Synthesis of cyclobutanes
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.
A copper hydride-catalyzed, enantioselective, intramolecular hydroalkylation of halide-tethered styrenes enables the synthesis of enantioenriched cyclobutanes, cyclopentanes, indanes, and six-membered N- and O-heterocycles.
Y.-M. Wang, N. C. Bruno, A. L. Placeres, S. Zhu, S. L. Buchwald, J. Am. Chem. Soc., 2015, 137, 10524-10527.
(E)- and (Z)-silyl and aryl-subsituted homoallylic methanesulfonates were converted to the corresponding cis- and trans-1-silyl-2-borylcyclobutanes as well as 1-phenyl-2-borylcyclobutanes in the presence of a CuCl/dppp catalyst, bis(pinacolato)diboron, and K(O-t-Bu)in THF. Stereospecific derivatizations of the cis- and trans-borylcyclobutanes were carried out to demonstrate the utility of the borylcyclobutanes.
H. Ito, T. Toyoda, M. Sawamura, J. Am. Chem. Soc., 2010, 132, 5990-5992.
Highly strained bicyclo[1.1.0]butyl boronate complexes, which were prepared by reacting boronic esters with bicyclo[1.1.0]butyl lithium, react with a wide range of electrophiles to form a diverse set of 1,1,3-trisubstituted cyclobutanes with high diastereoselectivity via difunctionalization of the strained central C-C σ-bond of the bicyclo[1.1.0]butyl unit.
S. H. Bennett, A. Fawcett, E. H. Denton, T. Biberger, V. Fasano, N. Winter, V. K. Aggarwal, J. Am. Chem. Soc., 2020, 142, 16766-16775.
Palladium-catalyzed cross-coupling reactions of cyclobutanone-derived N-sulfonylhydrazones with aryl or benzyl halides provide structurally diversified products including cyclobutenes, methylenecyclobutanes, and conjugated dienes in very good yields. The reaction also offers a promising route for the synthesis of enantioenriched four-membered-ring molecules.
X. Ning, Y. Chen, F. Hu, Y. Xia, Org. Lett., 2021, 23, 8348-8352.
A [2 + 2] cycloaddition of terminal alkenes with allenoates enables a rapid synthesis of 1,3-substituted cyclobutanes in high yield under simple and robust reaction conditions.
M. L. Conner, M. K. Brown, J. Org. Chem., 2016, 81, 8050-8060.
A diverse range of unsymmetrical tri- and tetrasubstituted cyclobutane structures can be produced in good yields and excellent diastereoselectivities using an efficient [2+2] heterodimerization of dissimilar acyclic enones upon visible light irradiation in the presence of a ruthenium(II) photocatalyst. The reaction is promoted by any visible light source.
J. Du, T. P. Yoon, J. Am. Chem. Soc., 2009, 131, 14604-14606.
N,O-Acetals derived from α,β-unsaturated β-aryl substituted aldehydes and (1-aminocyclohexyl)methanol undergo a catalytic enantioselective [2 + 2] cycloaddition to a variety of olefins under visible light irradiation (λ = 459 nm). The photocycloaddition is catalyzed by a chiral phosphoric acid with thioxanthone moieties for a facile triplet energy transfer.
F. Pecho, Y. Sempere, J. Gramüller, F. M. Hörmann, R. M. Gschwind, T. Bach, J. Am. Chem. Soc., 2021, 143, 9350-9354.
Propellanes have tremendous potential to be exploited in synthetic organic chemistry. An experimentally simple procedure provides cyclobutane-containing allenes and alkynes through a copper-catalyzed ring opening of [1.1.1]propellane and subsequent reaction with alkynes.
D. Lasányi, G. L. Tolnai, Org. Lett., 2019, 21, 10057-10062.
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.
Ru(bipy)3Cl2 is a visible light photocatalyst for [2+2] enone cycloadditions. Various aryl enones participate readily in the formation of the cyclobutane products, and the diastereoselectivity is excellent. A mechanism is proposed in which a photogenerated Ru(bipy)3+ complex promotes one-electron reduction of the enone substrate, which undergoes subsequent radical anion cycloaddition.
M. A. Ischay, M. E. Anzovino, J. Du, T. P. Yoon, J. Am. Chem. Soc., 2008, 130, 12886-12887.
Angle strain in methylene cyclobutane drives a cross-enyne metathesis with 1-alkynes, giving 1,1,3-trisubstituted 1,3-dienes in good isolated yields. An extensive survey of Grubbs’ second-generation catalysts led to optimized reaction conditions.
D. A. Clark, B. S. Basile, W. S. Karnofel, S. T. Diver, Org. Lett., 2008, 10, 4927-4929.
Bicyclo[2.1.1]hexanes have become increasingly popular building blocks in medicinal chemistry as bridged scaffolds that provide unexplored chemical space. An intramolecular crossed [2 + 2] photocycloaddition of styrene derivatives provides bicyclo[2.1.1]hexanes in excellent yields enabled by triplet energy transfer.
T. Rigotti, T. Bach, Org. Lett., 2022, 24, 8821-8825.