Cycloadditions with Oxyallyl Cations

The furan nucleus undergoes cycloadditions with oxyallyl cations to produce compounds with the oxabicyclo[3.2.1]octene skeleton. Various research groups have found new ways of generating the oxyallyl cation and have also defined the types of substituted furans which undergo reaction. Reviews on this reaction have covered the literature up to 1987 [24-26]. The mechanism of the cycloaddition has been discussed in detail by Hoffmann [26]. 

A more recent development in the generation of oxyallyl cations from polybromoketones has been the use of diethylzinc [27], This procedure is convenient and amenable for the large-scale syntheses of oxabicyclic compounds. In addition, the combination of cerium (III) chloride and tin (II) chloride has been very effective in inducing the [4 + 3] cycloaddition between furan and 2,4-dibro-mopentan-3-one [28]. Sonication has also been observed to improve yields in cycloadditions promoted by zinc-copper couple [29]. 

The cycloadditions of several unusual oxyallyl cations are briefly outlined in Table 1. Tricyclic oxa-bridged substrates can be readily assembled from cyclic oxyallyl cations derived from monohalogenated cyclic ketones 14 a and LiClO/EtjN (entry 1) [30]. Dihalogenated cyclic ketones 14b can also serve as cyclic oxyallyl cation precursors when treated with diiron nonacarbonyl [31], or zinc-copper couple [32]. Cycloadditions of this type have been successful in producing oxatricyclic compounds where n = 2,3,4,5,9, although some adducts are mixtures of cis and trans isomers. 

Oxyallyl cations bearing oxygen substituents have been synthesized from 15 and catalytic TMSOTf (entry 2) [33], from 16andLiC104/Et3N (entry 3) [34], and from the reaction of pyruvaldehyde directly with SnCl4 (entry 4) [35]. Oxyallyl cations from 17 undergo cycloaddition with furan to give nitrile-substituted oxabicyclic compounds (entry 5) [34b]. 

Conjugated and homoconjugated oxyallyl cations from 18,19a, and 19b have also been trapped with furan to give cycloadducts (entries 6,7) [36]. 

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Cyclopropanones are in electrocyclic equilibrium with oxyallyl cations. The cyclopropanone is generally lower in energy, but the oxyallyl cation is not so much higher in energy that it is kinetically inaccessible. Oxyallyl cations can undergo cycloadditions, as will be discussed later. 

The synthesis of seven-membered rings from furans and a,a -dibromoketones via oxyallyl intermediates is well known. It was reported that this reaction occurs quite easily when water is used as solvent <97TL8031>. In a study on the influence of steric and electronic effects on a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations it was found that in almost all cases a c/x-diastereospecificity and a high endo diastereoselectivity is obtained <97T11669>. A tandem Peterson olefination-[4 + 3] cycloaddition reaction with furans has been reported <97JOC1578 97TL386l>. For an intramolecular [4 -t- 3] cycloaddition see <97JOC6051>. The first asymmetric [4 + 3]... 

Phosphole oxides also participate in a cycloaddition reaction with oxyallyl cations <75T53>, a process that gives rise to novel phosphatropolone structures. Preformed 1,2,5-triphenylphosphole oxide gave a derivative of the 8-phosphabicyclo(3.2.1]octan-6-ene-3-one ring system ((157), 91%). The oxyallyl cation (156) was prepared from a,a -dibromodibenzylketone and Nal in acetonitrile (Scheme 31). 

The experimental observations and outcomes of the cycloadditions of oxyallyl cations, which are the same except for the identity of M, are compared in Table 18.1. Over a series of cycloadditions with furan as the common diene, the lithium oxyallyl cation (5, M = Li), formed from chloroke-tone la under basic conditions, was not highly electrophilic. 

Intermolecular and intramolecular [4- -3] cycloadditions of oxyallyl cations with dienes are a direct and efficient strategy to assemble seven-membered rings, which are common in the carbon frameworks of natural products and pharmaceutically... 

Noyori et al., among the early developers of [4+3] cycloaddition reactions, introduced a general approach to tropane alkaloids utilizing an intermolecular [4+3] cycloaddition of pyrroles with oxyallylic cations [9,10]. This is exemplified by the synthesis of (—)-hyoscyamine 12. Heating a solution of A-carbomethoxypyrrole 2 with excess tetrabromoacetone 6 in the presence of Fe2(CO)9 resulted in the formation of diastereoisomers 7 and 8 in a ratio of 2 1, respectively (Scheme 19.3). 

