Synthesis of cyclopropanes
A general cobalt-catalyzed cross-coupling between alkyl iodides and cyclopropyl, cyclobutyl, and alkenyl Grignard reagents enables an introduction of strained rings on a large panel of primary and secondary alkyl iodides. The catalytic system is simple and nonexpensive, and the reaction is chemoselective and diastereoconvergent.
C. Andersen, V. Ferey, M. Daumas, P. Bernardelli, A. Guérinot, J. Cossy, Org. Lett., 2019, 21, 2285-2289.
Suitable conditions enable the Suzuki-Miyaura coupling reaction of potassium cyclopropyl- and cyclobutyltrifluoroborates in moderate to excellent yield with electron-rich, electron-poor, and hindered aryl chlorides to give various substituted aryl cyclopropanes and cyclobutanes.
G. A. Molander, P. E. Gormisky, J. Org. Chem., 2008, 73, 7481-7485.
The Pd-catalyzed cross-coupling of aryl bromides or triflates with cyclopropylmagnesium bromide in the presence of substoichiometric amounts of zinc bromide produces cyclopropyl arenes in very good yields. The cross-coupling of other alkyl, cycloalkyl, and aryl Grignard reagents with aryl bromides under the same conditions gives the corresponding substituted arenes in good yields.
C. Shu, K. Sidhu, L. Zhang, X.-j. Wang, D. Krishnamurthy, C. H. Senanayake, J. Org. Chem., 2010, 75, 6677-6680.
The palladium-catalyzed cross-coupling reaction of tricyclopropylbismuth with aryl and heterocyclic halides and triflates tolerates numerous functional groups and does not require anhydrous conditions. The method was successfully extended to the cross-coupling of triethylbismuth.
A. Gagnon, M. Duplessis, P. Alsabeh, F. Barabé, J. Org. Chem., 2008, 73, 3452-3459.
An intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives provides a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions.
A. B. Sanford, T. A. Thane, T. M. MgGinnis, P.-P. Chen, X. Hong, E. R. Jarvo, J. Am. Chem. Soc., 2020, 142, 5017-5023.
An annulation process for the construction of 1,1-disubstituted cyclopropanes via a radical/polar crossover process proceeds by the addition of a photocatalytically generated radical to a homoallylic tosylate followed by a reduction of the intermediate radical adduct to an anion that undergoes an intramolecular substitution. The process displays excellent functional group tolerance and occurs under mild conditions with visible light irradiation.
J. A. Milligan, J. P. Phelan, V. C. Polites, C. B. Kelly, G. A. Molander, Org. Lett., 2018, 20, 6840-6844.
An intramolecular coupling of two C-H bonds on gem-dialkyl groups is accessible using aryl bromide or triflate precursors and the 1,4-Pd shift mechanism. The use of pivalate as the base was found to be crucial to divert the mechanistic pathway toward the cyclopropane instead of the previously obtained benzocyclobutene product.
A. Clemenceau, P. Thesmar, M. Gicquel, A. Le Flohic, O. Baudoin, J. Am. Chem. Soc., 2020, 142, 15355-15361.
The use of the benchtop stable triethylammonium bis(catecholato)iodomethylsilicate as bifunctional reagent in combination with an organic photocatalyst and visible light enables a cyclopropanation of an array of olefins, including trifluoromethyl- and pinacolatoboryl-substituted alkenes in a matter of hours. The reaction is highly tolerant of traditionally reactive functional groups (carboxylic acids, basic heterocycles, alkyl halides, etc.).
J. P. Phelan, S. B. Lang, J. S. Compton, C. B. Kelly, R. Dykstra, O. Gutierrez, G. A. Molander, J. Am. Chem. Soc., 2018, 140, 8037-8047.
A phosphate carbenoid (BuO)2P(O)OZnCH2I undergoes very slow degradation in solution and can be stored for several weeks at -20°C. Its reactivity was tested with cyclopropanation of alkenes, chain extension of 1,3-diketones and [2,3]-sigmatropic rearrangement reactions.
