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DOI: 10.1055/s-0039-1690196
Samarium Diiodide Catalyzed Radical Cascade Cyclizations that Construct Quaternary Stereocenters
Subject Editor: David Nicewicz and Corey Stephenson
Support for this work was provided by the UK Engineering and Physical Sciences Research Council [EPSRC; EP/M005062/01 (Postdoctoral Fellowship to H.-M.H. and EPSRC Established Career Fellowship to D.J.P.)] and the EPSRC UK National EPR Facility and Service at the University of Manchester (NS/A000055/1).
Publication History
Received: 25 July 2019
Accepted after revision: 15 August 2019
Publication Date:
28 August 2019 (online)
Published as part of the Cluster 9th Pacific Symposium on Radical Chemistry
Abstract
SmI2-catalyzed radical cascade cyclizations were used to generate complex carbocyclic products bearing quaternary stereocenters with high selectivity. Bicyclic scaffolds containing four contiguous stereocenters and one quaternary stereocenter were obtained in excellent yields (up to 99%) and with high diastereocontrol by using 5 mol% of SmI2 at ambient temperature in the absence of co-reductants or additives. Mechanistic studies support a radical relay mechanism.
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Cascade cyclizations are powerful tools for the construction of complex architectures, including those found in natural products.[1] Cascades in which the mediator can be used in catalytic rather than stoichiometric amounts are particularly desirable.[2] Radical intermediates are well suited to exploitation in selective cascade processes, and the development of radical cyclization cascades, particularly catalytic radical cascades, has seen great progress in recent years.[3] The selective construction of quaternary stereocenters remains a significant challenge because of the inherent steric congestion encountered during the construction of fully substituted stereogenic centers, a problem that is exacerbated in complex molecular settings.[4] Although there are elegant approaches to the stereocontrolled construction of quaternary stereocenters,[5] the construction of such centers during catalytic radical cascade reactions is less developed.[6]
The single-electron reductant samarium diiodide (SmI2) is well-known for its ability to build complex molecular architectures.[7] In particular, SmI2-mediated cyclization cascades have been developed[8] and some of these have been used in natural product synthesis.[9] For example, SmI2 has recently been used to mediate key steps, that also construct quaternary stereocenters, in approaches to the important natural product targets (+)-pleuromutilin,[8k] (–)-maoecrystal Z,[8p] (+)-crotogoudin,[8l] and strychnine[8s] (Scheme 1A). Almost all reactions involving SmI2 require the use of superstoichiometric amounts of the reagent. Therefore, the development of radical reactions that require only catalytic amounts of SmI2 is an important goal.
The few examples of reactions that are catalytic in SmI2 employ superstoichiometric amounts of terminal reductants and additives, for example TMSOTf and TMSCl, to achieve turnover.[7h] Zinc amalgam,[10] magnesium,[11] mischmetal,[12] and electrochemistry with samarium electrodes[13] have been used to regenerate Sm(II) from Sm(III) in catalytic SmI2 systems. Unfortunately, these approaches to catalysis with SmI2 currently lack generality and are inherently limited by the fact that superstoichiometric amounts of terminal reductants and additives are required.
We recently reported a SmI2-catalyzed radical cascade cyclization that operates by radical relay[14] and that does not require superstoichiometric amounts of terminal reductant and additives.[15] Here, we describe the SmI2-catalyzed cyclization of substrates bearing trisubstituted alkene moieties that delivers complex products bearing quaternary stereocenters with high diastereocontrol (Scheme [1]B). Our approach constitutes a rare example of the catalytic construction of complex scaffolds containing quaternary stereocenters without recourse to the use of co-reductants, co-oxidants, or additives.[16]
We used the trisubstituted alkene 1a to assess the viability of forming quaternary stereocenters by using SmI2 catalysis. Under our previously optimized conditions (5 mol% SmI2, 65 °C),[15] the corresponding product 2a was obtained in 86% yield with essentially complete diastereocontrol (Table [1], entry 1). Interestingly, the product 2a could be obtained in an improved 96% isolated yield when the reaction was run at room temperature (entry 2). Lowering the catalyst loading to 3 mol% gave a 78% NMR yield of 2a, with 21% of 1a remaining (entry 3). Crucially, in the absence of SmI2, only starting material was recovered, even after prolonging the reaction time and heating (entries 4–6). To underline the radical nature of the process and to help rule out an alternative Lewis acid-mediated cyclization,[17] 1a was exposed to SmI3, either generated in situ or prepared independently; in both cases, only starting material was recovered (entries 7 and 8). Furthermore, a range of additional Lewis acids [Sm(OTf)3, Al(OTf)3, Er(OTf)3, La(OTf)3, Fe(OTf)3, Sc(OTf)3, Yb(OTf)3, and Gd(OTf)3] were screened, but only the starting material was returned in all cases (95–99% recovery).
a General conditions: Substrate 1a (0.1 mmol) in THF (4 mL, 0.025 M) under N2 was stirred at the indicated temperature. A catalytic amount of a 0.1 M solution of SmI2 in THF was then added. The reaction was quenched after 20 min.
b Determined by 1H NMR spectroscopy with 1,3,5-trimethoxybenzene as the internal standard.
c Isolated yield: >95:5 dr as determined by 1H NMR analysis of the crude product mixture.
d The reaction mixture was stirred for 18 h.
e SmI2 was exposed to O2 before addition to the reaction mixture.
