Subscriber access provided by University of Newcastle, Australia
Article
Furans as Versatile Synthons: Total Syntheses of Caribenol A and Caribenol B Hong-Dong Hao, and Dirk Trauner J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b00234 • Publication Date (Web): 20 Feb 2017 Downloaded from http://pubs.acs.org on February 22, 2017
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 free 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 accessible to all readers and 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.
Journal of the American Chemical Society 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 7
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
Furans as Versatile Synthons: Total Syntheses of Caribenol A and Caribenol B Hong-Dong Hao and Dirk Trauner* Department of Chemistry and Center for Integrated Protein Science, Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, 81377 München, Germany ABSTRACT: Two complex norditerpenoids, caribenols A and B, were accessed from a common building block. Our synthesis of caribenol A features the Me Me Me Me H H H H diastereoselective formation of the sevenH OH membered ring through a Friedel-Crafts OH HO Me Me Me Me triflation and a late stage oxidation of a furan H Me O O O HO Me O O ring. The first synthesis of caribenol B was O caribenol A caribenol B amphilectolide achieved using an intramolecular common building block organocatalytic α-arylation. An unusual intramolecular aldol addition was developed for the assembly of its cyclopentenone moiety and the challenging trans-diol moiety was installed through a selective nucleophilic addition to a hydroxy 1,2-diketone. Our overall synthetic strategy, which also resulted in a second-generation synthesis of amphilectolide, confirms the usefulness of furans as powerful nucleophiles and versatile synthons.
INTRODUCTION
Furans teeter on the edge of aromaticity and can behave both as arenes and as very electron-rich dienes. As such, they can undergo a wide variety of chemical transformations, including electrophilic substitutions, metalations, cycloadditions and oxidations (Scheme 1). If extended to furyl carbinols, their synthetic power is increased even more, allowing for Piancatelli rearrangements and Achmatowicz reactions with subsequent cycloadditions to access carbocyclic systems. Often associated with a significant increase in molecular complexity, these transformations have been extensively exploited in the total synthesis of complex target molecules. 1 O
E
Many of the functional groups and ring systems accessible from furans can be found in natural products isolated from the Caribbean sea plume Pseudopterogorgia. These include diterpenes and norditerpenes with novel carbon skeletons,2 such as aberrarone, caribenol A and caribenol B (Figure 1) that have shown biological activity against Mycobacterium tuberculosis H37Rv and antiplasmodial activity. Figure 1. Natural Products isolated from Pseudopterogorgia elisabethae. Me
H H
O
O
H
O O Me
Me
Me
[M]
O
OH elisabethin A (2)
Me H H OH Me
O
HO OH
HO O
O
Me O
caribenol B (4)
O
Me H
O O
O
O O
Me H O
O
aberrarone (1)
O
Me H
H
amphilectolide (3) Me H
Me H
HO
OH Me
Me
Me OH O
Me O O caribenol A (5)
O
sandresolide B (6)
O O
O
O
OH
O
Scheme 1. Furans and furyl carbinols as powerful synthons.
The caribenols A and B became attractive targets for the synthetic community due to their intriguing biological activities as well as their unique skeletons. 2i Caribenol A was shown to possess a caged structure and tricarbocyclic ring system with six stereocenters. Its first synthesis by Yang and co-workers 3a-3c was based on an intramolecular
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
Diels-Alder reaction and a late-stage oxidation to install the hydroxy butenolide moiety. More recently, Luo and coworkers reported an approach to caribenol A3d that hinges on a Cope rearrangement and a C-H insertion reaction. Some years ago, our group launched a program aimed at a unified synthesis of the Pseudopterogorgia terpenoids. To this end, we developed a scalable synthesis of furan building block 7 from (−)-β-citronellol, which could be converted into two natural products: sandresolide B and amphilectolide4 (Scheme 2). We now provide an account of our syntheses of caribenols A and B as well as a second generation synthesis of amphilectolide. They are also based on furan 7 and required the development and application of new methodology that exploits the special reactivity of furans.5 Scheme 2. Previous Work Toward Natural Products Total Syntheses Using Furan Building Block 7
