New short step general synthesis of isobenzofuran-1(3H)-ones (phthalides) based on a single or double β-scission of alkoxyl radicals generated from 1-ethyl-benzocyclobuten-1-ols and from 1,3-dihydroisobenzofuran-1-ols; synthesis of some natural phthalides
“…Kobayashi et al synthesized 3-alkylphthalides 650 by the β-scisson of alkoxyl radicals generated by the photolysis of the hypoiodites 649 , which, in turn, was produced by the irradiation of catacondensed benzocyclobuten-1-ol 648 in benzene containing mercuric oxide (HgO) and iodine at room temperature (Scheme ) . The yield of the reaction depends upon the size of the nonaromatic ring and substitutions in the benzene ring.…”
Section: Phthalidesmentioning
confidence: 99%
“…199b A DCC-mediated coupling of 613 with arylpropiolic acid 614 gave enyne 615, which on heating produced dihydrobenzimidazole 616 in 84% yield. Oxidation of 207 The yield of the reaction depends upon the size of the nonaromatic ring and substitutions in the benzene ring. Increase in the ring size of nonaromatic ring, that is, cyclohexane to cycloheptane, decreases the yields.…”
Scheme 10. Schmalz Synthesis of 3-Substituted Phthalides from 2-Formylketones Scheme 11. Enantioselective Synthesis of Phthalides via Ketone Hydroacylation Scheme 12. Synthesis of 3-Alkylphthalides from Sulfonylmethyl Benzoic Acids Scheme 13. Synthesis of an Isobenzofuranone via Thermolysis of a Bromomethylbenzoate Scheme 14. Kraus Approach to 3-Cyanophthalide Scheme 15. Ohzeki and Mori Synthesis of (−)-3-Butyl-7hydroxyphthalide Scheme 16. Asymmetric Dihydroxylation-Lactonization Route to Phthalides Chemical Reviews Review dx.
“…Kobayashi et al synthesized 3-alkylphthalides 650 by the β-scisson of alkoxyl radicals generated by the photolysis of the hypoiodites 649 , which, in turn, was produced by the irradiation of catacondensed benzocyclobuten-1-ol 648 in benzene containing mercuric oxide (HgO) and iodine at room temperature (Scheme ) . The yield of the reaction depends upon the size of the nonaromatic ring and substitutions in the benzene ring.…”
Section: Phthalidesmentioning
confidence: 99%
“…199b A DCC-mediated coupling of 613 with arylpropiolic acid 614 gave enyne 615, which on heating produced dihydrobenzimidazole 616 in 84% yield. Oxidation of 207 The yield of the reaction depends upon the size of the nonaromatic ring and substitutions in the benzene ring. Increase in the ring size of nonaromatic ring, that is, cyclohexane to cycloheptane, decreases the yields.…”
Scheme 10. Schmalz Synthesis of 3-Substituted Phthalides from 2-Formylketones Scheme 11. Enantioselective Synthesis of Phthalides via Ketone Hydroacylation Scheme 12. Synthesis of 3-Alkylphthalides from Sulfonylmethyl Benzoic Acids Scheme 13. Synthesis of an Isobenzofuranone via Thermolysis of a Bromomethylbenzoate Scheme 14. Kraus Approach to 3-Cyanophthalide Scheme 15. Ohzeki and Mori Synthesis of (−)-3-Butyl-7hydroxyphthalide Scheme 16. Asymmetric Dihydroxylation-Lactonization Route to Phthalides Chemical Reviews Review dx.