A. Voituriez, L. E. Zimmer, A. B. Charette, J. Org. Chem., 2010, 75, 1244-1250.
A class of zinc reagents (RXZnCH2Y) is very effective for the cyclopropanation of olefins. The reactivity and selectivity of these reagents can be regulated by tuning the electronic and steric nature of the RX group. A reasonable level of enantioselectivity was obtained for the cyclopropanation of unfunctionalized olefins with chiral (iodomethyl)zinc species.
J. C. Lorenz, J. Long, Z. Yang, S. Xue, X. Xie, Y. Shi, J. Org. Chem., 2004, 69, 327-334.
A mild, room temperature palladium-catalyzed cross-coupling of aromatic and heteroaromatic halides with Reformatsky reagents derived from 1-bromocyclopropanecarboxylates provides α-arylated products. The method tolerates a broad range of functionalities and dramatically shortens many of the existing routes to access widely used 1,1-disubstituted cyclopropanecarboxylate derivatives.
S. N. Greszler, G. T. Halvorsen, E. A. Voight, Org. Lett., 2017, 19, 2490-2493.
An oxidative ring contraction of easily accessible cyclobutene derivatives enables a selective formation of cyclopropylketones in the presence of mCPBA as oxidant. This functional group tolerant transformation proceeds under mild conditions at room temperature.
A. N. Baumann, F. Schüppel, M. Eisold, A. Kreppel, R. de Vivie-Riedle, D. Didier, J. Org. Chem., 2018, 83, 4905-4921.
A Rh(III)-catalyzed diastereoselective [2+1] annulation of allylic alcohols with N-enoxyphthalimides provides substituted cyclopropyl-ketones. Notably, the traceless oxyphthalimide handle serves three functions: directing C-H activation, oxidation of Rh(III), and controlling diastereoselectivity collectively with the allylic alcohol.
E. J. T. Phipps, T. Rovis, J. Am. Chem. Soc., 2019, 141, 6808-6811.
In diastereoselective cyclopropanation of alkenes with N-enoxyphthalimides through rhodium(III) catalysis, a switch from trans- to cis-diastereoinduction is attributed to a mechanistic dichotomy. Selectivity might be determined by the flexibility of rhodacyclic intermediates derived from ring-opened versus -unopened phthalimides.
T. Piou, F. Romanov-Michailidis, M. A. Ashley, M. Romanov-Michailidis, T. Rovis, J. Am. Chem. Soc., 2018, 140, 9587-9593.
Treatment of aromatic aldehydes with cyclopropenes under mild NHC-catalyzed conditions affords valuable acylcyclopropanes in moderate to high yields with an excellent level of diastereocontrol. Preliminary mechanistic studies suggest that product formation occurs via a concerted syn hydroacylation pathway.
X. Bugaut, F. Liu, F. Glorius, J. Am. Chem. Soc., 2011, 133, 8130-8133.
A tandem reaction consisting of a Wittig reaction-ring contraction process between α-hydroxycyclobutanone and phosphonium ylides provides highly functionalized cyclopropanecarbaldehydes in very good yield.
F. Cuccu, L. Serusi, A. Luridiana, F. Secci, P. Caboni, D. J. Aitken, A. Frongia, Org. Lett., 2019, 21, 7755-7758.
A highly diastereoselective addition of terminal alkynes to unsymmetrical gem-disubstituted cyclopropenes to give alkynylcyclopropanes in good to excellent yields is catalyzed by the Herrmann-Beller phosphapalladacycle. The stereofacial discrimination at the approach of the bulky alkynylpalladium species is believed to be responsible for the diastereoselectivity control of the addition reaction.
A. Tenaglia, K. Le Jeune, L. Giordano, G. Buono, Org. Lett., 2011, 13, 636-639.
N-Sulfonyl 1,2,3-triazoles readily form rhodium(II) azavinyl carbenes, which react with olefins to produce cyclopropane derivatives in high yield with excellent diastereo- and enantioselectivity.
S. Chuprakov, S. W. Kwok, L. Zhang, L. Lercher, V. V. Fokin, J. Am. Chem. Soc., 2009, 131, 18034-18035.
Optically active cis-cyclopropane carboxylates can be prepared via a Rh2(S-PTAD)4-catalyzed cyclopropanation of α-silyl styrenes with aryl diazoacetates followed by desilylation of the resulting silyl cyclopropane carboxylates.