Next, we examined the scope of the SmI2-catalyzed radical cascade (Scheme [2]).[18] In addition to variation of the ester groups (the formation of 2b), the catalytic process was found to tolerate the presence of fluoro (2c, 2d, 2o, and 2q), methoxy (2e, 2i, 2n, and 2p), trifluoromethyl (2f and 2r), bromo (2g), or trifluoromethoxy (2h) substituents on either the aryl group of the aryl ketone or the aryl group on the alkene. In all cases, cascade products bearing quaternary stereocenters were obtained in high yields and with high diastereocontrol. Furthermore, naphthyl (2j and 2k), thienyl (2l), benzofuryl (2m), and imidazolyl (2s) substituents were compatible with the cascade process. Given that the methyl group is one of the most common and most important structural elements in drugs,[19] it is noteworthy that the catalytic radical cascade cyclization permits the convenient assembly of complex scaffolds bearing a methyl substituent at the quaternary stereocenter (2a–s). This methyl substituent would be difficult to introduce by alternative approaches. Finally, more-hindered alkyl substituents (ethyl, propyl, or isopropyl) on the trisubstituted alkene were also tolerated, and the cascade products 2t–v were obtained with high diastereocontrol. The relative stereochemistry of the products was assigned on the basis of NOE experiments (see Supporting Information).
The SmI2-catalyzed cascade reaction can operate on larger-scale; for example, 2a was prepared on a 2 mmol scale in 94% yield and with high diastereoselectivity by using 5 mol% of SmI2 (Scheme [3]A). Furthermore, the alternative trisubstituted alkene substrate 1w underwent a SmI2-catalyzed cascade cyclization to give tetrahydrofuran 2w, an alternative scaffold bearing a quaternary stereocenter, in good yield, albeit as a mixture of diastereoisomers (Scheme [3]B). The structure of one of the diastereoisomers of 2w was confirmed by X-ray crystallographic analysis.[20]
In addition to gaining evidence against the operation of a Lewis acid-mediated process, we found that the presence of a substoichiometric or stoichiometric amount of the radical inhibitor TEMPO in reactions of 1a prevented the formation of the cascade product 2a. Further support for a radical mechanism was obtained by an EPR experiment involving the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO); the product of trapping of 3 was detected by EPR and also by HRMS (Scheme [4]A). We also monitored the color of SmI2-catalyzed cascade reactions; for example, in a reaction of 1a, the reaction mixture retained the characteristic blue color of SmI2 long after the starting material 1a had been consumed (see the Supporting Information). This result suggests that SmI2 is regenerated and that the reagent is not acting as an initiator of an electron-transfer chain process.[21] These mechanistic observations are consistent with a catalytic cycle that we previously proposed (Scheme [4]B).[15] Ketyl radical intermediate I is generated by reductive single-electron transfer (SET) from SmI2. After fragmentation, the resultant radical enolate intermediate II [22] undergoes a 5-exo-trig cyclization to give the tertiary benzylic radical III. Facile cyclization constructs the second five-membered ring and sets two further stereocenters, including the quaternary stereocenter, with high diastereoselectivity. Finally, the ketyl radical intermediate IV collapses to give product 2a and Sm(II) after reverse SET to Sm(III). We believe that the high diastereoselectivity observed in the formation of the quaternary stereocenter arises from a preference for transition structure V in which the unfavorable 1,3-steric interactions present in VI are relieved. For the cyclization of alternative trisubstituted alkene substrate 1w, which results in a 1:1 mixture of two diastereoisomeric products, we believe that the preference is less clear cut; transition structures VII and VIII both suffer from unfavorable steric interactions and consequently a mixture of two diastereoisomeric products results (Scheme [4]C).
In summary, we have developed a SmI2-catalyzed radical cascade cyclization that constructs complex scaffolds bearing four contiguous stereocenters, including a quaternary stereocenter, in high yield and with high diastereocontrol. The cascade cyclizations take place at room temperature, use 5 mol% of SmI2, and do not require superstoichiometric co-reductants or additives. Mechanistic studies support a radical relay mechanism in which Sm(II) is regenerated.
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Acknowledgment
We thank Mr. Bin Wang, Mr. Adam Brookfield, and Professor David Collison for their assistance with the EPR studies.
Supporting Information
- Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0039-1690196.