Page 2 of 7
Scheme 3. Failed Attempts Towards Caribenol A. Me H
Me H
[Rh(CO)2Cl]2
H2SO4, HCOOH Me
Me
(39%)
O
O
O
8
9 Me H
Me H
H
JohnPhosAu(MeCN)SbF6 Me
(45%)
Me O
Me O
10
11
Scheme 4. Revised Retrosynthetic Analysis of Caribenol A. Me H
Me H
cross coupling H
H
B OH
A
Me Me O
furan O oxidation caribenol A (5)
O
Me Me
O
12
Friedel-Crafts
Me H
Me H H
HO
Me O
RESULTS AND DISCUSSION
Our initial synthetic strategies toward caribenol A focused on Pauson-Khand reactions6 and gold-catalyzed cycloisomerizations7 to forge the 5-7-6 ring system of the target molecule (Scheme 3). Although allene 8 underwent a clean allenic Pauson-Khand reaction, the procedure suffered from low yields and was difficult to scale up due to the instability of 8. Enyne 10, on the other hand, provided the unwanted 6-7-6 isomer 11, which bears a quaternary carbon with the correct absolute configuration. Extensive efforts to reverse the regioselectivity of this Aumediated process proved unsuccessful. (For the details on the synthesis of 8 and 10, see Supporting Information). Based on these results and considering the high nucleophilicity8 of the furan ring, we next explored our Friedel-Crafts triflation9 for the construction of the carbotricyclic framework. Our corresponding retrosynthetic analysis is shown in Scheme 4. It calls for the elaboration of cyclopentenone 13 from furan building block 7. Following closure of the seven-membered ring, 12 would be converted into caribenol A via cross coupling and oxidation of the furan ring (Scheme 4). Toward cyclopentenone 13, furan 7 was first converted to allylic alcohol 15 by Swern oxidation, Wittig olefination
O 7
Me 13 O
and DIBAL-H reduction in excellent yield (Scheme 5). The terminal alkene 1610 was then made from 15 using Myers’ allylic reductive transposition method.11 A subsequent cross-metathesis and transformation of the resulting methyl ester to an Evans oxazolidine afforded 18. Diastereoselective conjugate addition promoted by TMSCl and HMPA12 then gave alkene 19 which was converted into 20 through alcoholysis13 and Weinreb amide14 formation. The requisite cyclopentenone 13 was then constructed through Grignard addition and a clean ring closing metathesis,15 which preserved the stereochemical integrity at C(3). The relative configuration of 13 was verified by X-ray diffraction (see Supporting Information). With enone 13 at hand, we proceeded to investigate the closure of the seven-membered ring. A variety of Lewis and Brønsted acids failed to afford the desired tetracycle 12 in appreciable ammounts (see Supporting information for details). However, exposure of enone 13 to our FriedelCrafts triflation conditions led to clean formation of the vinyl triflate 21 as a single diastereomer.9 The hydrolysis of 21 to the corresponding cyclopentanone 12 was not trivial, but after screening several conditions we found that TMSOK in THF16 smoothly achieved this transformation. The structure of 12 was verified by X-ray diffraction (see Supporting Information). With the core structure of caribenol A in hand, the stage was now set to add the missing methyl group and introduce the double bond in the correct position. Using standard conditions (KHMDS, Comins’ reagent), we again arrived at the undesired isomer 21. Presumably, this was due to a directing effect of the furan oxygen.
ACS Paragon Plus Environment
Page 3 of 7
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 5. Total Synthesis of Caribenol A. Me H HO
Me
b)
c) DIBAL-H
7
Me
MeO2C
CO2Me
Ph3P (86% over two steps)
O
Me H
Me H
a) (COCl)2, DMSO then NEt3
Me H
d) Ph3P, DEAD
HO
Me
(92%) O
O 14
Me
IPNBSH then HFIP, H2O
O 16
15 e) H-G II CO2Me
O O
O
Me H
O
MgBr h) CuCN, TMSCl, HMPA
N Ph
Me H
Me H
f) TMSOK
N
(86%)
Me
19
O
O
Me
Ph
O
O
18
O g) Piv-Cl, NEt3 (76% over O NLi two steps)
(76% over i) Sm(OTf)3, MeOH two steps) j) HNMe(OMe)• HCl Me2AlCl O MeO
k)
N
O 17
Me H
H
MgBr (94%)
3
Me
O
Me
H
m) 2,6-Di-tert-butyl pyridine
l) H-G II (77%) 20
Me
MeO2C
Ph
Me H
Me H
(63% over two steps)
Tf2O
O
Me
TfO
Me O 21
13
O
n) TMSOK (53% over two steps)
p) N2H4• H2O, Et3N then I2, TMG (56%) q) Me4Sn, AsPh3 Pd(PPh3)4 (33%)
Me H H OH
Me H OH
Me O
Me O O
Me
O
22 o
H
(72%)
Me O O
caribenol A (5) a
Me H
o) CH3CO3H NaOAc
H
Me Me O
12