Y. Su, Q.-F. Li, Y.-M. Zhao, P. Gu, Org. Lett., 2016, 18, 4356-4359.
A mixture of ZnI2, EtZnIˇ2OEt2 and CHI3 produces a gem-dizinc carbenoid that is an efficient cyclopropanating reagent, which shortens reaction times and leads to cleaner reactions, particularly with less reactive substrates. Mechanistic aspects of the reaction are discussed.
J.-F. Fournier, A. B. Charette, Eur. J. Org. Chem., 2004, 1401-1404.
A new class of anionic, boron-bridged analogues of the box ligands was developed. These borabox ligands showed a considerable potential for asymmetric cyclopropanation and desymmetrizations of meso diols.
C. Mazet, V. Koehler, A. Pfaltz, Angew. Chem. Int. Ed., 2005, 44, 4888-4891.
A new nucleophilic isopropyl transfer reagent, triisopropylsulfoxonium tetrafluoroborate, converts after deprotonation with NaH a range of electron deficient alkenes, including several chalcone analogues, α,β-unsaturated ketones, dienones and quinones, plus α,β-unsaturated esters, nitrile, sulfone and nitro examples into the corresponding gem-dimethylcyclopropane compounds.
M. G. Edwards, R. J. Paxton, D. S. Pugh, A. C. Whitwood, R. J. K. Taylor, Synthesis, 2008, 3279-3288.
New and highly soluble iodonium ylides derived from malonate methyl ester show higher reactivity than common phenyliodonium ylides in the Rh-catalyzed cyclopropanation, C-H insertion, and transylidation reactions under homogeneous conditions.
C. Zhu, A. Yoshimura, L. Ji, Y. Wei, V. N. Nemykin, V. V. Zhdankin, Org. Lett., 2012, 14, 3170-3173.
Iodobenzene catalyzes an oxidative cyclization of Michael adducts of activated methylene compounds with nitroolefins or chalcones in the presence of mCPBA as terminal oxidant together with Bu4NI to provide a range of highly functionalized cyclopropanes with high diastereoselectivities.
Y. Li, H. Guo, R. Fan, Synthesis, 2020, 52, 928-932.
A Rh(III) catalyst promotes a cyclopropanation of electron deficient alkenes with N-Enoxyphthalimides via a directed activation of the olefinic C-H bond followed by two migratory insertions, first across the electron-deficient alkene and then by cyclization back onto the enol moiety. A newly designed isopropylcyclopentadienyl ligand drastically improves yield and diastereoselectivity.
T. Piou, T. Rovis, J. Am. Chem. Soc., 2014, 136, 11292-11295.
A cobalt(II) complex of a D2-symmetric chiral porphyrin is an effective catalyst for catalyzing asymmetric olefin cyclopropanation with α-cyanodiazoacetates. The reaction is suitable for both aromatic and aliphatic olefins, including electron-rich and poor olefins under mild conditions, affording the desired cyclopropane products in high yields with both high diastereo- and enantioselectivity.
S. Zhu, X. Xu, J. A. Perman, X. P. Zhang, J. Am. Chem. Soc., 2010, 132, 12796-12799.
[Co(P1)] is an effective catalyst for asymmetric cyclopropanation of various olefins with succinimidyl diazoacetate, providing the desired cyclopropane succinimidyl esters in high yields and excellent diastereo- and enantioselectivity. The cyclopropane succinimidyl esters serve for the synthesis of optically active cyclopropyl carboxamides.
J. V. Ruppel, T. J. Gauthier, N. L. Snyder, J. A. Perman, X. P. Zhang, Org. Lett., 2009, 11, 2273-2276.
In a Rh-catalyzed procedure for the cyclopropanation of alkenes with α-alkyl-α-diazoesters, sterically demanding carboxylate ligands serve to avoid β-hydride elimination. The use of triphenylacetate (TPA) as ligand also imparts high diastereoselectivity.
