Cycloaddition reactions cyclobutanes, synthesis

According to the Woodw ard-Hofmann rules the concerted thermal [2n + 2n] cycloaddition reaction of alkenes 1 in a suprafacial manner is symmetry-forbidden, and is observed in special cases only. In contrast the photochemical [2n + 2n cycloaddition is symmetry-allowed, and is a useful method for the synthesis of cyclobutane derivatives 2. 

An interesting reaction that has been developed over the past decade is the application of (2 + 2)-cycloaddition reactions to the synthesis of cyclophanes49. One of the earliest examples of this is the selective conversion of the bis(arylalkenes) 112 into the adducts 113. The yield of product is dependent to some extent on the chain length separating the aryl groups and the best yield of 41% is obtained when the separation includes four methylene units (n = 4). Lower yields are recorded with the other derivatives. Mixtures of products are formed when the m-isomers 114 are used. This affords 115 and 116. The yields of these are better than those obtained from the p-isomers 11250 51. Nishimura and coworkers52 have examined the ease with which such cyclobutanes, e.g. 115, n = 2,... 

Cyclobutanes, synthesis (Continued) by thermal cycloaddition reactions, 12, 1... 

Cycloaddition reactions, 162-165, 197-198 component analysis, 168 Diels-Alder, 162, 198 ethylene + ethylene, 198 orbital correlation diagram, 198 stereochemistry, 162-163 Cycloalkanols, synthesis, 277 Cyclobutadiene barrier, 91 ground state, 91 point group of, 5 self-reactivity, 97 SHMO, 151 structure, 309-310 Cyclobutane... 

Photochemical cyclobutane annealings are much more promising and find their way into synthesis to a greater extent. Photochemical cycloaddition reactions to enolized 1,3-diketones and consecutive ring openings via retroaldol reactions have been applied in ring expansion reactions numerous times. 

The photochemical [2 + 2] cycloaddition reaction of alkenes, the light-induced cycloaddition of two carbon-carbon ir-bonds to produce a cyclobutane, is a potentially highly useful reaction in organic synthesis since two new carbon-carbon bonds are formed and a maximum of four new stereocenters are introduced in the process. Ciamician reported the first example in 1908 when he observed the formation of carvone camphor (2) on prolonged exposure of carvone (1) to Italian sunlight (equation 1). ... 

Asymmetric [2 + 2] cycloaddition reaction affords a practical means of synthesis of optically active cyclobutanes, which can be used as useful intermediates in organic synthesis [138]. Narasaka reported that asymmetric [2 -i- 2] cycloaddition between acryloyl oxazolidinone derivatives and bis(methylthio)ethylene proceeded with high enantios-electivity when catalyzed by TADDOL-derived titanium complex (Sch. 58) [139]. The cyclobutane product was transformed into carbocyclic oxetanocin analogs or (-n)-grand-isol [140]... 

The [2 + 2] cycloaddition reaction is an excellent method for the synthesis of cyclophanes.691 For example, irradiation of the commercially available m-divinylbenzene (124) in dry benzene yields the cyclobutane 125, which then slowly photocyclizes to isomeric cyclophanes in a low chemical yield (<10% each) (Scheme 6.54).720... 

Some thermally forbidden [2 + 2]-cycloaddition reactions can be promoted by Lewis acids1-6. With chirally modified Lewis acids, the opportunity for application in asymmetric synthesis of chiral cyclobutanes arises (for a detailed description of these methods see Sections D.l. 6.1.3.. D.l. 61.4. and references 7, 28-30). Thus, a chiral titanium reagent, generated in situ from dichloro(diisopropoxy)titanium and a chiral diol 3, derived from tartaric acid, catalyzes the [2 + 2]-cycloaddition reaction of 2-oxazolidinone derivatives of a,/ -unsalurated acids 1 and the ketene thioacetal 2 in the presence of molecular sieves 4 A with up to 96 % yield and 98% ee. Fumaric acid substrates give higher yields and enantiomeric excesses than acrylic acid derivatives8. Michael additions are almost completely suppressed under these reaction... 