Reagents and conditions: (a) (COCl)2, DMSO, CH2Cl2, − 78 C, then NEt3, − 78 C; (b) Methyl (triphenylphosphoranylidene)acetate, toluene, 85 oC (86% over two steps); (c) DIBAL-H, CH2Cl2, − 78 oC to 0 oC, (92%); (d) Ph3P, DEAD, IPNBSH, THF, then HFIP, H2O; (e) Hoveyda-Grubbs catalyst 2nd catalyst (7 mol%), methylacylate (20 equiv), CH2Cl2, r.t. (63% over two steps); (f) TMSOK, THF, 50 oC, (94%); (g) Piv-Cl, NEt3, − 78 oC to 0 oC, (85%); (h) Isopropenylmagnesium bromide (4.5 equiv), CuCN (2.25 equiv), Et2O, then HMPA, − 78 oC, then 18, TMSCl, THF, − 78 oC, (86%); (i) Sm(OTf)3, MeOH, 50 o C, (88%); (j) HNMe(OMe) • HCl (10 equiv), Me2AlCl (10 equiv), 0 oC to r.t. (86%); (k) Vinylmagnesium bromide (5 equiv), THF, 0 oC, (94%); (l) HoveydaGrubbs catalyst 2nd catalyst (10 mol%), toluene, reflux, (77%); (m) 2,6-Di-tert-butylpyridine (2 equiv), Tf2O (3 equiv), CH3CN; (n) TMSOK, THF, 50 oC, ( 53% over two steps); (o) CH3CO3H (2.2 equiv), NaOAc (2.3 equiv), CH2Cl2, (72%). (p) N2H4 (2 equiv), Et3N (3 equiv), EtOH, 50 oC, then I2 (2 equiv), TMG (3 equiv), (56%); (q) Me4Sn (2 equiv), AsPh3 (20 mol%), Pd(PPh3)4 (5 mol%), NMP, 60 oC, (33%). IPNBSH = N-Isopropylidene-N’-2-nitrobenzenesulfonyl hydrazine, HFIP = Hexafluoroisopropanol, TMG = Tetramethylguanidine, NMP = N-Methyl-2-pyrrolidone.
Consequently, oxidation of the furan ring was first effected using peracetic acid17 to provide butenolide 22, an intermediate in Yang’s synthesis of caribenol A. 18 Using Barton’s protocol for vinyl iodide formation followed by Stille coupling, synthetic caribenol A was obtained and found to be identical in all respects with the natural product (see Supporting Information). We next turned our attention to caribenol B, which features a fully substituted cyclopentenone ring containing a trans-1,2-diol moiety. This is a rare structural motif in natural products19 due to its instability under either acidic or basic conditions. We initially attempted to access this challenging dihydroxycyclopentenone from a furan through the Piancatelli rearrangement or an Achmatowicz reaction20 with subsequent ring contraction (Scheme 6). Retrosynthetic analysis of acetal 23 identified furfural 24 as a key intermediate. It could be traced back to aldehyde 25 and, via α-arylation, to aldehyde 26, which could be easily accessed from our previously used ester 14.
o
Our synthesis commenced with hydrogenation and DIBAL-H reduction of 14. The resulting aldehyde 26 was subjected to the radical cation cyclization21 catalyzed by 28, which, after in situ reduction, afforded the stable primary alcohol 29. The cyclization proved to be highly diastereoselective (d.r. 20:1) when the matched enantiomer22 of the catalyst was used. The configuration of the newly formed stereocenter23 at C(3) was confirmed by transformation of 29 into amphilectolide. The spectra of the natural product were identical in all respects to those previously reported.2d, 3d, 4 With these results in mind, we proceeded to pursue caribenol B. Furan 29 was subjected to Vilsmeier-Haack conditions, in the course of which the primary alcohol was also formylated, to provide furfural 31. Exposure to DIBAL-H, subsequent DMDO oxidation, and protection then yielded dihydropyran 34 in excellent yield. Unfortunately, 34 could not be converted into cyclopentenone 35 via retro-6π-electrocylization and aldol closure despite literature precedence24 and extensive efforts from our side (see Supporting information for details). Consequently, we modified our synthetic strategy to provide a better nucleophile for the aldol-type ring clo-
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
sure25 (For a detailed evolution of our synthetic strategy for caribenol B, see Supporting information). Scheme 6. Retrosynthetic Analysis of Caribenol B. Me H
Me H
OH Me
Me
RO
ring HO contraction
Me O Grignard rddition caribenol B (4)
O Achmatowicz
α-arylation Me H of aldehyde OHC
O 23
Me H
Me O
Me olefination
25
O 24
CHO
and the resulting aldehyde homologated by Van Leusen reaction27 to nitrile 38. Oxidation with DMDO28 presumably gave a cyanoketone 39, which underwent the desired aldol cyclization to yield the tertiary alcohol 40. The diastereoselectivity of this addition is presumably governed by the adjacent isobutenyl group. The structure of 40 was confirmed by single crystal X-ray diffraction (see Supporting Information).29 Hydroxylation of 40 using DMDO afforded the cyanohydrin 41 which was then treated with AgNO3 and 2,6-lutidine30, 31 to provide diketone 42 as the penultimate intermediate. To our delight, 42 underwent a diastereoselective Grignard addition,32 which afforded caribenol B as a single diastereomer.
