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Communication
Diastereoselective Synthesis of Seven-Membered Ring transAlkenes from Dienes and Aldehydes by Silylene Transfer Margaret A Greene, Michel Prévost, Joshua Tolopilo, and Keith A. Woerpel J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja305713v • Publication Date (Web): 11 Jul 2012 Downloaded from http://pubs.acs.org on July 16, 2012
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Journal of the American Chemical Society
Dia stereoselective S ynt hesis o f Seven-Membered Ri n g t ran s -A lkenes fr o m D ienes a nd A ldeh ydes b y Sil ylene T ra nsfer Margaret A. Greene,† Michel Prévost,‡ Joshua Tolopilo, and K. A. Woerpel* Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003 USA Supporting Information. a single diastereomer (as determined by 1H NMR ABSTRACT: Silver-catalyzed silylene transfer to alkenes spectroscopy).21 This seven-membered ring trans-alkene was formed vinylsilacyclopropanes regioselectively. These highly reactive: attempts to isolate alkene 4a led to addition allylic silanes underwent additions to aldehydes to form reactions (vide infra). Even in the absence of additional seven-membered ring trans-alkenes with high reagents, the trans-cycloalkene 4a underwent formal [1,3]diastereoselectivity. The high reactivity of the trans sigmatropic rearrangement over several hours to form an alkenes is evidenced by their formal [1,3]-sigmatropic oxasilacyclopentane (5a) that could be isolated and purified. rearrangement reactions and their rapid additions of oxygen–hydrogen bonds across the carbon–carbon double Scheme 1. One-flask synthesis of seven-membered ring bonds. trans-alkenes. t-Bu Si t-Bu 2
Me
Investigations of the chemistry of seven-membered ring trans-alkenes have been limited by the difficulty of making such highly strained alkenes. 1 The development of methods for the synthesis of seven-membered cyclic trans-alkenes should lead to useful applications of these strained compounds, considering that advances in the preparation of the larger eight- and nine-membered ring trans-alkenes have enabled these highly reactive compounds to be used in synthesis2,3,4,5 and bioconjugation.6 In contrast to the larger cyclic trans-alkenes, however, no methods have been developed for the synthesis of functionalized seven-membered ring cyclic trans-alkenes. Photo-isomerization of ciscycloheptene provides minute quantities of the trans isomer, which was unstable at –30 ˚C.7 Trapping of transient transcycloheptenes has not proven to be synthetically useful,8,9 and syntheses of seven-membered ring trans-alkenes containing heteroatoms in the ring are lengthy and not general.10,11 In this Communication, we report a one-flask synthesis of seven-membered ring trans-alkenes by regioselective, catalytic silylene transfer to a diene followed by a rapid diastereoselective addition of an aldehyde. Initial studies indicate that these strained alkenes are highly reactive. Our diastereoselective synthesis of seven-membered ring trans-alkenes was predicated on the high reactivity of strained allylic silanes with aldehydes.12,13,14,15 The preparation of the requisite allylic silane (such as 3a, Scheme 1) could be challenging because it required a formal [2+1] cycloaddition of a silylene with a diene instead of the formal [4+2] cycloaddition that is typically observed.16,17,18,19 The silvercatalyzed silylene transfer reaction to diene 1a, however, gave vinyl silacyclopropane 3a regioselectively (Scheme 1).20 After the silylene transfer reaction was complete (less than ten minutes), one equivalent of benzaldehyde was added, and within ten minutes, the allylic silane underwent quantitative insertion of an aldehyde to afford the cyclic trans-alkene 4a as