Both inter- and intramolecular [2-1-2] cycloaddition reactions have been used in synthesis. In intermolecular reactions, a common problem is that mixtures of regioisomers (sometimes referred to as head-to-tail and head-to-head products) in addition to more than one stereoisomer may be formed. In general, the head-to-tail regioisomer is the major product using an electron-rich alkene, whereas the head-to-head regioisomer is favoured using an electron-deficient alkene. For example, the first step in Corey s synthesis of caryophyllene involved addition of cyclohexenone to isobutene to give predominantly the trans-cyclobutane (head-to-tail) derivative 151 (3.107). 05... 

Variations on the theme of [2 + 2]cycloaddition reactions as a route to cyclobutanes continue to be developed. 1,2-Diynylcyclobutanes (29) can be prepared by triplet-sensitized photochemical dimerization of the corresponding enynes in general, this method cannot be used for the efficient synthesis of more highly substituted cyclobutanes. Similar photochemical methods have also been used to prepare a range of substituted ci5-l,2-diaminocyclobutanes (30), and the tricyclic compounds (31), which can serve as precursors to the tricyclo[4.2.0.0 ]octanes (32) via the Wolff rearrangement. ... 

Synthesis of a Polysubstituted Bicyclobutane - To broaden our collection ot bicyclobutane monomers, we have e qplored the utility of zwitterionic cycloaddition reactions to synthesize the required cyclobutane precursors. Such reactions of electron-rich olefins with electron-poor olefins were studied by Brannock and coworkers (19). To obtain substituents at the proper locations on the cyclobutane ring, we used trisubstituted electrophilic olefins (20) in the following reaction sequence ... 

The [2 + 2] cycloaddition reaction continues to dominate the synthesis of cyclobutanes, and a timely review on the intramolecular [2 -t- 2] photoaddition-cyclobutane fragmentation sequence has appeared. The first stable crystalline /rarts-fused cyclobutanone has been reported to be the ketone (16), which does not readily epimerize to the cis-fused isomer. The product is formed by photolysis of the enone (14) and the ketene acetal (15) followed by mild hydrolysis. ... 

G. Simonneaux et al. (57) published the synthesis and complexation to ruthenium(II) and iron(in) m 5(9-tetraphenylporphyrins of two new fluorinated alkyl isocyanides, 2-monofluoroethyl isocyanide and 2,2,2-trifluoroethyl isocyanide. A new synthesis of trifluoromethyl isocyanide, pentafluoroethyl isocyanide and heptafluoropropyl isocyanide from R-N=Cp2 (R = CF3, C2F5, C3F7) using triphenyl phosphine has been reported (58). Geometries and HOMO and LUMO energies of fluorinated vinyl isocyanides have been calculated (59). Pentacarbonyl chromium complexes of both isomers of the first fluorinated diisocyanide, l,2-diisocyano-l,2,3,3,4,4-hexafluoro cyclobutane have been isolated from a [2+2] cycloaddition reaction of pentacarbonyl(trifluorovinyl isocyanide) chromium. The structure of the cis isomer has been elucidated by X-ray crystallography (60),... 

Many [2+2] cycloaddition reactions are synthetically important as they provide rapid and efficient synthesis of strained cyclobutane rings and their derivatives. The reactions are typically performed imder thermal or photochemical activation or with the Lewis acids. However, there are some reports of the application of microwave irradiation to perform [2+2] cycloaddition reactions. 

The intramolecular photochemical synthesis of phanes can be apphed to the construction of covalent templates. Moreover, the cyclobutane ring(s) formed by the cycloaddition reaction can act as a stereochemical control forcing the phane conformation to one side similar to a caUper system. Other work has been directed towards the synthesis of receptors and ionophores apphcable to host-guest chemistry. ... 

Cyclo ddltion. Ketenes are ideal components ia [2 + 2] cycloadditions for additions to the opposite sides of a TT-system as shown ia the cyclobutane product (2) ia Figure 1. Electron-rich double bonds react readily with ketenes, even at room temperature and without catalysts. In conjugated systems, ketenes add ia a [2 + 2] fashion. This is illustrated ia the reaction foUowiag, where the preferential orientation of L (large substituent) and S (small substituent) is seen (40). This reaction has been used ia the synthesis of tropolone [533-75-5]. 

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