Vilsmeier-Haack
Scheme 8. Attempted Achmatowicz Reaction and Ring Contraction.
Me H
Me H
Page 4 of 7
Me H
Me H
a) POCl3, DMF
OHC
Me O 26
MeO2C
Me
HO
Me
O 14
H
O
Me
(70%) O
O
O
CHO
31
29
b) DIBAL-H (90%)
Scheme 7. Organocatalytic α-Arylation and SecondGeneration Synthesis of Amphilectolide.
Me H
Me H
c) DMDO
HO HO
Me O
33
(88%)
HO
Me
O
O
Me H
Me H
for details see SI
TBSO MeO
Me O
34 a
OH
32
(93% over d) PPTS, MeOH two steps) e) TBSCl
O
X
TBSO
Me
MeO HO
O
35
Reagents and conditions: (a) POCl3, DMF, (70%); (b) DIBAL-H, CH2Cl2, (90%); (c) DMDO, CH2Cl2, (88%); (d) PPTS, MeOH, (100%); (e) TBSCl, imidazole, CH2Cl2, (93%).
a
Reagents and conditions: (a) Rh(PPh3)3Cl (10 mol%), H2 balloon, THF, 50 C, (98%); (b) DIBAL-H, CH2Cl2, − 78 oC; (c) (2R, 5R)-(+)-2-tert-Butyl-3methyl-5-benzyl-4-imidazolidinone trifluoroacetic acid salt (40 mol%), CAN (2.2 equiv), H2O (2 equiv), DME, − 20 oC, 18 h, then MeOH, NaBH4 (15 equiv), (66% over three steps); (d) CH3CO3H, NaOAc, CH2Cl2, (95%); (e) NaBH4, EtOH (82%); (f) TPAP (5 mol%), NMO, CH2Cl2, (60%); (g) nBuLi, isopropyltriphenylphosphonium iodide, THF, (45%). o
Our ultimately successful synthetic route toward caribenol B is shown in Scheme 9. It commenced with oxidative cyclization of aldehyde 26. The resulting unstable aldehyde 25 was immediately subjected to JuliaKocienski olefination to install the isobutenyl side chain in one pot. 26 Installation of this side chain at this stage by this method proved critical. Furan 37 was then formylated
In summary, we have achieved an asymmetric synthesis of caribenol A and the first total synthesis of caribenol B. Both of our syntheses are highly stereoselective and protecting group free.33 The nucleophilicity of furans was critical to the success of our program, as they were used in a Friedel-Crafts triflation and an intramolecular organocatalytic α-arylation. A novel strategy for the conversion of furfurals into cyclopentenones and a mild method for the hydrolysis vinyl triflates were also developed. The scope of the gold-catalyzed cycloisomerization shown in Scheme 3 is under active investigation in our laboratories and results will be reported in due course.
ACS Paragon Plus Environment
Page 5 of 7
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 9. Total Synthesis of Caribenol B.
a
Reagents and conditions: (a) DIBAL (1.2 equiv), CH2Cl2, − 78 oC; (b) (2R, 5R)-(+)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone trifluoroacetic acid salt (40 mol%), CAN (2.2 equiv), H2O (2 equiv), DME, − 20 oC, 18 h; (c) LiHMDS (12 equiv), 36 (12 equiv), − 78 oC , 1 h, then 0 oC (1 h), r.t (30 min), (26% over three steps); (d) POCl3 (1.5 equiv), DMF, (79%); (e) Tos-MIC (3 equiv), t-BuOK (4.5 equiv), THF, − 50 oC, then MeOH, 65 oC, (57%); (f) DMDO (1 equiv), K2CO3 (2 equiv), Na2SO4, CH2Cl2, (77%); (g) DMDO (2 equiv), K2CO3 (2 equiv), Na2SO4, O2 balloon, CH2Cl2, (54%); (h) AgNO3 (10 equiv), 2,6lutidine (10 equiv), CH3CN; (i) MeMgBr (3 equiv), Et2O, (45% over two steps).