- Supporting Information
-
References and Notes
- 1a Nicolaou KC, Edmonds DJ, Bulger PG. Angew. Chem. Int. Ed. 2006; 45: 7134
- 1b Ardkhean R, Caputo DF. J, Morrow SM, Shi H, Xiong Y, Anderson EA. Chem. Soc. Rev. 2016; 45: 1557
- 1c Tietze LF. Chem. Rev. 1996; 96: 115
- 2 Delidovich I, Palkovits R. Green Chem. 2016; 18: 590
- 3a Hung K, Hu X, Maimone TJ. Nat. Prod. Rep. 2018; 35: 174
- 3b Plesniak MP, Huang H.-M, Procter DJ. Nat. Rev. Chem. 2017; 1: 0077
- 3c Kärkäs MD, Porco JA. Jr, Stephenson CR. J. Chem. Rev. 2016; 116: 9683
- 3d Sebren LJ, Devery JJ. III, Stephenson CR. J. ACS Catal. 2014; 4: 703
- 3e Zhang B, Studer A. Chem. Soc. Rev. 2015; 44: 3505
- 4 Steven A, Overman LE. Angew. Chem. Int. Ed. 2007; 46: 5488
- 5a Zeng X.-P, Cao Z.-Y, Wang Y.-H, Zhou F, Zhou J. Chem. Rev. 2016; 116: 7330
- 5b Liu Y, Han S.-J, Liu W.-B, Stoltz BM. Acc. Chem. Res. 2015; 48: 740
- 5c Quasdorf KW, Overman LE. Nature 2014; 516: 181
- 6a Murphy JJ, Bastida D, Paria S, Fagnoni M, Melchiorre P. Nature 2016; 532: 218
- 6b Müller DS, Untiedt NL, Dieskau AP, Lackner GL, Overman LE. J. Am. Chem. Soc. 2015; 137: 660
- 7a Just-Baringo X, Procter DJ. Acc. Chem. Res. 2015; 48: 1263
- 7b Szostak M, Fazakerley NJ, Parmar D, Procter DJ. Chem. Rev. 2014; 114: 5959
- 7c Szostak M, Spain M, Procter DJ. Chem. Soc. Rev. 2013; 42: 9155
- 7d Szostak M, Spain M, Parmar D, Procter DJ. Chem. Commun. 2012; 48: 330
- 7e Szostak M, Procter DJ. Angew. Chem. Int. Ed. 2012; 51: 9238
- 7f Beemelmanns C, Reissig H.-U. Chem. Soc. Rev. 2011; 40: 2199
- 7g Beemelmanns C, Reissig H.-U. Pure Appl. Chem. 2011; 83: 507
- 7h Procter DJ, Flowers RA. II, Skrydstrup T. Organic Synthesis using Samarium Diiodide: A Practical Guide . Royal Society of Chemistry; Cambridge: 2009
- 7i Flowers RA. II. Synlett 2008; 1427
- 7j Kagan HB. Tetrahedron 2003; 59: 10351
- 7k Krief A, Laval A.-M. Chem. Rev. 1999; 99: 745
- 7l Molander GA, Harris CR. Chem. Rev. 1996; 96: 307
- 8a Huang H.-M, McDouall JJ. W, Procter DJ. Angew. Chem. Int. Ed. 2018; 57: 4995
- 8b Plesniak MP, Garduño-Castro MH, Lenz P, Just-Baringo X, Procter DJ. Nat. Commun. 2018; 9: 4802
- 8c Kern N, Plesniak MP, McDouall JJ. W, Procter DJ. Nat. Chem. 2017; 9: 1198
- 8d Huang H.-M, Procter DJ. Angew. Chem. Int. Ed. 2017; 56: 14262
- 8e Huang H.-M, Procter DJ. J. Am. Chem. Soc. 2017; 139: 1661
- 8f Huang H.-M, Bonilla P, Procter DJ. Org. Biomol. Chem. 2017; 15: 4159
- 8g Ruscoe RE, Huang H, Flitsch S, Procter DJ. Chem. Eur. J. 2016; 22: 116
- 8h Huang H.-M, Procter DJ. J. Am. Chem. Soc. 2016; 138: 7770
- 8i Rao CN, Lentz D, Reissig H.-U. Angew. Chem. Int. Ed. 2015; 54: 2750
- 8j Rao CN, Bentz C, Reissig H.-U. Chem. Eur. J. 2015; 21: 15951
- 8k Fazakerley NJ, Helm MD, Procter DJ. Chem. Eur. J. 2013; 19: 6718
- 8l Breitler S, Carreira EM. Angew. Chem. Int. Ed. 2013; 52: 11168
