Allenes, cyclization reaction

That the thermal isomerizations of these substrates lie completely on the side of the cyclic structures 324 comes as no surprise after what has been said about the energetics of the allene cyclization reactions above [125] the cydoisomerization may also be induced by metal salts, such as cuprous chloride, incidentally [136]. 

Gange, D. Magnus, P. An unusual new allene cyclization reaction. Synthesis of dihydro-furan-3(2H)-ones. J. Am. Chem. Soc. 1978, 100, 7746-7747. 

Crystal-to-Crystal Cyclization Reactions of Allene Derivatives... 

A wide variety of five-membered zirconacydes 8 may be formed by the formal co-cycliza-tion of two 7i-components (3 and 6 alkene, alkyne, allene, imine, carbonyl, nitrile) on zir-conocene ( Cp2Zr ) (Scheme 3.2) [2,3,8]. The co-cydization takes place via the r 2-complex 5 of one of the components, which is usually formed by complexation of 3 with a zircono-cene equivalent (path a) ( Cp2Zr itself is probably too unstable to be a true intermediate) or by oxidation on the metal (cyclometallation/p-hydrogen elimination) (path b). Two additional routes to zirconocene r 2-complexes are by the reverse of the co-cyclization reaction (i. e. 8 reverting to 5 or 9 via 7), and by rearrangement of iminoacyl complexes (see Section... 

The structural variety increases if the second (and further) substituent(s) is (are) not bound to the allene nucleus. For vinylallene (2), the additional vinyl group can be introduced at C-5, leading to 1,2,4,6-heptatetraene (22 only. E-isomer shown) or at C-4, providing 4-methylene-l,2,5-hexatriene (23), the former being an important substrate for cyclization reactions, as will be discussed in Section 5.5 (Scheme 5.2). 

Reaction with a first aldehyde transforms 176 into the vinylphosphonium chloride 177, which for practical reasons is subjected to an anion-exchange process, leading to the phosphonium salt 178. From this, phenyllithium treatment liberates the allenic phosphorane 179, an intermediate that has previously been used to prepare allenes from aldehydes [69], in the present case providing the products 180. The same protocol has also been applied to o-alkynylbenzaldehydes to yield allenes of interest as model compounds for the study of Schmittel and Myers-type cyclization reactions [70]. 

In later studies by various groups, the enyneallene motif was incorporated into more complex hydrocarbon structures, allowing not only a better understanding of the Myers cyclization but also the generation of polycyclic hydrocarbons, some of them resembling the steroid core unit. Conceptually, these latter cyclizations are reminiscent of Johnson s biomimetic cyclization reactions with the main difference that here radical intermediates are involved rather than carbocations. Typical starting materials in these studies are the allenes 221 [87], 222 [88] and 223 [89], their cyclization behavior being discussed in Chapter 20. 

Cycloadditions and cyclization reactions are among the most important synthetic applications of donor-substituted allenes, since they result in the formation of a variety of carbocyclic and heterocyclic compounds. Early investigations of Diels-Alder reactions with alkoxyallenes demonstrated that harsh reaction conditions, e.g. high pressure, high temperature or Lewis acid promotion, are often required to afford the corresponding heterocycles in only poor to moderate yield [12b, 92-94]. Although a,/3-unsaturated carbonyl compounds have not been used extensively as heterodienes, considerable success has been achieved with activated enone 146 (Eq. 8.27) or with the electron-deficient tosylimine 148 (Eq. 8.28). Both dienes reacted under... 

The palladium-catalyzed elimination-cyclization reaction of biscarbamates 254 opens up a further route to nitrogen-substituted allenes (Scheme 8.68) [149]. This transformation proceeds for certain substitution patterns with surprisingly high regioselectivity, favoring allenes 256 with a terminally unsubstituted C=C bond. 

Sulfur-containing acyclic and cyclic compounds have been prepared from allenyl sulfides in numerous transformations such as substitutions, additions, cydoaddi-tions and other cyclization reactions. Like the other donor-substituted allenes, allenyl sulfides are suitable substrates for regioselective lithiation and substitutions as exemplified in Scheme 8.86 [168, 169,175]. 

The examples illustrated in the almost 100 schemes in this chapter demonstrate how versatile donor-substituted allenes can be in synthetic processes. The major applications concern addition reactions and cycloadditions to the allenic double bonds, which furnish products with valuable functional groups. Of particular interest are metalations - usually at C-l of the allene unit - followed by reactions with electrophiles that deliver compounds which can often be used for cyclization reactions. A variety of highly substituted and functionalized heterocycles arises from these flexible methods, which cannot be obtained by other reactions. Many of these transformations proceed with good regioselectivity and excellent stereoselection. 

Most, perhaps all, of the reactions that simple alkenes undergo are also available to allenes. By virtue of their strain and of the small steric requirement of the sp-hybrid-ized carbon atom, the reactions of allenes usually take place more easily than the corresponding reactions of olefins. Because the allenes can also be chiral, they offer opportunities for control of the reaction products that are not available to simple alkenes. Finally, some reaction pathways are unique to allenes. For example, deprotonation of allenes with alkyllithium reagents to form allenyl anions is a facile process that has no counterpart in simple alkenes. These concepts will be illustrated by the discussion of cyclization reactions of allenes that follows. 

Alternative, also stereoselective, routes to allenic steroids take advantage of cationic cyclization reactions [108] or [2,3]-sigmatropic rearrangements [109]. For example, the allenic Michael acceptor 112 was prepared with 57% chemical yield by reaction of mestranol (111) with diethyl chlorophosphite and was found to inhibit the sterol biosynthesis of the pathogen responsible for Pneumocystis carinii pneumonia (PCP), the most abundant AIDS-related disease (Scheme 18.36) [110]. 

