Letter pubs.acs.org/OrgLett
Highly Regio‑, Diastereo‑, and Enantioselective Rhodium-Catalyzed Intramolecular Cyclopropanation of (Z)‑1,3-Dienyl Aryldiazoacetates Kostiantyn O. Marichev, Justin T. Ramey, Hadi Arman, and Michael P. Doyle* Department of Chemistry, The University of Texas at San Antonio, San Antonio, Texas 78249, United States S Supporting Information *
ABSTRACT: Chiral cyclopenta[2,3]cyclopropa[1,2-c]pyran-4-ones have been synthesized via dirhodium(II)-catalyzed intramolecular cyclopropanation of (Z)-1,3-dienyl aryldiazoacetates. High regio-, diastereo-, and enantiocontrol were achieved using chiral dirhodium 2-phthalimide carboxylates. Preferential addition occurs at the 3,4- rather than the 1,2-double bond with the chiral dirhodium catalysts, although both outcomes occur with other transition-metal catalysts.
T
Scheme 1. Divergent Outcomes of the Intramolecular Metal−Carbene Reaction of (Z)-1,3-Dienyl Aryldiazoacetates
he formation of cyclopropane compounds by metalcatalyzed reactions of diazo compounds with alkenes is a classic reaction in organic chemistry,1 and this transformation was one of the first to lay the foundation of catalytic asymmetric synthesis.2 Today, many chiral catalysts are able to achieve high stereocontrol for cyclopropanation of alkenes by diazo compounds.3 However, the vast majority of these reactions are performed with monoalkenes, and there are few reported examples for cyclopropanation of dienes4 and even fewer that occur intramolecularly. 5 The intramolecular reactions are commonly performed on a specific CC bond suitable for the formation of a bicyclo[n.1.0]alkane, where n can be as high as 20.6 Although electronic control is reported to determine regioselectivity in intramolecular reactions with dienes,7 this judgment is based on results from intermolecular reactions since examples where intramolecular addition occurs to both of the diene’s two double bonds is, to our knowledge, unknown. We recently discovered convenient access to 1,3dienyl carboxylates in which the carboxylate could be an aryldiazoacetate.8 Gold-catalyzed 1,3-acyloxy migration of propargylic carboxylates forms 1,3-dienes from propargylic esters through a gold(I)-catalyzed 1,3-migratory cascade involving allene intermediates.9 1-Alkoxy-1,3-butadienes undergo preferential cyclopropanation at the 3,4-double bond, but regioselectivity in these cyclopropanation reactions is catalyst dependent.4a,g If, instead of a 1-alkoxy group, a phenyldiazoacetate is at the 1-position, one can expect lower regiocontrol for addition to the 3,4double bond with significant competition from electrophilic metal carbene addition to the 2-position resulting in either cyclopropanation or ylide formation to form a butenolide (Scheme 1). Having convenient access to (Z)-1-phenyl-1,3© XXXX American Chemical Society
butadienyl phenyldiazoacetates,10 we have investigated selectivity in their catalytic intramolecular cyclopropanation reactions. We now report that, although significant competition exists from the reaction occurring at the 1,2-double bond, exclusive addition can be made to occur at the 3,4-double bond in high yield and exceptional stereocontrol. We began our investigation using (Z)-2-(cyclopent-1-en-1yl)-1-phenylvinyl 2-diazo-2-phenylacetate (1a)10 (eq 1) that was conveniently formed from the corresponding 3-phenylpropargyl phenyldiazoacetate in 55% yield. Treatment of 1a with 1 mol % of dirhodium tetraacetate in dichloromethane at room temperature resulted in the formation of products (eq 1) from both of the pathways that are described in Scheme 1. Addition to the 1,2- and 3,4-double bonds resulted in butenolide 3a and two diastereomeric cyclopropanation Received: January 12, 2017
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DOI: 10.1021/acs.orglett.7b00119 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
selectivity. However, the use of the cationic gold(I) catalyst Au(JohnPhos)(MeCN)SbF6 provided 2a-syn with comparatively exceptional regio- and diastereocontrol. Chiral dirhodium tetracarboxylate catalysts 4−511 (Table 2) provided very high regioselectivity for the formation of 2a, products (2a-syn/2a-anti = 86:14), respectively, in 90% combined yield, and the ratio of 2a/3a was 67:33. The major diastereoisomer of 2a was determined to be 2a-syn by X-ray crystallography (Figure 1). In an attempt to better control
Table 2. Chiral Rhodium Catalyst Influence on Regio- and Stereocontrol for the Intramolecular Cyclopropanation of 1a (Yield (%) of 2a, 3a, dr 2a-syn/2a-anti, and % ee 2a-syn)
Figure 1. Absolute configuration of enantioenriched 2a-syn (96% ee) obtained using catalyst 4c (Table 2). X-ray crystal structure with 50% thermal ellipsoid probability.
