Allyl cyclization

The oxazolidin-2-ones 53 (R = H=CCH=CH2 or COEt) are obtained in a one-pot reaction of amino alcohol carbamates 52 with sodium hydroxide, followed by allyl bromide or propi-onyl chloride (94TL9533). A modified procedure for the preparation of chiral oxazolidin-2-ones 56 from a-amino acids 54, which avoids the hazardous reduction of the acids with borane and the intermediacy of water-soluble amino alcohols, is treatment of the methyl ester of the amino acid with ethyl chloro-formate to give 55, followed by reduction with sodium borohydride and thermal ring-closure of the resulting carbamate f95SC561). The 2-prop-ynylcarbamates 57 (R = Ts, Ac, Bz, Ph or allyl) cyclize to the methyleneoxazolidinones 58 under the influence of silver cyanate or copper(I) chloride/triethylamine (94BCJ2838). 

A one-pot procedure for the palladium-catalyzed allylation/cyclization of o-alkynyltrifluoroacetanilides 57a [57] and o-alkynylphenols 57b [58] was developed by Cacchi et al. (Scheme 20). This method provides a valuable tool for the synthesis of 2-substituted-3-allylindoles 58a and 2-substituted-3-allylbenzofurans 58b. It was reported that reaction proceeded through the formation of X-allyl derivatives, which form 7r-allylpalladium species 59. A subsequent rearrangement of 59 would then lead to the 7r-allylpalladium species 60. Intramolecular nucleophilic attack of the hetero atom across the activated carbon-carbon triple bond in 60, followed by reductive elimination of Pd(0) gives the products 58. A similar reaction was reported by Balme et al. [59]. 

Cationic palladium-catalyzed addition of arylboronic acids to nitriles for the formation of benzo[h]furans was reported <06OL5987>, an example of which is illustrated in the following scheme. The palladium-catalyzed cross coupling of alkynes with appropriately substituted aryl iodides for the synthesis of substituted dibenzofurans in moderate to excellent yields was also achieved <06JOC5341>. The benzo[fc]furan core of heliannuls G and H were constructed by a palladium-catalyzed Ji-allyl cyclization reaction <06TL7353>. The palladium-catalyzed oxidative activation of arylcyclopropanes was applied to the synthesis of 2-substituted benzo[Z>]furans <06OL5829>. 

Intermolecular hydroamination of alkynes, which is a process with a relatively low activation barrier, has not been used for the synthesis of chiral amines, since the achiral Schiff base is a major reaction product. However, protected aminoalkynes may undergo an interesting intramolecular allylic cyclization using a palladium catalyst with a chiral norbomene based diphosphine ligand (Eq. 11.9) [115]. Unfor tunately, significantly higher catalyst loadings were required to achieve better enantioselectivities of up to 91% ee. 

Pd-catalyzed allylic cyclization reactions with allenes... 

Other methodologies capable of cyclizing 1,6 dienes require the use of precious metals. Pd allyls cyclize these dienes to unsaturated products [117], and Ru and Rh catalysts cyclize heterocycle-substituted dienes [118]. Murai s method functions by the mechanism proposed in Scheme 1.13). 

Allylation of amines. Trost and Genet have synthesized several ring systems characteristic of alkaloids by intramolecular allylation (cyclization) of amines catalyzed by Pd(0). 

Scheme 4 Ni(0)-catalyzed intramolecular allylic cyclization of o>dienyl aldehydes 11 using hydrosilanes as a reducing agent...

SCH EME 2 Synthesis of (H-)-prosopmine (5) and (+)-prosophylline (6) using Ir-catalyzed allylic cyclization. 

Cascade Reactions. As the title compound is able to facilitate such a variety of synthetic steps, it is possible to envision a system where multiple steps are catalyzed in tandem in the same flask. The allylation-cyclization of phenols with prenyl acetate is an example of that type of reaction, involving the sequential activation of the ester and the alkene toward nucleophilic attack by two positions on the phenol (eq 38). ... 

Reaction with Allylic and Benzylic Electrophiles. The acyl radicals can be trapped with halogen- and silicon-based electrophiles. a -Allylation of a, -unsaturated ketones is done while using Mn(OAc)3 dihydrate and allyl bromide in refluxing benzene (eq 29). Better yields are usually observed for cyclopen-tenones compared to cyclohexenones. a -Benzylation is also possible using benzyl bromide as the electrophilic partner (eq 30). Both methods tolerate a range of substitution, including 8-alkoxy-a, -unsaturated ketones. It is possible to perform a sequential allylation/cyclization with an excess of allyltrimethylsilane (eq 31). Mn(OAc)3 offers good conversions, but the use of ceric ammonium nitrate (CAN) as co-oxidant improves yields. 

Scheme 73 Jt-Allyl cyclizations to the pachastrissamine tetrahydrofuran by Passiniemi and Koskinen [79]...

Koskinen et al. have employed Pd-catalyzed tr-allyl cyclizations to generate tetrahydrofurans including the tetrahydrofuran present in the cytotoxic natural product pachastrissamine (Scheme 73) [79]. From Z-allyl acetate 277 they were able to generate tetrahydrofuran 278 as the major product in 59 % yield. Interestingly, they found the stereochemistry adjacent to the alkene to be an important factor in the selectivity. The use of the sy -isomer 279 resulted in the generation of tetrahydrofuran 280 in 81 % yield with 9 1 diastereoselectivity. Tetrahydrofuran 278 was subsequently transformed into pachastrissamine. 

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