Me
AgCO2CF3 (1 mol %) 99% (NMR)
1a H PhCHO 99% (NMR)
t-Bu t-Bu Si
Me Me Ph
O t-Bu SiH t-Bu 4a
3a
Me Me
Me H Me t-Bu Si O Ph 67% (overall t-Bu 5a isolated yield) 22 ˚C
A number of seven-membered ring trans-alkenes can be synthesized using different substituted dienes and aldehydes (eq 1, Table 1). In all cases, the silylene transfer reaction was regioselective and complete in less than ten minutes, and the addition to the aldehyde was diastereoselective and rapid (less than ten minutes, except for branched alkyl aldehydes, which required three hours). Silylene transfer to (E)-1(triisopropylsiloxy)-1,3-butadiene (diene 1c) occurred at the less electron-rich double bond even though silylene transfer generally occurs to the more electron-rich alkene.22 The resulting vinylsilacyclopropane, however, reacted not as the enol ether, but as the allylic silane.15,23
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2 R1 AgCO2CF3; R2
1
R3CHO
H
R1
R2 O R3 t-Bu SiH t-Bu 4
∆
R1
t-Bu
H R2(1) t-Bu Si O R3 t-Bu 5
R1 Me H H H H
6
H
R2 Me Me OTIPS OTIPS OTIPS OTIPS
R3 Ph Ph Ph i-Pr (E)CHCHCH3 CHCH3 Ph
4 a b c d e
% 99 99 99 75 84
5 a b c d e
% 67 a 51 a 99 b 80 b 86 b
Me
H
75
f
71
a
The stereochemical configuration of the seven-membered ring trans-alkene was determined by 1H NMR spectroscopy and is consistent with the high reactivity of these compounds (vide infra). The vinyl protons of the unstable sevenmembered ring trans-alkenes couple with coupling constants ranging from J = 17.2-17.6 Hz. These values are consistent with the reported coupling constants of trans-cycloheptene measured by low temperature NMR spectroscopy (J = 18 Hz). 7 In contrast, the vinyl protons of a stable cisoxasilacycloheptene exhibit a much smaller coupling constant (J = 10.9 Hz).16 Nuclear Overhauser Effect experiments are consistent with the assignment of the alkene geometry and the overall conformational preference depicted for compounds 4: irradiation of each vinyl proton leads to NOE enhancements to substituents on opposite faces of the ring. Further evidence for the stereochemical assignment results from cleavage of the silicon–oxygen bond and isolation of the stable allylic silane 6, which exhibits coupling between the vinylic protons (J = 15.2 Hz) that is consistent with other (E)-allylic silanes.24,25 H
H
O t-Bu SiH t-Bu
OTIPS Ph 4c
n-Bu4NF; Ac2O, NEt3, DMAP
t-Bu t-Bu Si AcO
H
OAc Ph (2)
6
H
OAc
Although the seven-membered ring trans-alkene products hydrolyzed readily upon handling, they isomerized slowly to a product that could be isolated and purified (alkene 5, eq 1). This [1,3]-silyl rearrangement to a stable oxasilacyclopentene, which would be expected to require high temperatures (500 °C),26 occurred readily at room temperature in most cases. In the case of the trans-alkene derived from 3-methylpentadiene, isomerization did not occur, which is likely because this product would be sterically congested (eq 3). The half-lives for the formal [1,3]-sigmatropic rearrangement at room temperature average ten to twelve hours. The rearrangement from seven-membered ring trans-alkene to oxasilacyclopentane is likely a thermal process, because irradiation under a UV lamp (254 nm) did not accelerate the rearrangement. On the other hand, heating the trans-alkenes at 60 ˚C reduced the half-life to 30 minutes and improved its yield (Table 1). The ease of this transformation compared to known 1,3-silyl rearrangements26 provides additional confirmation that the cyclic trans-alkene is highly strained.
(3)
H
Si O t-Bu H A
b
∆ = room temperature, isolated yield. b ∆ = 60 ˚C, 1H NMR yield based on comparison to mesitylene internal standard.