regioselectivity and diastereoselectivity, this reaction was performed by adding 1a to the catalyst at −78 °C and then warming the reaction solution to room temperature to produce improved results in the three products (93% isolated yield) with 2a/3a = 69:31 and 2a-syn/2a-anti = 92:8 (Table 1, entry 1).
entrya catalyst 9 10 11 12 13 14 15 16 17 18f 19f 20f 21f
Table 1. Catalyst Influence on Regio- and Diastereoselectivity for the Intramolecular Cyclopropanation of 1a (Yield (%) of 2a + 3a, 2a/3a, and dr 2a-syn/2a-anti) entry
catalyst
yield of 2a + 3ab (%)
1 2 3 4 5e 6 7f 8f
Rh2(OAc)4 Rh2(oct)4 Rh2(piv)4 Rh2(pfb)4 Rh2(cap)4 Au(JohnPhos)(MeCN)SbF6 Cu(OTf)2 CuOTf·1/2Tol
93 96 94 91 88 93 45 53
a
c
2a/3a
69:31 64:36 74:26 58:42 82:18 95:5 73:27 34:66
dr of 2a (syn/ anti)d 92:8 >20:1 >20:1 88:12 87:13 >20:1 89:11 84:16
4a 4b 4c 4d 4e 4f 4g 5a 5b 6 7a 7b 7c
yield of 2ab (%)
yield of 3ac (%)
dr of 2a (syn/anti)d
ee of 2a-syne (%)
89 93 92 93 82 85 92 90 91 57 48 45 52
20:1 >20:1 83:17 85:15 85:15 75:25
83 94 96 75 44 91 84 −76 −60 −2 −13 84 40
a
Reactions were performed as reported in Table 1. bIsolated yields obtained after column chromatography. cYields estimated by 1H NMR of reaction mixtures with 1,3,5-trimethoxybenzene as the internal standard. d Calculated from 1 H NMR of reaction mixtures. e Determined by HPLC using a chiral column. fReactions and addition of 1a were carried out at 20 °C in DCE for 24 h.
a
Reactions were performed on 0.10 mmol of 1a with a temperature gradient of −78 to +20 °C. Compound 1a in 0.6 mL of DCM was added to the mixture of catalyst (1.0 mol % of Rh or 5.0 mol % of Au or Cu, and 4 Å MS (80 mg) in 0.4 mL of DCM at −78 °C within 10 min; the reaction mixture was allowed to warm to 20 °C over 1 h and then stirred for 5 h. bIsolated yields obtained after column chromatography. cRatios of 2a/3a estimated by 1H NMR analysis of reaction mixtures. dCalculated from 1H NMR spectra of reaction mixtures by ratios of the integral intensities of their olefinic C−H proton. eReactions were carried out at 20 °C in DCE for 24 h (for more examples, see the Supporting Information). fReaction time 12 h, conversion 65% (entry 7) and 69% (entry 8).