- 8m Parmar D, Matsubara H, Price K, Spain M, Procter DJ. J. Am. Chem. Soc. 2012; 134: 12751
- 8n Sautier B, Lyons SE, Webb MR, Procter DJ. Org. Lett. 2012; 14: 146
- 8o Li Z, Nakashige M, Chain WJ. J. Am. Chem. Soc. 2011; 133: 6553
- 8p Cha JY, Yeoman JT. S, Reisman SE. J. Am. Chem. Soc. 2011; 133: 14964
- 8q Coote SC, Quenum S, Procter DJ. Org. Biomol. Chem. 2011; 9: 5104
- 8r Parmar D, Price K, Spain M, Matsubara H, Bradley PA, Procter DJ. J. Am. Chem. Soc. 2011; 133: 2418
- 8s Beemelmanns C, Reissig H.-U. Angew. Chem. Int. Ed. 2010; 49: 8021
- 8t Helm MD, Da Silva M, Sucunza D, Findley TJ. K, Procter DJ. Angew. Chem. Int. Ed. 2009; 48: 9315
- 8u Reisman SE, Ready JM, Weiss MM, Hasuoka A, Hirata M, Tamaki K, Ovaska TV, Smith CJ, Wood JL. J. Am. Chem. Soc. 2008; 130: 2087
- 9a Nicolaou KC, Ellery SP, Chen JS. Angew. Chem. Int. Ed. 2009; 48: 7140
- 9b Edmonds DJ, Johnston D, Procter DJ. Chem. Rev. 2004; 104: 3371
- 10 Corey EJ, Zheng GZ. Tetrahedron Lett. 1997; 38: 2045
- 11a Nomura R, Matsuno T, Endo T. J. Am. Chem. Soc. 1996; 118: 11666
- 11b Aspinall HC, Greeves N, Valla C. Org. Lett. 2005; 7: 1919
- 11c Ueda T, Kanomata N, Machida H. Org. Lett. 2005; 7: 2365
- 11d Maity S, Flowers RA. II. J. Am. Chem. Soc. 2019; 141: 3207
- 12a Hélion F, Namy J.-L. J. Org. Chem. 1999; 64: 2944
- 12b Lannou M.-I, Hélion F, Namy J.-L. Tetrahedron 2003; 59: 10551
- 13a Sun L, Sahloul K, Mellah M. ACS Catal. 2013; 3: 2568
- 13b Zhang YF, Mellah M. ACS Catal. 2017; 7: 8480
- 14a Huang H.-M., Garduño-Castro M. H., Morrill C., Procter D. J.; Chem. Soc. Rev.; DOI: 10.1039/c8cs00947c.
- 14b Lu Z, Shen M, Yoon TP. J. Am. Chem. Soc. 2011; 133: 1162
- 14c Amador AG, Sherbrook EM, Yoon TP. J. Am. Chem. Soc. 2016; 138: 4722
- 14d Amador AG, Sherbrook EM, Lu Z, Yoon T. Synthesis 2018; 50: 539
- 14e Hao W, Wu X, Sun JZ, Siu JC, MacMillan SN, Lin S. J. Am. Chem. Soc. 2017; 139: 12141
- 14f Hao W, Harenberg JH, Wu X, MacMillan SN, Lin S. J. Am. Chem. Soc. 2018; 140: 3514
- 14g Huang X, Lin J, Shen T, Harms K, Marchini M, Ceroni P, Meggers E. Angew. Chem. Int. Ed. 2018; 57: 5454
- 15 Huang H.-M, McDouall JJ. W, Procter DJ. Nat. Catal. 2019; 2: 211
- 16 Gansäuer A, Behlendorf M, von Laufenberg D, Fleckhaus A, Kube C, Sadasivam DV, Flowers II RA. Angew. Chem. Int. Ed. 2012; 51: 4739
- 17 Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
- 18 SmI2-Catalyzed Cyclization Cascade; General Procedure An oven-dried vial containing a stirrer bar was charged with the appropriate substrate 1 (0.1 mmol, 1 equiv) then placed under a positive pressure of N2. THF (0.025 M, 4.0 mL) was added, and the solution was stirred at r.t. Fresh SmI2 solution (typically, 5%, 0.1 M, 0.05 mL) was added and, after the specified time (typically, 20 min), the mixture was filtered through a pad of