“…Kobayashi et al have reported a useful method for the synthesis of the phthalides 488 from cyclobutarene derivative 486 . Their procedure involves regioselective β-scission of the alkoxy radical 487b generated by photolysis of the hypoiodite 487a (Scheme ). , 111 …”
Section: E Oxidation and Reduction Reactionsmentioning
A general method for the synthesis of cyclobutarenes involves 1,4-elimination from adjacent benzylic positions, followed by ring closure of the resulting o-quinodimethane. The earliest report in which an o-quinodimethane was implicated was the reaction of R,R,R′,R′-tetrabromo-o-xylene (4) with iodide to give the 1,2-dibromocyclobutarene 6, via o-quinodimethane 5. Treatment of 6 with NaI in acetone gave diiodide 7, which on catalytic reduction gave 1 (Scheme 1). [15][16][17] Cava and co-workers confirmed that 5 was an intermediate by trapping experiments using sev-eral dienophiles. 18 A similar procedure has been used to prepare 1,2-diphenylcyclobutarene. 19 Heterocyclic analogues may also be prepared by the 1,4-elimination of halogen from suitable precursors. Compounds 9 and 11 have been synthesized from 8 and 10, respectively, as illustrated in Scheme 2. 20 A variation of the method involves the conversion of R-alkyl-R-bromosulfones into cyclobutarenes using tetrabutylammonium fluoride (TBAF) in acetonitrile at 20-25 °C to effect the elimination. 21 The desired cyclobutarene is often accompanied by olefinic side products, as illustrated in the preparation of cyclobutarene 13, which is accompanied by 14 (eq 1) (Table 1). Anil K. Sadana was born in Panipat, India. He did his M.Sc (1990) and M. Phil (1992) from Kurukshetra University, India. He obtained his Ph.D. degree in 1999 under the guidance of Prof. Om Prakash. His Ph.D. work focused on the utility of hypervalentiodine reagents in the synthesis of heterocyclic compounds. He then joined Prof. W. E. Billups lab as postdoctoral research associate in 2000. He is presently working on small ring compounds and carbon nanotubes. Rajesh Kumar Saini was born in 1966 in Ambala, India. He received his masters degree in 1989 and his Ph.D. in 1996 from Kurukshetra University, India. After his doctorate he moved to the United States for his postdoctoral studies. After a brief stay at Sam Houston State University he joined Rice University, where he is working as a Research Scientist in the laboratories of Prof. W. E. Billups and Prof. Richard E. Smalley. His research has concentrated on small ring compound and the development of carbon nanotube chemistry. W. E. Billups was born in 1939 in Huntington, West Virginia. He received his B.S. in Chemistry Degree from Marshall University in 1961. This was followed by a period in industry after which he entered the graduate school of the Pennsylvania State University in 1968 and received the Ph.D. in 1970. He then joined the chemistry department at Rice University. He served as the Department Chair from July 1985 until December 1991. His research interests are divided among the areas of small-ring compounds, reactive intermediates, chemistry of free metal atoms and more recently fullerene and carbon nanotube chemistry.
“…1). Also notable is the great deal of effort devoted by these authors to the study of the /?-fragmentation of cyclobutanoxyl and cyclobutenoxyl radicals and their application to the synthesis of, among others, phthalides, [27] phthalide lignans [28] and (*)-himachalene [29]. In general, two-carbon ring expansion reactions are observed as indicated (Eq.…”
The /?-fragmentation reaction is the reversible homolytic cleavage of a C-C bond a,P to an alkoxyl radical (I) which gives rise to a carbon radical and a C-0 double bond (11) (Scheme 1) [ 11. The equilibrium is strongly displaced to the fragmented Cradical (11). This is especially more pronounced in cyclopentane or smaller ring systems, or in a-substituted systems (R = alkyl, allyl, aryl) where the radical could be stabilized. For the cyclopentyloxyl radical, the equilibrium constant k,-/k, is approximately 2000, while it is only 10 for the cyclohexanyloxyl radical [2]. The formation of the final products 111 and IV is strongly influenced not only by the equilibrium constant but also by kl and k2, and the reaction can be best interpreted by using the Curtin-Hammett kinetic principle (31. In some cases when the reagent used reacts much faster with alkoxyl radicals than with carbon radicals (kl >> kz), the reverse cyclization reaction is possible and alkyl radicals can add intramolecularly to aldehydes or ketones generating alkoxyl radicals despite the unfavorable equilibrium [4].The regioselectivity of the fragmentation is not always apparent. In most cases the more stable radical is formed, but the different constants of equilibrium must be taken into account. A study of the fragmentation of 9-decalinoxyl radicals realized by Beckwith et al. is a good example of this [5]. Rearrangement at 0°C of 9-decalinyl hypobromite gives 6-bromocyclodecanone, whereas 2-(4-bromobutyl)-cyclohexanone is obtained at 8 1 "C. The increase in temperature displaces the equilibrium to the formation of an a priori less stable primary radical. The effect of alkyl substituents and ring size on the regioselectivity of the alkoxyl radical fragmentation has recently been evaluated by computational methods [6]. The importance of the activation energy and the energy of the reaction has been examined for a variety of cyclic and acyclic alkoxyl radicals.
Radicals in Organic Synthesis Edited
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