excellent diastereocontrol, and high to excellent enantiocontrol. Changing substituents in the Hashimoto-type catalysts 4 does influence enantioselectivity, but has almost no effect on yields and diastereoselectivity in the formation of 2a. The highest enantioselectivity (96% ee) was achieved using a new catalyst (4c) from an unnatural amino acid having an n-butyl substituent in the α-position of the carboxylate Rh2(SPTNB)4. A similar result (94% ee) was provided by catalyst 4b, Rh2(S-PTV)4, that has an isopropyl substituent. However, Hashimoto catalysts with smaller or larger appendages (entries 9, 12−15, Table 2) gave lower enantioselectivities. Interestingly, prolinate ligated dirhodium carboxylates Rh2(S-BSP)4 (5a) and Rh2(S-DOSP)4 (5b), also having the S-configuration, led to the opposite enantiomer of 2a (entries 16 and 17) with moderate enantioselectivity. Chiral dirhodium carboxamidates 6 and 7 were much less reactive than the chiral carboxylates and showed lower diastereoselectivity and, surprisingly,12 generally low enantioselectivities (entries 18, 19, and 21), and they were surprisingly unselective toward the formation of either 2a or 3a
The influence of other catalysts that are commonly used for intramolecular cyclopropanation reactions of diazoacetates was also assessed (Table 1). Dirhodium catalysis provided much higher product yields than did copper catalysts, and there was increased diastereocontrol using Rh2(oct)4 or Rh2(piv)4, but limited influence of carboxylate ligands on regiocontrol. Copper catalysts gave lower product yields and no improvement in B
DOI: 10.1021/acs.orglett.7b00119 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters (ratio 2a/3a nearly 1:1). Among the chiral dirhodium(II) carboxamidates, only Rh2(4S-BNOX)4 (7b) showed high enantioselectivity (84% ee) for 2a (entry 20), but with minimum regioselectivity (2a/3a = 46:54) and only moderate diastereocontrol in 2a (dr 85:15). Solvent influences had a dramatic effect on both regio- and enantioselectivies for reactions performed with Rh2(S-PTNB)4 (4c, Table 3). However, although hydrocarbon solvents are
Scheme 2. Substrate Scope for Enantioselective Cyclopropanation of 1 Catalyzed by Rh2(S-PTNB)4 (4c)a,b
Table 3. Solvent Screening for the Intramolecular Cyclopropanation of 1a Catalyzed by 4c entrya
solvent
yield of 2a (%)
yield of 3a (%)
dr of 2a (syn/anti)
ee of 2asyn (%)
1 2 3 4 5 6 7 8b
DCM DCE chloroform toluene THF diethyl ether acetonitrile cyclohexane
92 88 76 83 74 42 70 35
20:1 >20:1 >20:1 88:12 87:13 90:10
96 84 74 62 37 −12 58 26
a
Reaction conditions as reported in Table 1. bConversion 55%.
generally reported to give the highest enantioselectivities,13 reactions of 1a performed in dichloromethane provided optimum results. We anticipated that access to butenolide 3a would be enhanced in polar solvents, but no obvious correlation between regiocontrol and solvent polarity was observed. Having obtained the optimum conditions for asymmetric cyclopropanation, we investigated the substrate scope of this reaction with variation of aryldiazoacetate substituents (Ar1), aromatic substituents on the α-position of the ester (Ar2), and substituents on the terminal double bond (R1, R2) (Scheme 2). In all cases regiocontrol and diastereoselectivity were complete for the formation of syn-2, and product yields were mostly greater than 90%. However, enantioselectivities varied with the substituent from 99% ee with compound syn-2f having an electron-donating methoxy group to 54% ee with syn-2e having the electron-withdrawing nitro group. Substituent effects in Ar2 had a comparable influence on enantioselectivity, and both product yields (85−91%) and diastereoselectivies (>20:1) were high. Pure tricyclic 2l was prepared on a gram scale in 77% isolated yield with the same % ee as that reported in Scheme 2. Changing from the cyclopentenyl system 1a to the structurally simpler 1-phenyl-3-methyl-1,3-butadienyl phenyldiazoacetate (1n) had a significant effect to enantioselectivity; compound 2n was obtained with very low enantioselectivity (4% ee), although in high yield (86%) and with excellent diastereocontrol (dr >20:1). With the cyclohexyl instead of the cyclopentyl ring (1o → 2o), enantioselectivity was also low (60% ee), although 2o was formed in 83% yield and dr >20:1. We were interested to determine if tricyclic products 2 could undergo transformations to form other classes of cyclic compounds. Compound (4aR,4bR,7aS)-2a with 96% ee undergoes simple alkaline hydrolysis with lactone ring opening to form the bicyclic ketocarboxylic acid (4aR,4bR,7aS)-8 in 98% yield (Scheme 3). Classical hydrogenation using palladium on carbon under 1 atm of dihydrogen gave not only carbon− carbon double bond reduction but also ring opening of 2a with the formation of bicyclic carboxylic acid (4aR,4bR,7aS)-9 in quantitative yield. Both 8 and 9 retain the bicyclo[3.1.0]hexane
a
Isolated yields obtained after column chromatography. bdr >20:1 unless otherwise noted.