silica gel, which was washed with CH2Cl2 (3 × 5 mL). The solution was concentrated in vacuo to give product 2 typically without the need for further purification. In some cases, products required purification by chromatography (silica gel). Diethyl rac-(3aS,4S,5S,6aR)-5-Benzoyl-4-methyl-4-phenylhexahydropentalene-2,2(1H)-dicarboxylate (2a) Colorless oil; yield: 43.2 mg (96%). IR (neat): 2981, 1724, 1446, 1252, 1182, 907, 710 cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.50–7.40 (m, 2 H, ArH), 7.39–7.32 (m, 1 H, ArH), 7.28–7.10 (m, 7 H, ArH), 4.23–4.13 [m, 5 H, 2 × CH2CH3 and C(O)CH], 3.09 [dt, J = 10.9, 9.3 Hz, 1 H, CCH2CHC(Me)Ph], 2.97–2.86 (m, 1 H, CCH2CH), 2.66 (dd, J = 13.4, 7.9 Hz, 1 H, 1 H from CCH2CHCH2), 2.27 [d, J = 9.3 Hz, 2 H, CCH2CHC(Me)Ph], 2.24–2.11 (m, 2 H, CCH2CHCH2), 2.01 (dd, J = 13.3, 8.1 Hz, 1 H, 1 H from CCH2CHCH2), 1.29–1.19 (m, 9 H, 2 × CH2CH3 and CH3). 13C NMR (101 MHz, CDCl3): δ = 201.2 (C=O), 172.3 [OC(O)], 171.6 [OC(O)], 149.6 (ArCq), 137.9 (ArCq), 132.5 (ArCH), 128.4 (2 × ArCH), 128.4 (2 × ArCH), 128.1 (2 × ArCH), 126.2 (2 × ArCH), 126.1 (ArCH), 64.0 (Cq), 62.0 [C(O)CH], 61.51 (CH2CH3), 61.5 (CH2CH3), 57.4 [CCH2CHC(Me)Ph], 50.2 (Cq), 42.3 (CCH2CH), 40.1 (CCH2CHCH2), 35.5 [CCH2CHC(Me)Ph], 34.5 (CCH2CH), 19.6 (CH3), 14.2 (CH2CH3), 14.1 (CH2CH3). MS (ESI+): m/z (%): 471.2 [M + Na]+. HRMS (ESI+): m/z [M + Na]+ calcd for C28H32NaO5: 471.2142; Found: 471.2136. Diethyl rac-(3aR,4S,5S,6aS)-5-Benzoyl-4-ethyl-4-phenylhexahydropentalene- 2,2(1H)-dicarboxylate (2t) Colorless oil; yield: 44.1 mg (95%). IR (neat): 2970, 1726, 1674, 1455, 1365, 1217, 908, 762 cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.96–7.88 (m, 2 H, ArH), 7.60–7.52 (m, 1 H, ArH), 7.47 (dd, J = 8.3, 6.9 Hz, 2 H, ArH), 7.38–7.29 (m, 4 H, ArH), 7.23–7.17 (m, 1 H, ArH), 4.32–4.12 [m, 5 H, 2 × CH2CH3 and C(O)CH], 3.11 [dt, J = 12.1, 7.7 Hz, 1 H, CCH2CHC(Et)Ph], 3.03–2.87 (m, 1 H, CCH2CH), 2.74–2.56 [m, 2 H, 1 H from CCH2CHC(Et)Ph and 1 H from CCH2CHCH2], 2.48 (dd, J = 13.6, 5.1 Hz, 1 H, 1 H from CCH2CHCH2), 2.35 [ddd, J = 12.7, 7.1, 1.3 Hz, 1 H, 1 H from CCH2CHC(Et)Ph], 2.06–1.89 (m, 2 H, CCH2CHCH2), 1.71 (qd, J = 6.8, 4.2 Hz, 2 H, PhCCH2CH3), 1.29 (dt, J = 15.5, 7.1 Hz, 6 H, 2 × CH2CH3), 0.47 (t, J = 7.2 Hz, 3 H, PhCCH2CH3). 13C NMR (101 MHz, CDCl3): δ = 203.9 (C=O), 172.9 [OC(O)], 172.0 [OC(O)], 149.1 (ArCq), 139.4 (ArCq), 132.9 (ArCH), 128.7 (2 × ArCH), 128.6 (2 × ArCH), 128.5 (2 × ArCH), 126.5 (2 × ArCH), 126.0 (ArCH), 61.7 (Cq), 61.5 (CH2CH3), 61.4 (CH2CH3), 59.0 [C(O)CH], 57.9 (Cq), 51.2 [CCH2CHC(Et)Ph], 43.0 (CCH2CH), 39.3 (CCH2CHCH2), 36.1 (CCH2CH), 35.1 [CCH2CHC(Et)Ph], 28.5 (PhCCH2CH3), 14.3 (CH2CH3), 14.2 (CH2CH3), 10.6 (PhCCH2CH3). MS (ESI+): m/z (%): 485.3 [M + Na] + . HRMS (ESI + ): m/z [M + H]+ Calcd for C29H35O5: 463.2479; Found: 463.2474.
