Allenes 4+2 cycloaddition reactions

Kanematsu K. Molecular Design and Syntheses of Biologically Active Compounds Via Intramolecular Allene Cycloaddition Reaction Strategy Rev. Heteroat. Chem. 1993 9 231-259... 

The IMDA-Grob fragmentation strategy that starts with an allene cycloaddition reaction is illustrated in Scheme 43. The allene-furan cycloadduct was formed together with the other exoadduct which had the opposite configuration at the i-propyl group. Partial isomerization of the other product into the thermodynamic product shown and conversion into the 10-membered ketone constituted a formal synthesis of periplanone-B <88TL650l> since that ketone had been used in an... 

The functionalized allene, DIMETHYL 2,3-PENTADIENEDIOATE, the first in the series, is an intriguing substrate for various addition and cycloaddition reactions. Finally, a new reagent, DI-ferf-BUTYL DICARBONATE, for he formation of A-f-BOC derivatives which eliminates the use o the hazardous fert-BUTYL AZIDOFORMATE (WARNING) is intrqduced. 

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

Reversible pyridine dissociation yields the non-Lewis base stabilized imido complex [Cp(NHAr) Ti=NAr] (54). This coordinatively unsaturated species undergoes a [2 + 2] cycloaddition reaction with allene to give an azatitanocyclobutane (55), which is then protonated to the /mamido complex. Elimination of enamine occurs followed by isomerization to the energetically more favorable imine. 

The study of the intramolecular nitrile oxide—allene cycloaddition shows, in particular, that dehydration of nitroallene 339 by PhNCO, generates a nitrile oxide in situ, which gives isoxazoline 340 (Scheme 1.36). Thus, the reaction of the more remote double bond with the formation of six-membered ring prevails (405). 

Allene is a versatile functionality because it is useful as either a nucleophile or an electrophile and also as a substrate for cycloaddition reactions. This multi-reactivity makes an allene an excellent candidate for a synthetic manipulations. In addition to these abilities, the orthogonality of 1,3-substitution on the cumulated double bonds of allenes enables the molecule to exist in two enantiomeric configurations and reactions using either antipode can result in the transfer of chirality to the respective products. Therefore, the development of synthetic methodology for chiral allenes is one of the most valuable subjects for the synthetic organic chemist. This chapter serves as an introduction to recent progress in the enantioselective syntheses of allenes. Several of the earlier examples are presented in excellent previous reviews [ ] ... 

Allene (1) and its alkyl and aryl derivatives have long been used in organic synthesis, especially in cycloaddition reactions, whether these are thermally [5] or photochemi-cally induced and involve metal catalysis or polar reagents [2], Potentially more interesting derivatives arise when the allene group is connected with other unsaturated building blocks as shown in Scheme 5.1. 

Zecchi and co-workers also reported 1,3-dipolar cycloadditions with nitrogen-substituted allenes. As illustrated in Scheme 8.75, the expected isoxazoline derivatives 285 were obtained by [3 + 2] cycloaddition reaction of aminoallenes 246 and nitrile oxide 284 [141, 142], Bis-adducts 286 became the major products when 2equiv. of nitrile oxide 284 were applied with prolonged reaction times. 

The heat of hydrogenation of one carbon-carbon double bond of allene is 41 kcal mol-1, whereas that of an ordinary alkene is around 29 kcal mol-1. Thus the cumulated double bond of allene liberates 12 kcal mol-1 more than that of a simple alkene on hydrogenation. Accumulation of two carbon-carbon double bonds imparts an extra reactivity to allene, making it a remarkably active component participating in a variety of cycloaddition reactions as a two-carbon unit. 

This chapter focuses on cycloaddition reactions in which at least two new cr-bonds are formed between allene derivatives and other unsaturated organic molecules. Intramole-cular cycloaddition reactions are also described. The reactions are categorized according to assembly modes, such as [m + n]-cycloaddition, where the variables m and n simply denote the number of atoms that each component contributes to the ring construction. Some electrocyclic reactions of allene derivatives are also included. 

Other examples are given in Table 12.3. The cycloaddition reactions take place even at 0 °C. A regioisomeric mixture was obtained from 1,1-dimethylallene [50]. As for the mechanism of the allene-ketene [2 + 2]-cycloaddition, it is not clear whether the reaction proceeds via a concerted process (ketene antrafacial) or a two-step process. 

Although an intramolecular thermal [2 + 2] allene-ketene cycloaddition reaction was reported, the regioselectivity was moderate [55]. 

The [2 + 2]-cycloaddition reactions of l,3-di-tert-butylallene-l,3-dicarbonitrile (go) with imines afford azetidines [60]. The nitrogen atom of the imine was attached to the central carbon atom of the allene to give 2-methyleneazetidines. 

The [3 + 2]-cycloaddition reactions of allenes with 1,3-dipoles are useful for the construction of a variety of five-membered heterocycles with a high degree of regio- and stereochemical control [67]. Generally, the dipolar cycloaddition reactions are concerted and synchronous processes with a relatively early transition state. The stereoselectivities and regiochemistries are accounted for by the FMO theory The reaction pathway is favored when maximal HOMO-LUMO overlap is achieved. 