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). 

A rare example of a higher-order [5 + 3]-cycloaddition was reported by Liesbeskind and Arrayas. Homochiral 7]3-pyranyl- and // -pyridinyl-molybdcnum 7r-complexes react with an oxyallyl cation that is generated in situ from the precursor 88. After decomplexation of the molybdenum, oxa- and azabicyclo[3.3.1]nonenes are obtained in moderate yields and in excellent ee s (Scheme 27).89 Related work using 3-pyranyl- and 3-pyridinyl-molybdenum 7r-complexes as five-carbon components in [5 + 2]-cycloadditions is discussed in Section 10.13.2.1.2. 

Ring opening reaction of alkylidenecyclopropanone acetals readily proceeds in the presence of Lewis or Bransted acids to produce l-alkylidene-2-oxyallyl cation, which is provided for the reaction with nucleophiles such as chloride, alcohols, siloxyalkenes, and furans. The reaction of this cation with the carbon nucleophiles gives products of [4 + 3] and [3 + 2] cycloaddition as well as those of nucleophilic addition. The modes of addition reactions are controlled by the oxy group of the cation and by the reaction conditions including solvent. 

The intramolecular 4 + 3-, 3 + 3-, 4 + 2-, and 3 + 2-cycloaddition reactions of cyclic and acyclic allylic cations have been reviewed, together with methods for their generation by thermal and photochemical routes.109 The synthetic uses of cycloaddition reactions of oxyallyl cations, generated from polybromo and some other substrates, have also been summarized seven-membered rings result from 4 + 3-cycloadditions of these with dienes.110 The use of heteroatom-stabilized allylic cations in 4 + 3-cycloaddition reactions is also the subject of a new experimental study.111 The one-bond nucleophilicities (N values) of some monomethyl- and dimethyl-substituted buta-1,3-dienes have been estimated from the kinetics of their reactions with benzhydryl cations to form allylic species.112 Calculations on allyl cations have been used in a comparison of empirical force field and ab initio calculational methods.113... 

Cycloadditions. Silver perchlorate converts the l,l-dimcthyl-2-(tri-methylsiloxy)allyl chloride (1) and related allylic chlorides into an oxyallyl cation (a), which reacts with 1,3-dienes to form seven-membered ketones, often in high yield, particularly in reactions conducted in nitromethane. 

The competing pathways in the reactions of intermediate l-alkylidene-2-oxyallyl cations (47) with furan have been investigated.54 Cycloaddition pathways compete with the electrophilic substitution pathway which initially forms the cation (48) from which a number of products may form. 

Allylsilanes act as good acceptors of nitrones and oxyallyl cations. The 1,3-dipole species arising from electronically activated cyclopropanes can be trapped by allylsilanes.203 204 2043 Epoxides as well as aziridines act as 1,3-dipole precursors for inter- and intramolecular [3 + 2]-cycloadditions with allylsilanes.205 2053 206 2063... 

Now comes the most interesting step in the whole process—a step that unites a cycloaddition and a rearrangement and sets the scene for a fragmentation. The idea was to treat the bromoketone with base to make an oxyallyl cation as an unstable intermediate. 

The oxyallyl cation with its two electrons delocalized over the allylic system would add to furan in a [2 + 4] cycloaddition to give a new cation stabilized by the oxyanion or, in more familiar guise, a ketone. The reaction was supposed to go like this. 

A number of different furan-based approaches to the synthesis of 7-membered ring systems were reported in 2003. In the novel example shown below, the furan participated in an intramolecular [4+3] cycloaddition with nitrogen-stabilized chiral oxyallyl cation to form polycyclic structures <03JA12694>. Attempts to construct the [4.4.1] bicychc BC ring system of ingenol via a type-II intramolecular [4+3] cycloaddition between furan and an oxyallyl cation produced the desired product but only in 14% yield <03JOC7899>. 

Much attention has been directed to the chemistry of p-heteroatom-substituted allylic cations (5), especially oxyallyl cations (7), from both synthetic and mechanistic viewpoints. One of the characteristic reactions of oxyallyls (7) is their [4 -i- 3] 7 cycloadditions with conjugated dienes, which provide a... 

The [4+3]-cycloaddition of furan to the l,3-dihromo-2-oxyallyl cation generates, after dehalogenation with the zinc/copper couple, 8-oxahicyclo[3.2.1]oct-6-en-3-one (325). It... 

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