- 19 Schönherr H, Cernak T. Angew. Chem. Int. Ed. 2013; 52: 12256
- 20 CCDC 1915447 contains the supplementary crystallographic data for compound 2w. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
- 21a Studer A, Curran DP. Nat. Chem. 2014; 6: 765
- 21b Studer A, Curran DP. Angew. Chem., Int. Ed. 2016; 55: 58
- 22 For a review of the chemistry of samarium enolates, see: Rudkin IM, Miller LC, Procter DJ. Spec. Period. Rep.: Organomet. Chem. 2008; 34: 19
For reviews on the use of samarium diiodide, see:
For recent examples, see:
For a recent review of catalytic radical relays, see:
For selected examples involving ketyl radicals, see:
-
References and Notes
- 1a Nicolaou KC, Edmonds DJ, Bulger PG. Angew. Chem. Int. Ed. 2006; 45: 7134
- 1b Ardkhean R, Caputo DF. J, Morrow SM, Shi H, Xiong Y, Anderson EA. Chem. Soc. Rev. 2016; 45: 1557
- 1c Tietze LF. Chem. Rev. 1996; 96: 115
- 2 Delidovich I, Palkovits R. Green Chem. 2016; 18: 590
- 3a Hung K, Hu X, Maimone TJ. Nat. Prod. Rep. 2018; 35: 174
- 3b Plesniak MP, Huang H.-M, Procter DJ. Nat. Rev. Chem. 2017; 1: 0077
- 3c Kärkäs MD, Porco JA. Jr, Stephenson CR. J. Chem. Rev. 2016; 116: 9683
- 3d Sebren LJ, Devery JJ. III, Stephenson CR. J. ACS Catal. 2014; 4: 703
- 3e Zhang B, Studer A. Chem. Soc. Rev. 2015; 44: 3505
- 4 Steven A, Overman LE. Angew. Chem. Int. Ed. 2007; 46: 5488
- 5a Zeng X.-P, Cao Z.-Y, Wang Y.-H, Zhou F, Zhou J. Chem. Rev. 2016; 116: 7330
- 5b Liu Y, Han S.-J, Liu W.-B, Stoltz BM. Acc. Chem. Res. 2015; 48: 740
- 5c Quasdorf KW, Overman LE. Nature 2014; 516: 181
- 6a Murphy JJ, Bastida D, Paria S, Fagnoni M, Melchiorre P. Nature 2016; 532: 218
- 6b Müller DS, Untiedt NL, Dieskau AP, Lackner GL, Overman LE. J. Am. Chem. Soc. 2015; 137: 660
- 7a Just-Baringo X, Procter DJ. Acc. Chem. Res. 2015; 48: 1263
- 7b Szostak M, Fazakerley NJ, Parmar D, Procter DJ. Chem. Rev. 2014; 114: 5959
- 7c Szostak M, Spain M, Procter DJ. Chem. Soc. Rev. 2013; 42: 9155
- 7d Szostak M, Spain M, Parmar D, Procter DJ. Chem. Commun. 2012; 48: 330
- 7e Szostak M, Procter DJ. Angew. Chem. Int. Ed. 2012; 51: 9238
- 7f Beemelmanns C, Reissig H.-U. Chem. Soc. Rev. 2011; 40: 2199
- 7g Beemelmanns C, Reissig H.-U. Pure Appl. Chem. 2011; 83: 507
- 7h Procter DJ, Flowers RA. II, Skrydstrup T. Organic Synthesis using Samarium Diiodide: A Practical Guide . Royal Society of Chemistry; Cambridge: 2009
- 7i Flowers RA. II. Synlett 2008; 1427
- 7j Kagan HB. Tetrahedron 2003; 59: 10351
- 7k Krief A, Laval A.-M. Chem. Rev. 1999; 99: 745
- 7l Molander GA, Harris CR. Chem. Rev. 1996; 96: 307
- 8a Huang H.-M, McDouall JJ. W, Procter DJ. Angew. Chem. Int. Ed. 2018; 57: 4995
- 8b Plesniak MP, Garduño-Castro MH, Lenz P, Just-Baringo X, Procter DJ. Nat. Commun. 2018; 9: 4802
- 8c Kern N, Plesniak MP, McDouall JJ. W, Procter DJ. Nat. Chem. 2017; 9: 1198
- 8d Huang H.-M, Procter DJ. Angew. Chem. Int. Ed. 2017; 56: 14262
- 8e Huang H.-M, Procter DJ. J. Am. Chem. Soc. 2017; 139: 1661
- 8f Huang H.-M, Bonilla P, Procter DJ. Org. Biomol. Chem. 2017; 15: 4159
- 8g Ruscoe RE, Huang H, Flitsch S, Procter DJ. Chem. Eur. J. 2016; 22: 116
- 8h Huang H.-M, Procter DJ. J. Am. Chem. Soc. 2016; 138: 7770
- 8i Rao CN, Lentz D, Reissig H.-U. Angew. Chem. Int. Ed. 2015; 54: 2750