The Lewis acid-promoted [4+ 2]-cycloaddition reaction of the allenic ester 103 having a camphor-derived chiral auxiliary with cydopentadiene provided the adduct with excellent Jt-facial selection, leading to an enantioselective synthesis of (-)-/l-san-talene [92]. 

Both uncatalyzed and catalyzed [4+2]-cycloaddition reactions of furans with the allenic esters have been reported (Table 12.6) [93]. The allene adds from the less hindered C1-C2 Jt-face. The unfavorable steric interaction between the a-hydrogen atom of the furan and the methyl group at C4 of the allene is responsible for this selectivity. The more reactive 2-methylfuran adds to the allenic ester also in a regio-selective manner. The C2 carbon atom of 2-methylfuran was exclusively attached to the Cl carbon atom of the allenic ester, providing a mixture of endo- and exoadducts. 

Table 12.6 Uncatalyzed and catalyzed cycloaddition reactions of furans with allenic esters...

Allenic ketones undergo a thermal cycloaddition reaction with 1,3-dienes. The carbon-carbon double bond proximal to the carbonyl group reacts exclusively as in the case of allenic esters [105]. 

The [4+2]-cycloaddition reaction of allenyl phenyl sulfone 130a with cyclopenta-diene afforded a mixture of mdo and exo adducts (65 35) (Table 12.8). The corresponding trichloromethyl sulfone 130b reacted at a lower temperature to give better mdo selectivities. The allene 133 possessing two sulfonyl groups was also reactive [110, 114],... 

The cycloaddition of allenes carrying an electron-withdrawing phosphorus substituent has also been studied [118]. Allenyl phosphine oxide 138 is prepared in a manner analogous to allenyl sulfoxide. The [4+ 2]-cycloaddition reaction of 138 with cyclopentadiene proceeded with a high endo selectivity. 

Intramolecular [4 + 2]-cycloaddition reactions of allenic acids and esters proceeded in refluxing toluene to give bicyclic compounds with the exo-isomer predominating (Table 12.9) [120]. When a Lewis acid was used as a promoter, the [4 + 2]-cydoaddi-tion occurred at 0 °C and the endo-isomer was favored. 

Table 12.9 Cycloaddition reactions of allenic acids and esters.

Cycloaddition reactions of electron-rich allenes with some heterodienes take place at the C1-C2 bond of the allene to yield heterocycles, a,Unsaturated carbonyl compounds 185 react with the internal C=C bond of ethoxyallene to afford dihydro-pyrans in moderate yields [150]. 

Epoxidation of amidoallenes with dimethyldioxirane leads to allene oxides as reactive intermediates which can be trapped with dienes in a [4+ 3]-cycloaddition reaction. Exposure of a mixture of amidoallene 177 with cydopentadiene to a small excess of dimethyldioxirane at -45 °C produced endo-bicydooctanone 178 in 60% yield (Eq. 13.60) [69]. The allene oxide is electrophilic, since no reaction takes place with methyl acrylate. 

An allene is a very promising unsaturated partner in cobalt-mediated [2 + 2 + 2]-cycloaddition reactions. Exposure of an allenediyne to a stoichiometric amount of CpCo(CO)2 in boiling xylenes under irradiation for 5 h furnishes red-brown complexes in 42% isolated yield (Scheme 16.76) [84—87]. Treatment of a 7 3 mixture of the two diastereomers thus obtained with silica gel provides an oxygen-sensitive cobalt-free tricydic compound. 

A tremendous number of transformations of allenes have been reported owing to their high jt-coordination ability towards transition metals. Among them, intramolecular cycloaddition reactions of allenes, in particular, appear to be a practical means of carbon-carbon bond formation in a complicated system. The allenic moiety, however, should be precisely designed for the synthetic purpose of more complex frameworks. A formidable challenge is the synthesis of diversely functionalized allenes of high chemical and/or enantiomerical purity. 

Some of the earliest applications of allenes in natural product synthesis involved thermal- and photo-induced cycloaddition reactions. As a consequence of this and the fact that these types of reactions work so well, the use of allenes as cycloeducts in these types of reactions has been widespread. A variety of examples are showcased in the sections that follow. 

Scheme 20.31 Intramolecular [2 + 2]-versus [4 + 2]-cycloaddition reactions of benzannulated enyne-allenes.

The nature of the substituents on the allene can have an impact on the outcome of a [2 + 2] cycloaddition reaction, as was illustrated by the Lewis acid catalyzed cycloadditions of l-thioaryl-3,3-dimethylallene (24) and 1 -methyl- 1-trimethylsilylallene to various 2-alkoxy-p-benzoquinones 25 (e.g. equation 8)17. The reactions were considered to proceed via carbocation intermediates formed by nucleophilic attack of the thioallene on the Lewis acid activated quinone. At lower temperatures, these carbocations closed to cyclobutanes 26, whereas at higher temperatures, the thermodynamically more stable benzofurans 27 were formed. 

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