Scheme 3. Transformations of Tricyclic System 2a to Bicyclic 8 and 9 with Retention of Stereocentersa−c
a Reported are isolated yields. bRetention of stereocenters and enantiopurity were determined by HPLC using a chiral column. cXray crystal structures with 50% thermal ellipsoid probability are reported for racemic 8 and 9 and represent the relative configuration.
structure, which is a common structural unit in a variety of natural products.14 In conclusion, we have disclosed very high selectivity for intramolecular cyclopropanation of (Z)-1,3-dienyl aryldiazoacetates 1 with the use of a new phthalimide-carboxylate ligated dirhodium catalyst. Although competition exists between cyclopropanation of the 3,4-double bond and addition to the 1,2-double bond that results in the formation of butenolide product 3a with achiral dirhodium and copper catalysts and chiral dirhodium carboxamidates, only cyclopropanation occurs in reactions catalyzed by chiral dirhodium carboxylates. Solvent effects on these reactions are appreciable, as are seemingly minor changes in substituents on the 3- and 4-positions of the C
DOI: 10.1021/acs.orglett.7b00119 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
Chem. Soc. 2009, 131, 7230. (m) Kubilay, H. N.; Gungor, F. S.; Anac, O. Helv. Chim. Acta 2015, 98, 1245. (5) Representative examples of intramolecular cyclopropanation of dienes: (a) Hudlicky, T.; Kwart, L. D.; Tiedje, M. H.; Ranu, B. C.; Short, R. P.; Frazier, J. O.; Rigby, H. L. Synthesis 1986, 1986, 716. (b) Piers, E.; Jung, G. L.; Ruediger, E. H. Can. J. Chem. 1987, 65, 670. (c) Davies, H. M. L. Tetrahedron 1993, 49, 5203. (d) Davies, H. M. L.; Doan, B. D. Tetrahedron Lett. 1996, 37, 3967. (e) Doyle, M. P.; Chapman, B. J.; Hu, W.; Peterson, C. S. Org. Lett. 1999, 1, 1327. (f) Davies, H. M. L.; Calvo, R. L.; Townsend, R. J.; Ren, P.; Churchill, R. M. J. Org. Chem. 2000, 65, 4261. (g) Xu, X.; Lu, H.; Ruppel, J. V.; Cui, X.; Lopez de Mesa, S.; Wojtas, L.; Zhang, X. P. J. Am. Chem. Soc. 2011, 133, 15292. (6) Doyle, M. P.; Hu, W.; Chapman, B.; Marnett, A. B.; Peterson, C. S.; Vitale, J. P.; Stanley, S. A. J. Am. Chem. Soc. 2000, 122, 5718. (7) Doyle, M. P. Chem. Rev. 1986, 86, 919. (8) Qiu, H.; Srinivas, H. D.; Zavalij, P. Y.; Doyle, M. P. J. Am. Chem. Soc. 2016, 138, 1808. (9) Wang, Y.-M.; Lackner, A. D.; Toste, F. D. Acc. Chem. Res. 2014, 47, 889. (10) These reactants were prepared in one step from arylpropargyl aryldiazoacetates at 20 °C in 18−60% yield using Au(Me2S)Cl (5 mol %) as the catalyst and 4-chloropyridine N-oxide as an additive. For details, see the Supporting Information and ref 8. (11) For references on the preparation of chiral catalysts, see the Supporting Information. (12) These catalysts have provided the highest levels of enantiocontrol in intramolecular cyclopropanation reactions of allyl and homoallyl diazoacetates: Doyle, M. P.; Austin, R. E.; Bailey, A. S.; Dwyer, M. P.; Dyatkin, A. B.; Kalinin, A. V.; Kwan, M. M. Y.; Liras, S.; Oalmann, C. J.; Pieters, R. J.; Protopopova, M. N.; Raab, C. E.; Roos, G. H. P.; Zhou, Q.-L.; Martin, S. F. J. Am. Chem. Soc. 1995, 117, 5763. (13) Wang, H.; Guptill, D. M.; Varela-Alvarez, A.; Musaev, D. G.; Davies, H. M. L. Chem. Sci. 2013, 4, 2844. (14) (a) Joshi, B. S.; Kamat, V. N.; Pelletier, S. W.; Go, K.; Bhandary, K. Tetrahedron Lett. 1985, 26, 1273. (b) Su, W.-C.; Fang, J.-M.; Cheng, Y.-S. Phytochemistry 1993, 34, 779. (c) Magauer, T.; Mulzer, J.; Tiefenbacher, K. Org. Lett. 2009, 11, 5306. (d) Yuan, C.; Du, B.; Yang, L.; Liu, B. J. Am. Chem. Soc. 2013, 135, 9291. (e) Zhao, J.-J.; Guo, Y.Q.; Yang, D.-P.; Xue, X.; Liu, Q.; Zhu, L.-P.; Yin, S.; Zhao, Z.-M. J. Nat. Prod. 2016, 79, 2257. (f) Wang, P.; Li, R.-J.; Liu, R.-H.; Jian, K.-L.; Yang, M.-H.; Yang, L.; Kong, L.-Y.; Luo, J. Org. Lett. 2016, 18, 832.
diene. Tricyclic 2a has been converted to bicyclo[3.1.0]hexane derivatives 8 and 9 in very high yields.