The ability of (Z)-l,2,4-heptatrien-6-ynes (enyne-allenes) and the benzannulated derivatives to undergo cyclization reactions under mild thermal conditions to produce biradicals has been the main focus of their chemical reactivities [1-5]. With the development of many synthetic methods for these highly conjugated allenes, a variety of biradicals are readily accessible for subsequent chemical transformations. Cyclization of the enyne-allene 1 could occur either via the C2-C7 pathway (Myers-Saito cyclization) leading to the a,3-didehydrotoluene/naphthalene biradical 2 [6-10] or via the C2-C6 pathway (Schmittel cyclization) producing the fulvene/benzofulvene biradical 3 [11] (Scheme 20.1). 

The benzannulated enyne-allenes 48 were likewise synthesized in situ from coupling between 41b and the bromoallene 47 (Scheme 20.11) [39]. Under the reaction conditions, 48 presumably underwent a spontaneous cation-mediated Myers-Saito cyclization reaction with a concomitant 1,2-shift of the trimethylsilyl group to give the naphthalene derivatives 49. 

The use of l-iodo-9-fluorenone (59) for cross-coupling with phenylacetylene produced 60, which on treatment with 51 gave the benzannulated enyne-allenes 61 (Scheme 20.14) [43], Thermolysis of 61 in 1,4-CHD at 75 °C promoted the Myers-Saito cyclization reaction, leading to 63 in excellent yields. Again, the benzylic radical center in 62 is a stabilized triarylmethyl radical. 

The diketone 64 was also readily prepared from 59 as outlined in Scheme 20.15. Condensation between 64 and 2 equiv. of 51b gave 65 in excellent yield. Thermolysis of 65 in 1,4-CHD at 75 °C also promoted the Myers-Saito cyclization reaction to generate the biradical 66. The aryl radical center in 66 was then captured by the allenic moiety to form 67, having two stabilized triarylmethyl radical centers. Subsequent hydrogen-atom abstractions from 1,4-CHD then furnished 68. 

The benzannulated analogs were also found to behave in a similar fashion. Attachment of a pendent olefin to the benzannulated enyne-allene system as depicted in 89 allowed the aryl radical in 90 to be captured in a 5-exo radical cyclization reaction leading to 91 and then the dihydrobenz[e]indene 92 (Scheme 20.20) [55, 56]. 

The benzannulated analog 115 was likewise synthesized from 114 (Scheme 20.24) [56, 63], However, unlike 109, thermolysis of 115 resulted in its slow decomposition without the formation of the cycloaromatized adduct 116. The lack of propensity for 115 to undergo the Myers-Saito cyclization reaction was attributed to unfavorable steric interactions between the diphenylphosphinyl group and the aryl ring of the benzannulated enyne-allene system, causing the allenic moiety to be rotated out of the plane defined by the aryl ring and preventing the cyclization reaction. 

The enyne-allenylphosphine oxides 120 and the benzannulated and naphthannu-lated analogs 121 and 122 having the diphenylphosphinyl group at the allenic terminus were readily prepared from the corresponding enediynyl propargylic alcohols 117,118 and 119 (Scheme 20.25) [64]. Without the unfavorable steric interactions, these conjugated derivatives smoothly underwent the Myers-Saito cyclization reaction. 

Scheme 20.26 Schmittel cyclization reactions of benzannulated enyne-allenes.

Scheme 20.27 Schmittel cyclization reactions of tert-butyl- and trimethylsilyl-substituted enyne-allenes.

Treatment of the acetylenic ketones 186 with lithium dialkylcuprates and trapping the resultant enolates with acetic anhydride produced the enyne-allene 187 (Scheme 20.39) [72], Regeneration of the oxyanion-substituted enyne-allene system using methyllithium at -20 °C led to the formation of either the indanones 188 or the ben-zofluorenones 189 through a Schmittel cyclization reaction. 

Steiically congested cw-aziridines such as 137 were prepared from the deiivatized amino allyl alcohol precursor 136 through a palladium-catalyzed cyclization reaction <99TL1331>. This methodology has also been extended to the cyclization of amino allenes <99JOC2992>. 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

The propargylsilane group can participate in intramolecular cyclization reactions to give a five-membered ring with an exocyclic allene group. An example is the cyclization of 2 to a mixture of 3 and 4 when treated with acetic acid. 1... 

Allenes insert into ir-allyl complexes so as to generate new ir-allyl species (equation 78).248 The insertion of 2-r-butyl-1,3-butadiene into ir-allylpalladium complexes proceeds normally, but is then followed by an unusual cyclization reaction, presumably due to the disposition of the butenyl frag-... 

The synthesis of polysubstituted pyrrolidines has been achieved344 in a diastereo-selective and enantioselective manner via the zinca-ene-allene cyclization. In an extension of this work,345 the zinca-ene-allene reaction of polysubstituted enynes lithiated on the propargylic position has been used to prepare polysubstituted... 

Singleton and coworkers took up the ene cyclization reaction of ene-allene (Scheme 4) and carried out combined experimental-computational investigation.43 The ene reaction had been known to show mechanistic uncertainty, in particular whether it proceeds via a concerted or stepwise route, and therefore provided a challenge for dynamics study. KIE measurement for the reaction of 22 (Ri = R.2 = TMS) in toluene at 50°C gave kcus/kcm of 1.43, which was smaller than what was normally observed in concerted ene reactions. However, the isotope effect was too large to support a stepwise ene reaction. Thus, this was in line with the idea that the mechanism is near the concerted-stepwise borderline. 

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