Prod. 2008, 71, 1663−1668. (18) (a) Girard, P.; Namy, J. L.; Kagan, H. B. Divalent lanthanide derivatives in organic synthesis. 1. Mild preparation of samarium iodide and ytterbium iodide and their use as reducing or coupling agents. J. Am. Chem. Soc. 1980, 102, 26932698. (b) Molander, G. A.; Etter, J. B. Lanthanides in organic synthesis. Synthesis of bicyclicalcohols. Tetrahedron Lett. 1984, 25, 32813284. (c) Molander, G. A.; Etter, J. B. Lanthanides in organic synthesis. 3. A general procedure for five- and sixmembered ring annulation. J. Org. Chem. 1986, 51, 17781786. (d) Molander, G. A.; McKie, J. A. A facile synthesis of bicyclo[m.n.1]alkan1-ols. Evidence for organosamarium intermediates in the samarium(II) iodide promoted intramolecular Barbier-type reaction. J. Org. Chem. 1991, 56, 41124120. (19) Zhang, X.-M.; Wang, M.; Tu, Y.-Q.; Fan, C.-A.; Jiang, Y.-J.; Zhang, S.-Y.; Zhang, F.-M. Prolinamide/PPTS-catalyzed Hajos–Parrish
annulation: Efficient approach to the tricyclic core of cylindricine-type alkaloids. Synlett 2008, 28312835. (20) (a) Luche, J. L.; Petrier, C.; Lansard, J. P.; Greene, A. E. Ultrasound in organic synthesis. 4. A simplified preparation of diarylzinc reagents and their conjugate addition to .alpha.-enones. J. Org. Chem. 1983, 48, 38373839. (b) Smith III, A. B.; Leenay, T. L. Indole-diterpene synthetic studies.: 3. A unified synthetic strategy for the simple indole tremorgens. Tetrahedron Lett. 1988, 29, 27872790. (c) Fox, M. E.; Li, C.; Marino, J. P.; Overman, L. E. Enantiodivergent total syntheses of (+)and (−)-scopadulcic acid A. J. Am. Chem. Soc. 1999, 121, 54675480. (d) Díaz, S.; Cuesta, J.; González, A.; Bonjoch, J. Synthesis of (−)-nakamurol A and assignment of absolute configuration of diterpenoid (+)-Nakamurol A. J. Org. Chem. 2003, 68, 74007406. (21) McMurry, J. E.; Scott, W. J. A method for the regiospecific synthesis of enol triflates by enolate trapping. Tetrahedron Lett. 1983, 24, 979−982. (22) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya, Y. Reactions of carbonyl compounds with Grignard reagents in the presence of cerium chloride. J. Am. Chem. Soc. 1989, 111, 4392−4398. (23) Brown, H. C.; Rathke, M. W.; RogiĆ, M. M.; DeLue, N. R. Organoboranes for synthesis. 9. Rapid reaction of organoboranes with iodine under the influence of base. a convenient procedure for the conversion of alkenes into iodides via hydroboration. Tetrahedron 1988, 44, 2751−2762. (24) Stüdemann, T.; Ibrahim-Ouali, M.; Cahiez, G.; Knochel, P. Stereoselective nickel and manganese catalyzed cyclizations of 5haloketones. Synlett 1998, 1998, 143144. (25) Crystallographic data for compound 14a (CCDC 1940308) and compounnd 14b (CCDC 1940309) has been deposited at the Cambridge Crystallographic Data Centre. (26) For selected anti-elimination examples using Burgess reagent, see: (a) Zhao, Y.-J.; Li, B.; Serena Tan, L.-J.; Shen, Z.-L.; Loh, T.-P. Enantioselective cationic polyene cyclization vs enantioselective intramolecular carbonyl-ene reaction. J. Am. Chem. Soc. 2010, 132, 1024210244. (b) Wang, B.-L.; Gao, H.-T. Li, W.-D. Z. Total Synthesis of (+)-Iresin. J. Org. Chem. 2015, 80, 52965301. (c) Peter, D.; Brückner, R. A new approach to models of the 4,5‐dihydroxycyclopentenone core of the Kodaistatins A–D: Elucidation of the diol configuration in Kodaistatin A. Chem. Eur. J. 2017, 23, 1210412109. (d) Hermann, M.; Wassy, D.; Kratzert, D.; Esser, B. Dibenzo[a,e]pentalenophanes: Bending a nonalternant hydrocarbon. Chem. Eur. J. 2018, 24, 73747387. (27) Mikołajczyk, M.; Grzejszczak, S.; Zatorski, A.; Mlotkowska, B.; Gross, H.; Costisella, B. Organosulphur compounds—XVIII: A new and general synthesis of ketene S,S- and O,S-thioacetals based on the HornerWittig reaction. Tetrahedron 1978, 34, 30813088. (28) Denmark, S. E.; Baiazitov, R. Y. Tandem double-intramolecular [4+2]/[3+2] cycloadditions of nitroalkenes. Studies toward a total synthesis of daphnilactone B: piperidine ring construction. J. Org. Chem. 2006, 71, 593605. (29) For selected recent reviews, see: (a) Yan, M.; Lo, J. C.; Edwards, J. T.; Baran, P. S. Radicals: Reactive Intermediates with Translational Potential. J. Am. Chem. Soc. 2016, 138, 12692−12714. (b) Plesniak, M. P.; Huang, H-M; Procter, D. J. Radical cascade reactions triggered by single electron transfer. Nature Rev. Chem. 2017, 1, 0077. (c) Inoue, M. Evolution of radical-based convergent strategies for total syntheses of densely oxygenated natural products. Acc. Chem. Res. 2017, 50, 460464. (d) Romero, K. J.; Galliher, M. S.; Pratt, D. A.; Stephenson, C. R. J. Radicals in Natural Product Synthesis. Chem. Soc. Rev. 2018, 47, 7851−7866. (e) Hung, K.; Hu, X.; Maimone, T. J. Total Synthesis of Complex Terpenoids Employing Radical Cascade Processes. Nat. Prod. Rep. 2018, 35, 174−202. (f) Smith, J. M.; Harwood, S. J.; Baran, P. S. Radical Retrosynthesis. Acc. Chem. Res. 2018, 51, 1807−1817. (g) Romero, K. J.; Galliher, M. S.; Pratt, D. A.; Stephenson, C. R. J. Radicals in natural product synthesis. Chem. Soc. Rev. 2018, 47, 78517866. (h) Pitre, S. P.; Weires, N. A.; Overman, L. E. Forging C(sp3)-C(sp3) Bonds with Carbon-Centered Radicals in the Synthesis of Complex Molecules. J. Am. Chem. Soc. 2019, 141, 2800−2813.
ACS Paragon Plus Environment
Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
OH
Page 6 of 6
CO2Me
Radical cyclization cascade
N
N
H
H ()-Caldaphnidine O
ACS Paragon Plus Environment
6