- 8j Rao CN, Bentz C, Reissig H.-U. Chem. Eur. J. 2015; 21: 15951
- 8k Fazakerley NJ, Helm MD, Procter DJ. Chem. Eur. J. 2013; 19: 6718
- 8l Breitler S, Carreira EM. Angew. Chem. Int. Ed. 2013; 52: 11168
- 8m Parmar D, Matsubara H, Price K, Spain M, Procter DJ. J. Am. Chem. Soc. 2012; 134: 12751
- 8n Sautier B, Lyons SE, Webb MR, Procter DJ. Org. Lett. 2012; 14: 146
- 8o Li Z, Nakashige M, Chain WJ. J. Am. Chem. Soc. 2011; 133: 6553
- 8p Cha JY, Yeoman JT. S, Reisman SE. J. Am. Chem. Soc. 2011; 133: 14964
- 8q Coote SC, Quenum S, Procter DJ. Org. Biomol. Chem. 2011; 9: 5104
- 8r Parmar D, Price K, Spain M, Matsubara H, Bradley PA, Procter DJ. J. Am. Chem. Soc. 2011; 133: 2418
- 8s Beemelmanns C, Reissig H.-U. Angew. Chem. Int. Ed. 2010; 49: 8021
- 8t Helm MD, Da Silva M, Sucunza D, Findley TJ. K, Procter DJ. Angew. Chem. Int. Ed. 2009; 48: 9315
- 8u Reisman SE, Ready JM, Weiss MM, Hasuoka A, Hirata M, Tamaki K, Ovaska TV, Smith CJ, Wood JL. J. Am. Chem. Soc. 2008; 130: 2087
- 9a Nicolaou KC, Ellery SP, Chen JS. Angew. Chem. Int. Ed. 2009; 48: 7140
- 9b Edmonds DJ, Johnston D, Procter DJ. Chem. Rev. 2004; 104: 3371
- 10 Corey EJ, Zheng GZ. Tetrahedron Lett. 1997; 38: 2045
- 11a Nomura R, Matsuno T, Endo T. J. Am. Chem. Soc. 1996; 118: 11666
- 11b Aspinall HC, Greeves N, Valla C. Org. Lett. 2005; 7: 1919
- 11c Ueda T, Kanomata N, Machida H. Org. Lett. 2005; 7: 2365
- 11d Maity S, Flowers RA. II. J. Am. Chem. Soc. 2019; 141: 3207
- 12a Hélion F, Namy J.-L. J. Org. Chem. 1999; 64: 2944
- 12b Lannou M.-I, Hélion F, Namy J.-L. Tetrahedron 2003; 59: 10551
- 13a Sun L, Sahloul K, Mellah M. ACS Catal. 2013; 3: 2568
- 13b Zhang YF, Mellah M. ACS Catal. 2017; 7: 8480
- 14a Huang H.-M., Garduño-Castro M. H., Morrill C., Procter D. J.; Chem. Soc. Rev.; DOI: 10.1039/c8cs00947c.
- 14b Lu Z, Shen M, Yoon TP. J. Am. Chem. Soc. 2011; 133: 1162
- 14c Amador AG, Sherbrook EM, Yoon TP. J. Am. Chem. Soc. 2016; 138: 4722
- 14d Amador AG, Sherbrook EM, Lu Z, Yoon T. Synthesis 2018; 50: 539
- 14e Hao W, Wu X, Sun JZ, Siu JC, MacMillan SN, Lin S. J. Am. Chem. Soc. 2017; 139: 12141
- 14f Hao W, Harenberg JH, Wu X, MacMillan SN, Lin S. J. Am. Chem. Soc. 2018; 140: 3514
- 14g Huang X, Lin J, Shen T, Harms K, Marchini M, Ceroni P, Meggers E. Angew. Chem. Int. Ed. 2018; 57: 5454
- 15 Huang H.-M, McDouall JJ. W, Procter DJ. Nat. Catal. 2019; 2: 211
- 16 Gansäuer A, Behlendorf M, von Laufenberg D, Fleckhaus A, Kube C, Sadasivam DV, Flowers II RA. Angew. Chem. Int. Ed. 2012; 51: 4739
- 17 Reissig H.-U, Zimmer R. Chem. Rev. 2003; 103: 1151
- 18 SmI2-Catalyzed Cyclization Cascade; General Procedure An oven-dried vial containing a stirrer bar was charged with the appropriate substrate 1 (0.1 mmol, 1 equiv) then placed under a positive pressure of N2. THF (0.025 M, 4.0 mL) was added, and the solution was stirred at r.t. Fresh SmI2 solution (typically, 5%, 0.1 M, 0.05 mL) was added and, after the specified time (typically, 20 min), the mixture was filtered through a pad of silica gel, which was washed with CH2Cl2 (3 × 5 mL). The solution was concentrated in vacuo to give product 2 typically without the need for further purification. In some cases, products required purification by