ASSOCIATED CONTENT Supporting Information Experimental procedures and data. This material is available free of charge via internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author E-mail:
[email protected] Notes The authors declare no competing financial interest
ACKNOWLEDGMENT We thank the Deutsche Forschungsgemeinschaft (SFB 749) for financial support. Dr. Peter Mayer is acknowledged for Xray analyses. We thank Felix Hartrampf, Giulio Volpin, Dr. Julius R. Reyes and Dr. Bryan Matsuura (all LMU Munich) for helpful discussions during the preparation of this manuscript and Irina Albrecht for early contribution to the project.
REFERENCES (1) For reviews, see: (a) Palframan, M. J.; Pattenden, G. Chem. Commun. 2014, 50, 7223. (b) Schindler, C. S.; Carreira, E. M. Chem. Soc. Rev. 2009, 38, 3222. (c) Merino, P.; Tejero, T.; Delso, J. I.; Matute, R. Curr. Org. Chem. 2007, 11, 1076. (d) Kappe, C. O.; Murphree, S. S.; Padwa, A. Tetrahedron 1997, 53, 14179. (e) Raczko, J.; Jurczak, J. In Studies in Natural Products Chemistry; Attaur-Rahman, Ed.; Elsevier: Amsterdam, 1995; Vol. 16, 639. For selected examples, see: (f)
Martinez, L. P.; Umemiya, S.; Wengryniuk, S. E.; Baran, P. S. J. Am. Chem. Soc. 2016, 138, 7536. (g) Nilson, M. G.; Funk, R. L. J. Am. Chem. Soc. 2011, 133, 12451. (h) Nicolaou, K. C.; Kang, Q.; Ng, S. Y.; Chen, D. Y. K. J. Am. Chem. Soc. 2010, 132, 8219. (i) Mihelcic, J.; Moeller, K. D. J. Am. Chem. Soc. 2004, 126, 9106. (j) Schreiber, S. L.; Satake, K. J. Am. Chem. Soc. 1984, 106, 4186. (k) Miller, A. K.; Hughes, C. C.; KennedySmith, J. J.; Gradl, S. N. Trauner, D. J. Am. Chem. Soc. 2006, 128, 17057. (l) Roethle, P. A.; Hernandez, P. T.; Trauner, D. Org. Lett. 2006, 8, 5901. (m) Stichnoth, D.; Kölle, P.; Kimbrough, T. J.; Riedle, E.; de Vivie-Riedle, R.; Trauner, D. Nat. Commun. 2014, 6, 5597. (2) (a) Rodríguez, A. D.; González, E.; Huang, S. D. J. Org. Chem. 1998, 63, 7083. (b) Rodríguez, A. D.; Ramírez, C.; Rodríguez, I. I. J. Nat. Prod. 1999, 62, 997. (c) Rodríguez, A. D.; Ramírez, C.; Rodriguez, I. I.; Tetrahedron. Lett. 1999, 40, 7627. (d) Rodríguez, A. D.; Ramírez, C.; Medina, V.; Shi, Y. P. Tetrahedron. Lett. 2000, 41, 5177. (e) Rodríguez, A. D.; Shi, Y. P. Tetrahedron 2000, 56, 9015. (f) Rodríguez, A. D.; Ramírez, C. Org. Lett. 2000, 2, 507. (g) Rodríguez, A. D.; Ramírez, C.; Rodríguez, I, I.; Barnes, C. L. J. Org. Chem. 2000, 65, 1390. (h) Rodríguez, A. D.; Ramírez, C.; Shi, Y. P. J. Org. Chem. 2000, 65, 6682. (i) Wei, X.; Rodríguez, I. I.; Rodríguez, A. D. Bames, C. L. J. Org. Chem. 2007, 72, 7386. (j) Rodríguez, I.; Rodríguez, A. D.; Zhao, H. J. Org. Chem. 2009, 74, 7581. (3) For total syntheses of caribenol A, see: (a) Liu, L. Z.; Han, J. C.; Yue, G. Z.; Li, C. C.; Yang, Z. J. Am. Chem. Soc. 2010, 132, 13608. (b) Han, J. C.; Liu, L. Z.; Chang, Y. Y.; Yue, G. Z.; Guo, J.; Zhou, L. Y.; Li, C. C.; Yang, Z. J. Org. Chem. 2013, 78, 5492. (c) Han, J. C.; Liu, L. Z.; Li, C. C.; Yang, Z. Chem. Asian. J. 2013, 8, 1972. (d) Yu, X. R.; Su, F.; Liu, C.; Yuan, H. S.; Zhao, S.; Zhou, Z. Y.; Quan, T. F.; Luo, T. P. J. Am. Chem. Soc. 2016, 138, 6261. For synthetic studies toward caribenol A, see: (e) Kaloko, J. J.; Teng, Y. H. G.; Ojima, I. Chem. Commun. 2009, 45, 4569. (f) Mondal, S.; Yadav, R. N.; Ghosh, S. Tetrahedron. Lett. 2009, 50, 5277. (4) Chen, I. T.; Baitinger, I.; Schreyer, L.; Trauner, D. Org. Lett. 2014, 16, 166. (5) For our previous efforts towards caribenols A and B, see: (a) Ingrid, T. Chen, Ph.D. dissertation, University of California, Berkeley, 2011. (b) Lucas, Schreyer, M.S. dissertation, University of Vienna, 2014.
