Cyclobutanation intramolecular

As final examples, the intramolecular cyclopropane formation from cycloolefins with diazo groups (S.D. Burke, 1979), intramolecular cyclobutane formation by photochemical cycloaddition (p. 78, 297f., section 4.9), and intramolecular Diels-Alder reactions (p. 153f, 335ff.) are mentioned. The application of these three cycloaddition reactions has led to an enormous variety of exotic polycycles (E.J. Corey, 1967A). 

It has also been proposed that the ring-opened radicals may undergo ring-closure to a cyclobutane (Scheme 4.23).202,2 8 At this stage the only evidence for this pathway is observation of signals in the NMR spectrum of the polymer that cannot be rationalized in terms of the other structures. There is no precedent for 1,4-ring-closure of a 3-butenyl radical in small molecule chemistry and the result is contrary to expectation based on stcrcoclcctronic requirements for intramolecular addition (Section 2.3.4). However, an alternate explanation has yet to be proposed. The possibility of carbonium ion intermediates should not be discounted. 

Dihydropyran-4-ones are a source of phenols via an intramolecular [2+2] photocycloaddition reaction and a Lewis-acid catalysed cleavage of the cyclobutane moiety <96TL1663>. 

In the crystal of 1,4-dicinnamoylbenzene (1,4-DCB) (see Fig. 12), the distances between the intermolecular photoadductive carbons are 3.973 and 4.086 A for one cyclobutane ring, and 3.903 and 3.955 A for the other. The two topochemical pathways may occur competitively in a single crystal of 1,4-DCB at the initial stage of reaction. Then, both intramolecular photodimerization and intermolecular photopolymerization of the diolefinic mono-cyclobutane intermediate occur competitively to give tricyclic dimer 21,22,23,24-tetraphenyl-l,4,ll,14-tetraoxo-2(13),12(13-diethanol, [4.4] para-cyclophane or oligomers (Hasegawa et al., (1985). On photoirridation at room temperature the 1,4-DCB crystal gives >90% of the tricylic... 

Intramolecular [2 + 2] photocycloadditions of alkenes is an important method of formation of compounds containing four-membered rings.184 Direct irradiation of simple nonconjugated dienes leads to cyclobutanes.185 Strain makes the reaction unfavorable for 1,4-dienes but when the alkene units are separated by at least two carbon atoms cycloaddition becomes possible. 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

Mechanistic evidence indicates 450,451> that the triplet enone first approaches the olefinic partner to form an exciplex. The next step consists in the formation of one of the new C—C bonds to give a 1,4-diradical, which is now the immediate precursor of the cyclobutane. Both exciplex and 1,4-diradical can decay resp. disproportionate to afford ground state enone and alkene. Eventually oxetane formation, i.e. addition of the carbonyl group of the enone to an olefin is also observed452. Although at first view the photocycloaddition of an enone to an alkene would be expected to afford a variety of structurally related products, the knowledge of the influence of substituents on the stereochemical outcome of the reaction allows the selective synthesis of the desired annelation product in inter-molecular reactions 453,454a b). As for intramolecular reactions, the substituent effects are made up by structural limitations 449). 

The same type of bis-functionalization has been reported for the palladium-catalyzed borylstannylative carbocy-cyclization of 1,6-, 1,5-, 1,7-diynes, bis-propargylamine, and ether.377 It should be noted that even 1,2-dialkylidene cyclobutane can be obtained in reasonable yield. Ito has proposed the related silaborative reaction involving nickel(O) catalysis.378 This reaction has been performed in an intra- and intermolecular fashion. The intramolecular reaction allows the formation of cyclic dienes and the intermolecular process proceeds through a dimerization of alkynes to give acyclic dienes. 

The chemistry of cyclobutanes was remarkably exploited by Oppolzer42, who reported that the aldol condensation of the acetal (122) with l,2-Ws(trimethylsiloxy)-cyclobutene was catalyzed by BF3 Et20 to afford the eyclobutanone (123), which was refluxed with pTsOH in benzene to give 1,3-cyclopentanedione (124). On treatment with acetylchloride in pyridine at 0 °C, the compound (124) was transformed to the enol acetate (125) Irradiation of (125) gave the intramolecular photoadduct (126). Then on successive treatments with MeMgl, KOH and MsCl in... 

Intramolecular (2 + 2)-photocycloaddition has proved to be an excellent route to the synthesis of the so-called cage compounds. Ideally, this route utilizes substrates where the two alkene moieties are held face-to-face within a pre-formed structure. The irradiation brings about excitation and coupling of the two groups to afford a cyclobutane ring. 