chromatography (silica gel). Diethyl rac-(3aS,4S,5S,6aR)-5-Benzoyl-4-methyl-4-phenylhexahydropentalene-2,2(1H)-dicarboxylate (2a) Colorless oil; yield: 43.2 mg (96%). IR (neat): 2981, 1724, 1446, 1252, 1182, 907, 710 cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.50–7.40 (m, 2 H, ArH), 7.39–7.32 (m, 1 H, ArH), 7.28–7.10 (m, 7 H, ArH), 4.23–4.13 [m, 5 H, 2 × CH2CH3 and C(O)CH], 3.09 [dt, J = 10.9, 9.3 Hz, 1 H, CCH2CHC(Me)Ph], 2.97–2.86 (m, 1 H, CCH2CH), 2.66 (dd, J = 13.4, 7.9 Hz, 1 H, 1 H from CCH2CHCH2), 2.27 [d, J = 9.3 Hz, 2 H, CCH2CHC(Me)Ph], 2.24–2.11 (m, 2 H, CCH2CHCH2), 2.01 (dd, J = 13.3, 8.1 Hz, 1 H, 1 H from CCH2CHCH2), 1.29–1.19 (m, 9 H, 2 × CH2CH3 and CH3). 13C NMR (101 MHz, CDCl3): δ = 201.2 (C=O), 172.3 [OC(O)], 171.6 [OC(O)], 149.6 (ArCq), 137.9 (ArCq), 132.5 (ArCH), 128.4 (2 × ArCH), 128.4 (2 × ArCH), 128.1 (2 × ArCH), 126.2 (2 × ArCH), 126.1 (ArCH), 64.0 (Cq), 62.0 [C(O)CH], 61.51 (CH2CH3), 61.5 (CH2CH3), 57.4 [CCH2CHC(Me)Ph], 50.2 (Cq), 42.3 (CCH2CH), 40.1 (CCH2CHCH2), 35.5 [CCH2CHC(Me)Ph], 34.5 (CCH2CH), 19.6 (CH3), 14.2 (CH2CH3), 14.1 (CH2CH3). MS (ESI+): m/z (%): 471.2 [M + Na]+. HRMS (ESI+): m/z [M + Na]+ calcd for C28H32NaO5: 471.2142; Found: 471.2136. Diethyl rac-(3aR,4S,5S,6aS)-5-Benzoyl-4-ethyl-4-phenylhexahydropentalene- 2,2(1H)-dicarboxylate (2t) Colorless oil; yield: 44.1 mg (95%). IR (neat): 2970, 1726, 1674, 1455, 1365, 1217, 908, 762 cm−1. 1H NMR (400 MHz, CDCl3): δ = 7.96–7.88 (m, 2 H, ArH), 7.60–7.52 (m, 1 H, ArH), 7.47 (dd, J = 8.3, 6.9 Hz, 2 H, ArH), 7.38–7.29 (m, 4 H, ArH), 7.23–7.17 (m, 1 H, ArH), 4.32–4.12 [m, 5 H, 2 × CH2CH3 and C(O)CH], 3.11 [dt, J = 12.1, 7.7 Hz, 1 H, CCH2CHC(Et)Ph], 3.03–2.87 (m, 1 H, CCH2CH), 2.74–2.56 [m, 2 H, 1 H from CCH2CHC(Et)Ph and 1 H from CCH2CHCH2], 2.48 (dd, J = 13.6, 5.1 Hz, 1 H, 1 H from CCH2CHCH2), 2.35 [ddd, J = 12.7, 7.1, 1.3 Hz, 1 H, 1 H from CCH2CHC(Et)Ph], 2.06–1.89 (m, 2 H, CCH2CHCH2), 1.71 (qd, J = 6.8, 4.2 Hz, 2 H, PhCCH2CH3), 1.29 (dt, J = 15.5, 7.1 Hz, 6 H, 2 × CH2CH3), 0.47 (t, J = 7.2 Hz, 3 H, PhCCH2CH3). 13C NMR (101 MHz, CDCl3): δ = 203.9 (C=O), 172.9 [OC(O)], 172.0 [OC(O)], 149.1 (ArCq), 139.4 (ArCq), 132.9 (ArCH), 128.7 (2 × ArCH), 128.6 (2 × ArCH), 128.5 (2 × ArCH), 126.5 (2 × ArCH), 126.0 (ArCH), 61.7 (Cq), 61.5 (CH2CH3), 61.4 (CH2CH3), 59.0 [C(O)CH], 57.9 (Cq), 51.2 [CCH2CHC(Et)Ph], 43.0 (CCH2CH), 39.3 (CCH2CHCH2), 36.1 (CCH2CH), 35.1 [CCH2CHC(Et)Ph], 28.5 (PhCCH2CH3), 14.3 (CH2CH3), 14.2 (CH2CH3), 10.6 (PhCCH2CH3). MS (ESI+): m/z (%): 485.3 [M + Na] + . HRMS (ESI + ): m/z [M + H]+ Calcd for C29H35O5: 463.2479; Found: 463.2474.
- 19 Schönherr H, Cernak T. Angew. Chem. Int. Ed. 2013; 52: 12256
- 20 CCDC 1915447 contains the supplementary crystallographic data for compound 2w. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
- 21a Studer A, Curran DP. Nat. Chem. 2014; 6: 765
- 21b Studer A, Curran DP. Angew. Chem., Int. Ed. 2016; 55: 58
- 22 For a review of the chemistry of samarium enolates, see: Rudkin IM, Miller LC, Procter DJ. Spec. Period. Rep.: Organomet. Chem. 2008; 34: 19
For reviews on the use of samarium diiodide, see:
For recent examples, see:
For a recent review of catalytic radical relays, see:
For selected examples involving ketyl radicals, see:
