Methylenecyclobutane

• CAT Number: M047814
• CAS Number: 1120-56-5
• Molecular Formula: C5H8
• Molecular Weight: 68.119
• Purity: ≥95%
• Storage: -20°C
• IUPAC Name: methylidenecyclobutane
• InChI: InChI=1S/C5H8/c1-5-3-2-4-5/h1-4H2
• InChIKey: QIRVGKYPAOQVNP-UHFFFAOYSA-N
• SMILES: C=C1CCC1

Methylcyclopropane(CAS: 1120-56-5) is an organic compound with the structural formula C3H5CH3. This colorless gas is the monomethyl derivative of cyclopropane. Methylcyclopropane, like many other cyclopropanes, undergoes ring-opening reactions. Bond cleavage in certain reactions is also reported in conjunction with the use of methylenecyclopropane groups as protective groups for amines.

Reference

[1]. Org Lett. 2019 Mar 1;21(5):1506-1510. doi: 10.1021/acs.orglett.9b00309. Epub 2019 Feb 21.
Stereoselective Construction of Methylenecyclobutane-Fused Indolines through Photosensitized [2+2] Cycloaddition of Allene-Tethered Indole Derivatives.
Arai N(1), Ohkuma T(1)(2).
Author information: (1)Division of Applied Chemistry, Faculty of Engineering , Hokkaido University , Sapporo , Hokkaido 060-8628 , Japan. (2)Frontier Chemistry Center, Faculty of Engineering , Hokkaido University , Sapporo , Hokkaido 060-8628 , Japan.
Erratum in Org Lett. 2019 Oct 18;21(20):8507.
Irradiation of 1-(hexa-4,5-dienoyl)indole derivatives in the presence of an aromatic ketone by a high-pressure mercury lamp through Pyrex glass gave the corresponding cyclized products stereoselectively in high yields. The major part of the products was an all- cis-fused methylenecyclobutane-type compound produced through [2+2] cycloaddition, accompanied by small amounts of alkynes via 1,5-hydrogen transfer of a biradical intermediate. Among a range of aromatic ketones, 3',4'-dimethoxyacetophenone was found to sensitize the substrate quite effectively.
DOI: 10.1021/acs.orglett.9b00309 PMID: 30789275

[2]. Antivir Chem Chemother. 2002 Jul;13(4):251-62. doi: 10.1177/095632020201300406.
Synthesis of methylenecyclobutane analogues of nucleosides with axial chirality and their phosphoralaninates: a new pronucleotide effective against Epstein-Barr virus.
Wang R(1), Kern ER, Zemlicka J.
Author information: (1)Department of Chemistry, Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Mich, USA.
Methylenecyclobutane analogues of 2'-deoxyadenosine, 2'-deoxyguanosine and 2'-deoxycytidine, and the corresponding phosphoralaninate pronucleotides comprising adenine and guanine bases, were synthesized as potential antiviral agents. Phosphoralaninate of adenine methylenecyclobutane was a potent inhibitor of replication of Epstein-Barr virus (EBV) in Daudi cell culture. Phosphoralaninate of guanine analogue was inactive but both pronucleotides were substrates for porcine liver esterase. Adenine methylenecyclobutane analogue was deaminated by adenosine deaminase.
DOI: 10.1177/095632020201300406 PMID: 12495213 [Indexed for MEDLINE]

[3]. J Org Chem. 2021 Mar 19;86(6):4714-4732. doi: 10.1021/acs.joc.1c00104. Epub 2021 Mar 5.
Copper-Catalyzed Tandem Cross-Coupling/Thermally Promoted [2 + 2] Cycloaddition of 1,6-Enynes and Diazo Compounds To Assemble Methylenecyclobutane-Fused Ring System.
Chen N(1), Zhou T(1), Zhang H(1), Zhu Y(1), Lang M(1), Wang J(1)(2), Peng S(1).
Author information: (1)School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, People's Republic of China. (2)School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, People's Republic of China.
An unprecedented copper-catalyzed tandem reaction of 1,6-enynes with diazo compounds via a cross-coupling/[2 + 2] cycloaddition sequence was reported. A library of methylenecyclobutane-fused ring systems including cyclobuta[b]indolines, cyclobuta[b]benzofuran, benzo[b]cyclobuta[d]thiophene, and bicyclo[3.2.0] structures were obtained in moderate to excellent yields under very mild reaction conditions. The reaction exhibited high proximal-regioselectivity and diastereoselectivity. Moreover, 1,6-allenene has proven to be the key intermediate and proceeds via a thermally promoted [2 + 2] cycloaddition in the absence of copper catalyst.
DOI: 10.1021/acs.joc.1c00104 PMID: 33667091

[4]. Org Lett. 2019 Oct 18;21(20):8507. doi: 10.1021/acs.orglett.9b03407. Epub 2019 Oct 7.
Correction to "Stereoselective Construction of Methylenecyclobutane-Fused Indolines through Photosensitized [2+2] Cycloaddition of Allene-Tethered Indole Derivatives".
Arai N, Ohkuma T.
Erratum for Org Lett. 2019 Mar 1;21(5):1506-1510.
DOI: 10.1021/acs.orglett.9b03407 PMID: 31589454

[5]. Org Lett. 2007 Mar 29;9(7):1303-6. doi: 10.1021/ol070178r. Epub 2007 Mar 10.
PhI(OAc)2 -mediated novel 1,3-dipolar cycloaddition of methylenecyclopropanes (MCPs), vinylidenecyclopropanes (VCPs), and methylenecyclobutane (MCB) with phthalhydrazide.
Liu LP(1), Lu JM, Shi M.
Author information: (1)State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, China.
[structure: see text]. Iodobenzene diacetate-mediated reactions of methylenecyclopropanes 1, vinylidenecyclopropanes 2, and a methylenecyclobutane 3a with phthalhydrazide give the corresponding [3+2] cycloaddition products in good yields under mild conditions. In these reactions, phthalhydrazide was transformed to a 1,3-dipole intermediate in the presence of iodobenzene diacetate. A plausible reaction mechanism has been proposed.
DOI: 10.1021/ol070178r PMID: 17348667