ET-induced cycloadditions of polycyclic olefins and cycloreversions of cyclobutane species have been studied by ESR spectroscopy [266]. Upon chemical and electrochemical reduction, 2,2 -distyrylbiphenyl rearranges by intramolecular coupling into a bis-benzylic dihydrophenanthrene dianion (Scheme 1), which can be either protonated to a 9,10 -dibenzyl-9,10-dihydrophenanthrene or oxidatively coupled to a cyclobutane species. It is interesting to note that the intramolecular bond... 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

The sodium cation chelation by the bis(enone) anion-radicals shown in Scheme 3.52 controls their further transformations although they proceed at the expense of other reaction centers (Yang et al. 2004). This kind of intramolecular cyclobutanation is characterized with the pronounced cis-stereoselectivity. However, this stereoselectivity disappears if the reaction proceeds in the presence of the tetrabutylammonium cation, when such a chelation is impossible. 

Detailed mechanistic information concerning an intramolecular arylalkene cycloaddition yielding cyclobutane derivatives via a radical cation process gener-... 

Both target compounds discussed in this review, kelsoene (1) and preussin (2), provide a fascinating playground for synthetic organic chemists. The construction of the cyclobutane in kelsoene limits the number of methods and invites the application of photochemical reactions as key steps. Indeed, three out of five completed syntheses are based on an intermolecular enone [2+2]-photocycloaddition and one—our own—is based on an intramolecular Cu-catalyzed [2+2]-photocycloaddition. A unique approach is based on a homo-Favorskii rearrangement as the key step. Contrary to that, the pyrrolidine core of preussin offers a plentitude of synthetic alternatives which is reflected by the large number of syntheses completed to date. The photochemical pathway to preussin has remained unique as it is the only route which does not retrosynthetically disconnect the five-membered heterocycle. The photochemical key step is employed for a stereo- and regioselective carbo-hydroxylation of a dihydropyrrole precursor. 

The first total synthesis of a racemic dolastane (rac-llO) was apparently published by Pattenden as a short communication 1986 followed in 1988 by a full paper [77, 78]. Pattenden s strategy is based on an intramolecular [2+2]-photocycloaddition/cyclobutane fragmentation to transform the diene 133 into the hydroazulene 136 (Scheme 20). In between the cycloaddition... 

Diels-Alder, imino dienophiles, 65, 2 Diels-Alder, intramolecular, 32, 1 Diels-Alder, maleic anhydride, 4, 1 [4 -h 3], 51, 3 of enones, 44, 2 of ketenes, 45, 2 of nitrones and alkenes, 36, 1 Pauson-Khand, 40, 1 photochemical, 44, 2 retro-Diels-Alder reaction, 52, 1 53, 2 [6-h4], 49, 2 [3-h2], 61, 1 Cyclobutanes, synthesis ... 

Cyclic diones or silylmethyl-protected diones react with olefines in a [2+2] fashion. Addition of these compounds to Cjq [341] leads initially to the cyclobutane fused fullerenes, which are not stable and are readily oxidized and rearranged to the furanylfullerenes 300 and 301 (Scheme 4.56). The intermediate 299 probably reacts by either intermolecular oxidation with 2 to yield 300 or by an intramolecular oxidation with the triplet fullerene moiety to yield 301. 

Intramolecular bond formations include (net) [2 + 2] cycloadditions for example, diolefin 52, containing two double bonds in close proximity, forms the cage structure 53. This intramolecular bond formation is a notable reversal of the more general cycloreversion of cyclobutane type olefin dimers (e.g., 15 + to 16 +). The cycloaddition occurs only in polar solvents and has a quantum yield greater than unity. In analogy to several cycloreversions these results were interpreted in terms of a free radical cation chain mechanism. 

Table 12. Cyclobutanes by Intramolecular Nucleophilic Substitution of Cyclohexanone Derivatives...

The exhaustive controlled-potential reduction of 6-chioro-l-phenylhex-l-yne at — 1.57 V in dimethylformamide containing tetrabutylammonium perchlorate gave a mixture of products. among which was ( >(2-phcnylvinyl)cyclobutane (9).11 It is probable that the mechanism involves initial isomerization of the acetylene to an allene 8 which is reduced at — 1.57 V to the radical anion. Protonation and further onc-clectron reduction then yield the allylic anion. An intramolecular nucleophilic substitution eventually gives the cyclobutane.11... 

Bisacryloylimides 7 undergo thermal intramolecular cycloadditions giving either head-to-head or head-to-tail cyclobutanes 8 or 9, respectively, depending on the substituent at the double... 

Ethyl aluminum dichloride can catalyze the intramolecular cycloaddition of dienones 1 giving polycyclic cyclobutanes 2 in good yields.21 The effect of temperature and catalyst is important in determining the extent of [2 + 2] cycloadducts and ene-type products formed. 

A special case of the preparation of cyclobutanes from 1,5-dienes via valence isomerization is the use of acyclic or cyclic 1,5,7-trienes which give four-membered rings via an intramolecular [7t + 7ts2] cycloaddition (Diels-Alder reaction). This variant is illustrated for monocyclic tricnes 18 and 20 where two 71-bonds are transformed into a-bonds, resulting in tricyclic compounds 1968 and 21.09... 

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