Me O Ph t-Bu SiMe 8 t-Bu
H
The formation of the trans double bond in the sevenmembered ring can be explained by considering the mechanism of insertion of the aldehyde. The Lewis acidic silicon atom.12,13,27,28 of the vinylsilacyclopropane intermediate enables complexation of the aldehyde. Cyclization through closed, chair-like transition state14,15,29 A would form the observed trans double bond in the product (eq 4). t-Bu
f
Ph
Me
Table 1. Formation and rearrangement of trans-oxasilacycloheptene
entry 1 2 3 4 5
O
t-Bu Si 7
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OTIPS Ph
OTIPS O Ph (4) t-Bu SiH t-Bu B (= 4c)
The highly organized transition state for the insertion also enables the mutual kinetic resolution30 of a vinylsilacyclopropane and a chiral aldehyde. Insertion of racemic 2-phenylpropanal into the silacyclopropane derived from a silyloxydiene 1c provided trans-oxasilacycloheptene 4f as a single diastereomer (Table 1, entry 6). The X-ray crystal structure obtained after rearrangement to the oxasilacyclopentane revealed that the mutual kinetic resolution matched (S)-2-phenylpropanal with (S)-vinylsilacyclopropane 3c (and the (R)-isomers with each other). Formation of this diastereomer is consistent with Felkin–Anh addition to the aldehyde, which minimizes syn-pentane interactions31 (as shown for the (S,S)-pair in eq 5). H t-Bu
Si O H t-Bu C
Me OTIPS H Ph
H
H
Me OTIPS O (5) Si H t-Bu H Ph t-Bu D (= 4f)
Preliminary studies revealed the high reactivity of the alkenes formed by these new reactions. Attempts to purify trans-alkene 4a by silica gel chromatography resulted in the regioselective and stereoselective hydration of the double bond (Scheme 2). Acetic acid also added selectively across trans-cycloheptene 4a (Scheme 2).32 The double bond of the oxasilacyclopentane 5c also underwent a highly stereoselective reaction: when it was treated with MCPBA, a single diastereomer of the trans-fused epoxide 9 was formed (eq 6). The oxasilacyclopentane likely underwent epoxidation followed by acid-catalyzed rearrangement to the eightmembered ring trans-alkene33 then rapid epoxidation of this strained carbon–carbon double bond. Scheme 2. Reactivity of the seven-membered ring transalkene 4a.
H
Me
O t-Bu SiH t-Bu
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Me Ph 4a
H Me H Me silica gel HO O Ph t-Bu SiH 50% from diene t-Bu 9 H Me H Me 36% AcO Ph from diene t-Bu Si O H t-Bu 10 AcOH
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H t-Bu Si O t-Bu
OTIPS Ph
MCPBA
5c
O
O O Si t-Bu H t-Bu 11
OTIPS (6) Ph
In conclusion, we have developed a rapid synthesis of seven-membered ring trans-alkenes by a single-flask reaction. This process involves silylene transfer to a diene followed by diastereoselective insertion of an aldehyde into the resultant allylic silane. The highly ordered transition state of this reaction enables a chiral aldehyde to discriminate between the enantiomers of the vinyl silacyclopropane.
AS S O C IATED C ONTENT Supporting Information. Experimental procedures and characterization data, including X-ray crystallographic data. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTH O R INF O R MATI O N C orresp ond in g Auth or *Professor Keith Woerpel, Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003 USA
[email protected] Presen t Addresses †
Department of Chemistry, University of California, Irvine, CA 92697-2025 USA ‡ Institut de Recherches Cliniques de Montréal, 110 avenue des Pins Ouest, Montréal (Québec), H2W 1R7, Canada
AC KN OWLEDG MENT This research was supported by the National Institute of General Medical Sciences of the National Institutes of Health (GM-54909). A Fonds Québécois de la Recherche sur la Nature et les Technologies fellowship to M. P. is also acknowledged. We thank Dr. Phil Dennison (UCI) and Dr. Chin Lin (NYU) for assistance with NMR spectroscopy. Dr. John Greaves (UCI), Ms. S. Sorooshian (UCI), and Dr. Lin (NYU) are acknowledged for assistance with mass spectrometry. We thank Dr. Joe Ziller (UCI) and Dr. Chunhua Hu (NYU) for X-ray analysis and the Molecular Design Institute of NYU for purchasing a single crystal diffractometer. References: 1. Barrows, S. E. Eberlein, T. H. J. Chem. Ed. 2005, 30, 1334– 1339. 2. Royzen, M.; Taylor, M. T.; DeAngelis, A. Fox, J. M. Chem. Sci. 2011, 2, 2162–2165. 3. Larionov, O. V. Corey, E. J. J. Am. Chem. Soc. 2008, 130, 2954–2955. 4. Tomooka, K.; Suzuki, M.; Shimada, M.; Runyan, N. Uehara, K. Org. Lett. 2011, 13, 4926–4929. 5. Drahl, M. A.; Akhmedov, N. G. Williams, L. J. Tetrahedron Lett. 2011, 52, 325–328.