P. Panne, A. DeAngelis, J. M. Fox, Org. Lett., 2008, 10, 2987-2989.
A samarium-promoted cyclopropanation can be carried out on unmasked (E)- or (Z)-α,β-unsaturated carboxylic acids. In all cases the process is completely stereospecific and stereoselective. A mechanism has been proposed.
J. M. Concellón, H. Rodríguez-Solla, C. Simal, Org. Lett., 2007, 9, 2685-2688.
A diastereoselective Cu-catalyzed addition of diorganozinc reagents to readily available cyclopropene derivatives is directed by ester and oxazolidinone functions with excellent facial selectivity. The resulting cyclopropylzinc reagents can be captured via stereospecific reactions with electrophiles.
V. Tarwade, X. Liu, N. Yan, J. M. Fox, J. Am. Chem. Soc., 2009, 131, 5382-5383.
Efficient, simple, cheap, and environmentally benign preparations of cyclopropanes were achieved. One method is based on a 3-exo-trig cyclisation of various electron-deficient 2-iodoethyl-substituted olefins with zinc powder in a mixture of t-butyl alcohol and water, and the other on a 3-exo-tet cyclisation of various 1,3-dihalopropanes with zinc powder in ethanol.
D. Sakuma, H. Togo, Tetrahedron, 2005, 61, 10138-10145.
Cu-TolBINAP-catalyzed conjugate addition of alkyl Grignard reagents to 4-chloro-α,β-unsaturated esters, thioesters, and ketones leads to trans-1-alkyl-2-substituted cyclopropanes in good yield and high enantioselectivity. The versatility of this reaction is illustrated by the formation of key intermediates for the formal syntheses of cascarillic acid and grenadamide.
T. den Hartog, A. Rudolph, B. Maci, A. J. Minnaard, B. L. Feringa, J. Am. Chem. Soc., 2010, 132, 14349-14351.
Methyl 1-aryl-2-amino-cyclopropane carboxylates have been readily synthesized in high yields by Rh-catalyzed decomposition of aryldiazoacetates in the presence of N-vinylphthalimide. The reaction is highly trans-selective.
T. Melby, R. A. Hughes, T. Hansen, Synlett, 2007, 2277-2279.
A Rh-catalyzed enantio- and diastereoselective cyclopropanation of terminal and (Z)-internal 2-azadienes with donor/acceptor carbenes derived from α-diazoesters provides aminocyclopropanes with quaternary carbon stereogenic centers vicinal to the amino-substituted carbon. Transformations with internal azadienes afford cyclopropanes with three contiguous stereogenic centers.
X. Shao, S. J. Malcolmson, Org. Lett., 2019, 21, 7380-7385.
The first Corey-Chaykovsky epoxidation and cyclopropanation using trimethyl sulfonium iodide/trimethyl sulfoxonium iodide and KOH as base in the recyclable ionic liquid, (bmim)PF6 are described.
S. Chandrasekhar, Ch. Narasihmulu, V. Jagadeshwar, K. Venkatram Reddy, Tetrahedron Lett., 2003, 44, 3629-3630.
Dirhodium tetrakis-(R)-(1-(4-bromophenyl)-2,2-diphenylcyclopropanecarboxylate) (Rh2(R-BTPCP)4) is an effective chiral catalyst for enantioselective reactions of aryl- and styryldiazoacetates. Highly enantioselective cyclopropanations, tandem cyclopropanation/Cope rearrangements and a combined C-H functionalization/Cope rearrangement were achieved.
C. Qin, V. Boyarskikh, J. H. Hansen, K. I. Hardcastle, D. G. Musaev, H. M. L. Davies, J. Am. Chem. Soc., 2011, 133, 19198-19204.
(S)-(-)-indoline-2-yl-1H-tetrazole readily facilitates the enantioselective organocatalytic cyclopropanation of α,β-unsaturated aldehydes with sulfur ylides, providing cyclized product in excellent diastereoselectivities and enantioselectivities.
A. Hartikka, P. I. Arvidsson, J. Org. Chem., 2007, 72, 5874-5877.
Phenyliodonium ylides provide easy access to various 1,1-cyclopropane diesters using rhodium or copper catalysis and are safer and convenient alternatives to the corresponding diazo compounds. Moreover, the iodonium ylide of dimethyl malonate was obtained in 78% yield using improved conditions that involve a simple filtration step to isolate the desired product.