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b00119. Experimental procedures, results from surveys of yields and selectivities for reaction optimizations, spectroscopic data for all new compounds, and HPLC traces for racemic and enantioenriched compounds (PDF) X-ray data for (4aR,4bR,7aS)-2a (CIF) X-ray data for rac-8 (CIF) X-ray data for rac-9 (CIF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Michael P. Doyle: 0000-0003-1386-3780 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS Support for this research from the National Science Foundation (CHE−1464690) is gratefully acknowledged. REFERENCES
(1) (a) Doyle, M. P.; McKervey, M. A.; Ye, T. In Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides; Wiley: New York, 1998. (b) Roy, M.-N.; Lindsay, V. N. G.; Charette, A. B. Stereoselective Synthesis: Reactions of Carbon− Carbon Double Bonds (Science of Synthesis); de Vries, J. G., Ed.; Thieme: Stuttgart, 2011; Vol. 1, Chapter 1.14, p 731. (2) Nozaki, H.; Moriuti, S.; Takaya, H.; Noyori, R. Tetrahedron Lett. 1966, 7, 5239. (3) (a) Doyle, M. P.; Eismont, M. Y.; Protopopova, M. N.; Kwan, M. M. Y. Tetrahedron 1994, 50, 1665. (b) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. Rev. 2003, 103, 977. (c) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev. 2003, 103, 2861. (d) Doyle, M. P. J. Org. Chem. 2006, 71, 9253. (e) Pellissier, H. Tetrahedron 2008, 64, 7041. (f) Doyle, M. P. Angew. Chem., Int. Ed. 2009, 48, 850. (g) Xu, X.; Zhu, S.-F.; Cui, X.; Wojtas, L.; Zhang, X. P. Angew. Chem., Int. Ed. 2013, 52, 11857. (h) Qian, D.; Zhang, J. Chem. Soc. Rev. 2015, 44, 677. (i) Chanthamath, S.; Iwasa, S. Acc. Chem. Res. 2016, 49, 2080. (4) Representative examples of intermolecular cyclopropanation of dienes: (a) Doyle, M. P.; Dorow, R. L.; Tamblyn, W. H.; Buhro, W. E. Tetrahedron Lett. 1982, 23, 2261. (b) Anciaux, A. J.; Demonceau, A.; Noels, A. F.; Warin, R.; Hubert, A. J.; Teyssié, P. Tetrahedron 1983, 39, 2169. (c) Doyle, M.; Dorow, R.; Buhro, W.; Griffin, J.; Tamblyn, W.; Trudell, M. Organometallics 1984, 3, 44. (d) Davies, H. M. L.; Doan, B. D. J. Org. Chem. 1998, 63, 657. (e) Davies, H. M. L.; Stafford, D. G.; Doan, B. D.; Houser, J. H. J. Am. Chem. Soc. 1998, 120, 3326. (f) Davies, H. M. L.; Venkataramani, C. Org. Lett. 2003, 5, 1403. (g) Hahn, N. D.; Nieger, M.; Dötz, K. H. Eur. J. Org. Chem. 2004, 2004, 1049. (h) Marti, C.; Carreira, E. M. J. Am. Chem. Soc. 2005, 127, 11505. (i) Itagaki, M.; Masumoto, K.; Suenobu, K.; Yamamoto, Y. Org. Process Res. Dev. 2006, 10, 245. (j) Olson, J. P.; Davies, H. M. L. Org. Lett. 2008, 10, 573. (k) Schwartz, B. D.; Denton, J. R.; Lian, Y.; Davies, H. M. L.; Williams, C. M. J. Am. Chem. Soc. 2009, 131, 8329. (l) DeAngelis, A.; Dmitrenko, O.; Yap, G. P. A.; Fox, J. M. J. Am. D
DOI: 10.1021/acs.orglett.7b00119 Org. Lett. XXXX, XXX, XXX−XXX