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
(6) For reviews about the allenic Pauson-Khand reaction, see: (a) Kitagaki, S.; Inagaki, F.; Mukai, C. Chem. Soc. Rev. 2014, 43, 2956. (b) Inagaki, F.; Kitagaki, S.; Mukai, C. Synlett 2011, 594. (c) Alcaide, B.; Almendros, P. Eur. J. Org. Chem. 2004, 3377. For recent synthetic applications, see: (d) Kawamura, S.; Chu, H.; Felding, J.; Baran, P. S. Nature 2016, 532, 90. (e) McKerrall, S. J.; Jørgensen, L.; Kuttruff, C. A.; Unquheuer, F.; Baran, P. S. J. Am. Chem. Soc. 2014, 136, 5799. (f) Jørgensen, L.; McKerrall, S. J. Kuttruff, C. A.; Unqeheuer, F.; Felding, J.; Baran, P. S. Science 2013, 341, 878. (g) Williams, D. R.; Shah, A. A. J. Am. Chem. Soc. 2014, 136, 8829. (h) Lv, C.; Yan, X. H.; Tu, Q.; Di, Y. T.; Yuan, C. M.; Fang, X.; Ben-David, Y.; Xia, L.; Gong, J. X.; Shen, Y. M.; Yang, Z.; Hao, X. J. Angew. Chem. Int. Ed. 2016, 55, 7539. (i) Wen, B.; Hexum, J. K.; Widen, J. C.; Harki, D. A.; Brummond, K. M. Org. Lett. 2013, 15, 2644. (j) Grillet, F.; Huang, C. F.; Brummond, K. M. Org. Lett. 2011, 13, 6304. (k) Brummond, K. M.; Gao, D. Org. Lett. 2003, 5, 3491. (7) For recent reviews about gold catalysis in total synthesis: (a) Pflästerer, D.; Hashmi, A. S. Chem. Soc. Rev. 2016, 45, 1331. (b) Dorel, R.; Echavarren, A. M. Chem. Rev. 2015, 115, 9028. (c) Zhang, Y.; Luo, T. P.; Yang, Z. Nat. Prod. Rep. 2014, 31, 489. (d) Fürstner, A. Acc. Chem. Res. 2014, 47, 925. For cycloisomerization of 1,5-enyes by gold catalysis, see: (e) Luzung, M. R.; Markham, J. P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 10858. (f) Toullec, P. Y.; Blarre, T.; Michelet, V. Org. Lett. 2009, 11, 2888. (g) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005, 127, 6962. (8) For a review about nucleophilicity in carbon-carbon bond forming reaction: Mayr, H.; Kempf, B.; Ofial. A. R. Acc. Chem. Res. 2003, 36, 66. (9) (a) Grundl, M. A.; Kaster, A.; Beaulieu, E. D.; Trauner, D. Org. Lett. 2006, 8, 5429. For synthetic applications, see: (b) Grundl, M. A.; Trauner, D. Org. Lett. 2006, 8, 23. (c) Matveenko, M.; Liang, G. X.; Lauterwasser, E. M. W.; Zubía, E.; Trauner, D. J. Am. Chem. Soc. 2012, 134, 9291. (10) We also tried copper- or iron-mediated cross coupling of the bromide or iodide compound correspongding to 7, but the yield were less than 20%. (11) (a) Movassaghi, M.; Ahmad, O. K. J. Org. Chem. 2007, 72, 1838. (b) Myers, A. G.; Zheng, B.; Movassaghi, M. J. Org. Chem. 1997, 62, 7507. (12) Matsuzawa, S.; Horiguchi, Y.; Nakamura, E.; Kuwajima, I. Tetrahedron 1989, 45, 349. (13) (a) Evans, D. A.; Trotter, B. W.; Coleman, P. J.; Côté, B.; Dias, L. C.; Rajapakse, H. A.; Tyle, A. N. Tetrahedron 1999, 55, 8671. For synthetic applications, see: (b) Evans, D. A.; Scheidt, K. A.; Downey, C. W. Org. Lett. 2001, 3, 3009. (c) Yokoshima, S.; Tokuyama, H.; Fukuyama, T. Angew. Chem. Int. Ed. 2000, 39, 4073. (14) Shimizu, T.; Osako, K.; Nakata, T. Tetrahedron. Lett. 1997, 38, 2685. (15) For synthesis of 3-methyl-2-cyclopentenone through ring closing methathesis, see: (a) De la Torre, M. C.; Deometrio, A. M.; Álvaro, E.; García, I.; Sierra, M. A. Org. Lett. 2006, 8, 593. (b) Gradl, S. N.; Kennedy-Smith, J. J.; Kim, J.; Trauner, D. Synlett. 2002, 411. (c) ref 1k. (16) (a) Laganis, E. D.; Chenard, B. L. Tetrahedron. Lett. 1984, 25, 5831. (b) For a discussion about the difficulty of vinyl triflate cleavage, see: Tsukanov, S. V.; Comins, D. L. J. Org. Chem. 2014, 79, 9074. (17) Miles, W. H.; Connell, K. B.; Ulas, G.; Tuson, H. H.; Dethoff, E. A.; Mehta, V.; Thrall, A. J. J. Org. Chem. 2010, 75, 6820. (18) Compound 22 was already reported transform to caribenol A in 2 steps. For details, see ref 3c. (19) For a recent isolated natural product that features a similar moiety, see: Tang, Y.; Xue, Y.; Du, G.; Wang, J. P.; Liu, J. J.; Sun, B.; Li, X. N.; Yao, G. M.; Luo, Z. W.; Zhang, Y. H. Angew. Chem. Int. Ed. 2016, 55, 4069. (20) For a review about Achmatowicz reaction in total synthesis, see: Ghosh, A. K.; Brindisi, M. RSC Adv. 2016, 6, 111564. (21) (a) Conrad, J. C.; Kong, J.; Laforteza, B. N.; MacMillan, D. W. C. J. Am. Chem. Soc. 2009, 131, 11640. (b) Nicolaou, K. C.; Reingruber, R.; Sarlah, D.; Brase, S. J. Am. Chem. Soc. 2009, 131, 2086. For recent synthetic applications of radical cyclization in C-C bond formation, (c) Yang, M.; Yang, X. W.; Sun, H. B.; Li, A. Angew. Chem. Int. Ed.
Page 6 of 7
2016, 55, 2851. (d) Guo, S.; Liu, J. Ma, D. Angew. Chem. Int. Ed. 2015, 54, 1298. For related oxidative cyclization method, see: (e) Ischay, M. A.; Yoon, T. P. Eur. J. Org. Chem. 2012, 3359. (f) Guo, F.; Clift, M. D.; Thomson, R. J. Eur. J. Org. Chem. 2012, 4881. (g) Redden, A.; Moeller, K. D. Org. Lett. 2011, 13, 1678. (h) Wu, H.H.; Moeller, K. D. Org. Lett. 2007, 9, 4599. (i) Mihelcic, J.; Moeller, K. D. J. Am. Chem. Soc. 2004, 126, 9106. (j) New, D. G.; Tesfai, Z.; Moeller, K. D. J. Org. Chem. 1996, 61, 1578. (k) Baran, P. S.; Richter, J. M.; Lin, D. W. Angew. Chem. Int. Ed. 2005, 44, 609. (22) With the corresponding S,S-isomer catalyst, we only obtained 29 as a mixture with d.r. 3:1 to 5:1. (23) Detail 2D NMR also measured for compound 29. (24) (a) Kolb, H. C.; Hoffmann, H. M. R. Tetrahedron 1990, 46, 5127. (b) Caddick, S.; Cheung, S.; Frost, L. M.; Khan, S.; Pairaudeau, G. Tetrahedron. Lett. 2000, 41, 6879 and refs there in. For a review on construction of cyclopentenone, see: Roche, S. P.; Aitken, D. J. Eur, J. Org. Chem. 2010, 5339. (25) For selected recent examples of intramolecular aldol reaction after furan oxidation, see: (a) Hugelshofer, C. L.; Magauer, T. J. Am. Chem. Soc. 2015, 137, 3807. (b) Kalaitzakis, D.; Triantafyllakis, M.; Alexopoulou, I.; Sofiadis, M.; Vassilikogiannakis, G. Angew. Chem. Int. Ed. 2014, 53, 13201. (c) Vassilikogiannakis, G.; Stratakis, M. Angew. Chem. Int. Ed. 2003, 42, 5465. (26) For synthetic applications of reagent 36, see: (a) Marti, C.; Carreira. E. J. Am. Chem. Soc. 2005, 127, 11505. (b) Tiefenbacher, K.; Arion, V. A.; Mulzer, J. Angew. Chem. Int. Ed. 2007, 46, 2690. (c) Zhang, Y. D.; Danishefsky, S. J. J. Am. Chem. Soc. 2010, 132, 9567. (27) (a) Van Leusen, A, M.; Oomkes, P. G. Syn. Commun. 1980, 10, 399. For synthetic applications in total synthesis, see: (b) Siler, D. A.; Mighion, J. D.; Sorensen, E. J. Angew. Chem. Int. Ed. 2014, 53, 5332. (c) Hampel, T.; Brückner, R. Org. Lett. 2009, 11, 4842. (28) For an example of a late stage oxidation of furan utilizing dimethyldioxirane (DMDO), see: (a) Chen, X. T.; Bhattacharya, S. K.; Zhou, B. S.; Gutteridge, C. E.; Pettus, T. R. R.; Danishefsky, S. J. J. Am. Chem. Soc. 1999, 121, 6563. (b) The acetone solution of DMDO (ca 0.08 to 0.1 M) was made via Taber, D. F.; DeMatteo, P. W.; Hassan, R. A. Org. Synth. 2013, 90, 350. (29) CCDC 1522398 (13), 1522399 (12), and 1522401 (40) contain the complete crystallographic data for this paper. These data can be obtained free of charge upon request from The Cambridge Crystallographic Data Centre. (30) For CN group used as a masked ketone group in synthesis, see: Shipe, W. D.; Sorensen, E. J. J. Am. Chem. Soc. 2006, 128, 7025 and refs there in. (31) To the best of our knowledge, there are only two reported examples utilizing metal salts rather than basic conditions for hydrolysis of cyanohydrins. For use AgNO3, 2,6-lutidine, see: (a) Babler, J. H.; Marcuccilli, C. J. Oblong, J. E. Syn. Commun. 1990, 20, 1831. (b) Linghu, X.; Johnson, J. S. Angew. Chem. Int. Ed. 2003, 42, 2534. For use Ni(OAc)2, see: (c) Maréchal, A. M.; Pavc, J.; Robert, A.; Grel, P. L. J. Chem. Soc. Perkin Trans.1. 1994, 2045. (32) For a recent example, see: Allen, J G.; Danishefsky, S. J. J. Am. Chem. Soc. 2001, 123, 351. (33) For protecting-group-free synthesis reviews, see: (a) Hoffmann, R. W. Synthesis 2006, 3531. (b) Young, I. S.; Baran, P. S. Nat. Chem. 2009, 1, 193. (c) Saicic, R. N. Tetrahedron 2014, 70, 8183.
ACS Paragon Plus Environment
Page 7 of 7
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
SYNOPSIS TOC (Word Style “SN_Synopsis_TOC”). If you are submitting your paper to a journal that requires a synopsis graphic and/or synopsis paragraph, see the Instructions for Authors on the journal’s homepage for a description of what needs to be provided and for the size requirements of the artwork. To format double-column figures, schemes, charts, and tables, use the following instructions: Place the insertion point where you want to change the number of columns From the Insert menu, choose Break Under Sections, choose Continuous Make sure the insertion point is in the new section. From the Format menu, choose Columns In the Number of Columns box, type 1 Choose the OK button Now your page is set up so that figures, schemes, charts, and tables can span two columns. These must appear at the top of the page. Be sure to add another section break after the table and change it back to two columns with a spacing of 0.33 in. Table 1. Example of a Double-Column Table Column 1
Column 2
Column 3
Column 4
Column 5
Column 6
Column 7
Column 8
Authors are required to submit a graphic entry for the Table of Contents (TOC) that, in conjunction with the manuscript title, should give the reader a representative idea of one of the following: A key structure, reaction, equation, concept, or theorem, etc., that is discussed in the manuscript. Consult the journal’s Instructions for Authors for TOC graphic specifications.
Insert Table of Contents artwork here Me H
Me H
Me H
H OH
OH
HO
Me H
O common building block
Me
Me
Me Me O O caribenol A
Me H
HO Me O caribenol B
ACS Paragon Plus Environment
O O
amphilectolide