S. R. Goudreau, D. Marcoux, A. B. Charette, J. Org. Chem., 2009, 74, 470-473.
Three highly enantio- and diastereoselective one-pot procedures for the synthesis of cyclopropyl and iodocyclopropyl alcohols with up to four contiguous stereocenters are reported. Route 1 and 2 involve asymmetric addition of an alkylzinc reagent to an enal followed by diastereoselective cyclopropanation using either diiodomethane or iodoform to generate the zinc carbenoid, leading to cyclopropyl or iodocyclopropyl alcohols, respectively. Route 3 entails asymmetric vinylation of an aldehyde with divinylzinc reagents and subsequent diastereoselective cyclopropanation.
H. Y. Kim, A. E. Lurain, P. Garcia-Carcia, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2005, 127, 13138-13139.
Hydroboration of 1-alkynyl-1-boronate esters and in situ transmetalation furnishes 1-alkenyl-1,1-borozinc heterobimetallic intermediates. Reaction with aldehydes and in situ cyclopropanation generates B(pin) substituted cyclopropyl carbinols with excellent diastereoselectivities. Oxidation provides trisubstituted α-hydroxycyclopropyl carbinols, that allow access to both cis- and trans-2,3-disubstituted cyclobutanones via a facile pinacol-type rearrangement.
M. M. Hussain, H. Li, N. Hussain, M. Ureńa, P. J. Carroll, P. J. Walsh, J. Am. Chem. Soc., 2009, 131, 6516-6524.
An Ir-catalyzed enantioselective C(sp3)-H borylation of cyclopropanecarboxamides using a chiral bidentate boryl ligand provides β-borylated products with good to excellent enantioselectivities. The borylated products can be used as versatile precursors.
Y. Shi, Q. Gao, S. Xu, J. Am. Chem. Soc., 2019, 141, 10599-10604.
An organocatalytic asymmetric cascade Michael reaction of α,β-unsaturated aldehydes with bromomalonates, efficiently catalyzed by chiral diphenylprolinol TMS ether in the presence of base 2,6-lutidine, gives cyclopropanes in high enantio- and diastereoselectivities. Using NaOAc as base, a spontaneous ring-opening of cyclopropanes leads to (E) α-substituted malonate α,β-unsaturated aldehydes.
H. Xie, L. Zu, H. Li, J. Wang, W. Wang, J. Am. Chem. Soc., 2007, 129, 10886-10894.
Use of water as reaction medium for O-TMS-diarylprolinol-catalyzed cyclopropanation reactions of α,β-unsaturated aldehydes with diethyl bromomalonate enables a base-free reaction system. A modified O-TMS-diarylprolinol incorporating a hydrophobic alkyl side chain has been identified as a promising catalyst for this reaction.
U. Uria, J. L. Vicario, D. Badía, L. Carrillo, E. Reyes, A. Pesquera, Synthesis, 2010, 701-713.
An efficient solvent-controlled oxidative cyclization of Michael adducts of malonates with chalcones with the combination of iodosobenzene and tetrabutylammonium iodide enables the divergent synthesis of highly functionalized oxetanes and cyclopropanes in good yields with high diastereoselectivity.
Y. Ye, C. Zheng, R. Fan, Org. Lett., 2009, 11, 3156-3159.
trans-2-Aryl-3-nitro-cyclopropane-1,1-dicarboxylates undergo ring-opening rearrangement and the Nef reaction in the presence of BF3ˇOEt2 to give aroylmethylidene malonates. The products are potential precursors for heterocycles, such as imidazoles, quinoxalines, and benzo[1,4]thiazines.
T. Selvi, K. Srinivasan, J. Org. Chem., 2014, 79, 3653-3658.
The reaction of 1-aryl-2,2,2-trifluorodiazoethanes with alkenes provides trifluoromethyl-substituted cyclopropanes with high diastereoselectivity and enantioselectivity in the presence of an adamantylglycine-derived dirhodium complex Rh2(R-PTAD)4 as catalyst.