6. Taylor, M. T.; Blackman, M. L.; Dmitrenko, O. Fox, J. M. J. Am. Chem. Soc. 2012, 133, 9646–9649. 7. Squillacote, M. E.; Bergman, A. De Felippis, J. Tetrahedron Lett. 1989, 30, 6805–6808. 8. Hoffmann, R. Inoue, Y. J. Am. Chem. Soc. 1999, 121, 10702– 10710. 9. Bogen, S.; Fensterbank, L. Malacria, M. C. R. Acad. Sci. II C 2001, 4, 423–426. 10. Krebs, A.; Pforr, K.-I.; Raffay, W.; Thölke, W. A.; Hardt, I. Boese, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 159–160. 11. Shimizu, T.; Shimizu, K. Ando, W. J. Am. Chem. Soc. 1991, 113, 354–355. 12. Matsumoto, K.; Oshima, K. Utimoto, K. J. Org. Chem. 1994, 59, 7152–7155. 13. Zhang, X.; Houk, K. N. Leighton, J. L. Angew. Chem. Int. Ed. 2005, 44, 938–941. 14. Prévost, M. Woerpel, K. A. J. Am. Chem. Soc. 2009, 131, 14182–14183. 15. Ventocilla, C. C. Woerpel, K. A. J. Am. Chem. Soc. 2011, 133, 406–408. 16. Wilkinson, S. C.; Lozano, O.; Schuler, M.; Pacheco, M. C.; Salmon, R. Gouyerneur, V. Angew. Chem., Int. Ed. Engl. 2009, 48, 7083–7086. 17. Belzner, J.; Ihmels, H.; Kneisel, B. O.; Gould, R. O. HerbstIrmer, R. Organometallics 1995, 14, 305–311. 18. Gaspar, P. P.; Beatty, A. M.; Chen, T.; Haile, T.; Lei, D.; Winchester, W. R.; Braddock-Wilking, J.; Rath, N. P.; Klooster, W. T.; Koetzle, T. F.; Mason, S. A. Albinati, A. Organometallics 1999, 18, 3921–3932. 19. For examples of stable vinylsilacyclopropanes, see: Zhang, S.; Wagenseller, P. E. Conlin, R. T. J. Am. Chem. Soc. 1991, 113, 42724278. 20. These vinylsilanes were stable as long as they were protected from oxygen and water. No isomerization to silacyclopentenes, the product of a formal [4+2] cycloaddition, was observed. 21. A control experiment suggested that silver trifluoroacetate plays no role in the reaction with the aldehyde. Addition of tetramethylethylenediamine, which should complex silver (Comuzzi, C.; Novelli, R.; Portanova, R.; Tolazzi, M. Supramol. Chem. 2001, 13, 455–460), before addition of aldehyde had no impact on the insertion reaction. 22. Driver, T. G. Woerpel, K. A. J. Am. Chem. Soc. 2003, 125, 10659–10663. 23. This methodology can be employed on a preparative scale: trans-oxasilacycloheptene 4c was prepared on a 1 mmol scale during the preparation of allylic silane 6. Details are provided as Supporting Information. 24. Alberts, V.; Cuthbertson, M. J.; Hawker, D. W. Wells, P. R. Org. Magn. Resonance. 1984, 22, 556–560. 25. Acyclic (Z)-allylic silanes show coupling constants between 10.7 and 11.0 Hz, whereas (E)-allylic silanes exhibit coupling constants between 14.9 and 15.2 Hz: see Smitrovich, J. H. Woerpel, K. A. J. Org. Chem. 2000, 65, 1601–1614. 26. Slutsky, J. Kwart, H. J. Am. Chem. Soc. 1973, 95, 8678–8685. 27. Denmark, S. E.; Jacobs, R. T.; Dai-Ho, G. Wilson, S. Organometallics 1990, 9. 28. Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X. Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920–7921. 29. Zimmerman, H. E. Traxler, M. D. J. Am. Chem. Soc. 1957, 79, 1920–1923. 30. Tomo, Y. Yamamoto, K. Tetrahedron Lett. 1985, 26, 1061– 1064. 31. Roush, W. R. J. Org. Chem. 1991, 56, 4151–4157. 32. Acetic acid does not add to allylic silanes: Suslova, E. N.; Albanov, A. I. Shainyan, B. A. J. Organomet. Chem. 2009, 694, 420–426.
33. Tanino, K.; Yoshitani, N.; Moriyama, F. Kuwajima, I. J. Org. Chem. 1997, 62, 4206–4207.
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Table of Contents Graphic Si
R1 R2
t-Bu t-Bu
AgCO2CF3; R3CHO
H
R1
O t-Bu SiH t-Bu
R2 R3
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