J. R. Denton, D. Sukumaran, H. M. L. Davies, Org. Lett., 2007, 9, 2625-2628.
A MW-based protocol enables a rapid preparation of 1,1-difluorocyclopropanes, using fluorinated acetate salts. The new procedure is not only considerably faster than conventional methods, but it also employs easily removed, low boiling-point solvents and avoids the use of highly toxic or ozone-depleting substances.
D. M. Gill, N. McLay, M. J. Waring, C. T. Wilkinson, J. B. Sweeney, Synlett, 2014, 25, 1756-1758.
Sodium bromodifluoroacetate (BrCF2CO2Na) is an effective difluorocarbene source for high-yielding synthesis of gem-difluorocyclopropanes and gem-difluorocyclopropenes under mild conditions.
K. Oshiro, Y. Morimoto, H. Amii, Synthesis, 2010, 2080-2084.
The application of continuous flow technology enabled a controlled generation of difluorocarbene from TMSCF3 and a catalytic quantity of NaI. The in situ generated electrophilic carbene reacts smoothly with a broad range of alkenes and alkynes to provide the corresponding difluorocyclopropanes and difluorocyclopropenes within 10 min residence time at high reaction concentrations.
P. Rulličre, P. Cyr, A. B. Charette, Org. Lett., 2016, 18, 1988-1991.
Nickel(0) catalysis enables the use of [1.1.1]propellane as a carbene precursor in cyclopropanations of a range of functionalized alkenes to give methylenespiro[2.3]hexane products. Computational studies provide support for initial formation of a Ni(0)-[1.1.1]propellane complex followed by concerted double C-C bond activation to give the key 3-methylenecyclobutylidene-nickel intermediate.
S. Yu, A. Noble, R. B. Bedford, V. K. Aggarwal, J. Am. Chem. Soc., 2019, 141, 20325-20334.
An efficient lithium amide-induced intramolecular cyclopropanation of bishomoallylic and trishomoallylic epoxides is described. The methodology is used in an asymmetric synthesis of sabina ketone.
D. M. Hodgson, Y. K. Chung, J.-M. Paris, J. Am. Chem. Soc., 2004, 126, 8654-8655.
Exposure of enynes containing a hydroxyl group at one of the propargylic positions to catalytic amounts of either PtCl2 or (PPh3)AuCl/AgSbF6 results in a selective rearrangement with formation of bicyclo[3.1.0]hexan-3-one derivatives. A total synthesis of the terpenes sabinone and sabinol is described.
V. Mamane, T. Gress, H. Krause, A. Fürstner, J. Am. Chem. Soc., 2004, 126, 8654-8655.
Halocycloalkenones are potent dienophiles in Diels-Alder cycloadditions. 2-Brominated cycloalkenone dienophiles are highly endo selective and significantly more reactive than their nonhalogenated parent compounds. A base-mediated reaction enables the facile conversion of brominated cyclobutanone Diels-Alder adducts to synthetically useful cyclopropyl derivatives.
A. G. Ross, S. D. Townsend, S. J. Danishefsky, J. Org. Chem., 2013, 78, 204-210.
The reaction of various 1,6-enynes with N2CHSiMe3 in the presence of RuCl(COD)Cp* as catalyst precursor leads to the general formation of alkenylbicyclo[3.1.0]hexanes at room temperature in good yield with high stereoselectivity. The catalytic formation of alkenylbicyclo[3.1.0]hexanes also takes place in the presence of N2CHCO2Et or N2CHPh.
F. Monnier, C. Vovard-Le Bray, D. Castillo, V. Aubert, S. Dérien, P. H. Dixneuf, L. Toupet, A. Ienco, C. Mealli, J. Am. Chem. Soc., 2007, 129, 6037-6049.
A new Pd-catalyzed oxidation reaction for the stereospecific conversion of enynes into cyclopropyl ketones proceeds with net inversion of geometry with respect to the starting olefin. This result is consistent with a mechanism in which the key cyclopropane-forming step involves nucleophilic attack of a tethered olefin onto the PdIV-C bond.
L. L. Welbes, T. W. Lyons, K. A. Cychosz, M. S. Sanford, J. Am. Chem. Soc., 2007, 129, 5836-5837.