Allylic substitution intramolecular reaction

Scheme 29 Sequential intramolecular allylic substitution-Heck reaction [82]...

A series of substituted coumestans 87 were synthesized by Liu, Wang, and coworkers through the formal [3 + 2] cycloaddition of quinone monoketals 85 and the thiomethyl-substituted coumarin 86 (Scheme 39) [138]. The reaction, catalyzed by tin tetrachloride, involves an allylic substitution/intramolecular cyclization/thiol elimination sequence. 

Indene derivatives 264a and 264b are formed by the intramolecular reaction of 3-methyl-3-phenyl-l-butene (263a) and 3,3,3-triphenylpropylene (263b) [237]. Two phenyl groups are introduced into the /3-substituted -methylstyrene 265 to form the /3-substituted /3-diphenylmethylstyrene 267 via 266 in one step[238]. Allyl acetate reacts with benzene to give 3-phenylcinnamaldehyde (269) by acyl—O bond fission. The primary product 268 was obtained in a trace amount[239]. 

Intramolecular reaction of the allenyl carbamate 5 in the presence of a large excess of allylic chloride catalyzed by Pdi(dba)3 or PdCl2(PhCN)2 affords the substituted oxazolidin-2-one 6. Since the reaction is catalyzed by both Pd(II) and Pd(0), its mechanism is not dear[3]. 

Nanaomycin A 103 and deoxyfrenolicin 108 are members of a group of naphthoquinone antibiotics based on the isochroman skeleton. The therapeutic potential of these natural products has attracted considerable attention, and different approaches towards their synthesis have been reported [65,66]. The key step in the total synthesis of racemic nanaomycin A 103 is the chemo-and regioselective benzannulation reaction of carbene complex 101 and allylacety-lene 100 to give allyl-substituted naphthoquinone 102 after oxidative workup in 52% yield [65] (Scheme 47). The allyl functionality is crucial for a subsequent intramolecular alkoxycarbonylation to build up the isochroman structure. However, modest yields and the long sequence required to introduce the... 

A comparison of several of the PY and IM types of catalysts in intramolecular reactions of allylic diazoacetates led to a consistent model for the enantioselectivity. The highest e.e. values are observed for ds-substituted allylic esters. Both R and R1 are directed toward the catalyst and introduce steric interactions that detract from enantioselectivity.208... 

As shown in Scheme 2.20, selective lithiation of substrate 2-87 by treatment with LDA in THF at -78 °C triggers an intramolecular Michael/intermolecular aldol addition process with benzaldehyde to give a mixture of diastereomers 2-90 and 2-91. 2-91 was afterwards transformed into 2-92, which is used as a chiral ligand for Pd-catalyzed asymmetric allylic substitution reactions [29]. 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

Allylic CH bonds can be substituted fairly regioselectively by using an intramolecular reaction (Eq. 12) [80] or suitable substitution (Eq. 13) [81]. 

Several types of intramolecular allylic substitution reactions of carbon, nitrogen, and oxygen nucleophiles catalyzed by metalacyclic iridium phosphoramidite complexes have been reported. Intramolecular allylic substitution is much faster than the competing intermolecular process when conducted in the presence of iridium catalysts. Thus, conditions involving high dilution are not required. Intramolecular... 

Allylic acetates in conjunction with phosphinooxazolines (PHOX) as chiral ligands were used for the first asymmetric Ir-catalyzed allylic substitution (Scheme 9.7) [5]. The reaction was slow, compared to that catalyzed by the [lr(COD)Cl]2/P(OPh)3 system or the parent complex [lr(COD)Cl]2, although both regioselectivity and enantioselectivity were very high. The aminations were generally slow, yet quite interesting results were achieved in intramolecular aminations nevertheless [17, 18] in particular, a very strong influence of halide salts was found. 

Less extended investigations have been carried out for the stereochemistry of further substitution reactions, which mostly proceed with lower regioselectivities a-carboxylation (inversion) reaction with methyl chloroformate in the a-position (inversion) a-acylation by 2,2-dimethylpropanoyl chloride (inversion)" y-methylation by methyl iodide (anti-S g) and methyl triflate syn-S f° , intramolecular reactions with allyl chlorides (a, inversion or y, awh -S see Section IV.C.3). 

Intramolecular reactions of 3-(2- and 3-thienyl)allyl phenylpropiolates 311 and 312 gave lactones 313 and 314. Formation of 313 involves substitution into the 3-position of the thiophene, while formation of 314 involves substitution into its 2-position (65JHC225). 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

The 3(2H)-furanones are - as the other 4-hetero-2-cyclopentenones - normally 2,2-disubstituted to avoid enolization to the respective 3-hydroxyfuran. If one of the substituents is an alkenyl side chain, then intramolecular [2 + 2]-photocydoaddition reactions are possible with the regioselectivity being dependent on the chain length (Scheme 6.20). The allyl-substituted substrate SO (n— 1) gave predominantly the formal straight product SI [62], while the butenyl-substituted substrate 50 (n = 2) resulted in formation of the crossed product 52 [63]. 

Furthermore, following an analogous methodology, combining the Morita-Baylis-Hillman reaction and the Trost-Tsuji reaction, Krische and co-workers have obtained allyl-substituted cyclopentenones 94 [84], Reaction was initiated by Michael addition of tributyl phosphine to an enone moiety 92, generating a latent enolate 93 which reacts intramolecularly with a jr-allylPd complex as the electrophile partner. A final -elimination step of trib-utylphosphine, favored by the presence of the methoxide ion, delivered the substituted cyclopentenones 94 (Scheme 36). 

The Heck reaction may also proceed in an intramolecular fashion if the aryl halide is covalently bound to the allyl substrate. In this case the sequential allylic substitution-Heck-cyclization with Pd acetate as a catalyst takes place very smoothly as an unimolecular process and furnishes the polycon-densed pyrrolidones 91 in excellent yields (Scheme 29). 

An intriguing showcase for polycyclizations based upon hetero-domino reactions is outlined in Scheme 30, where the catalyst 89 gives rise to the formation of a mixture of indolone skeletons 92-94 with a preference for the generation of tetracycle 94 as a result of an intramolecular allylic substitution-Heck sequence. 

In route A, one electron is removed from one double bond to generate a cation radical, and subsequent transarmular reaction of the cation radical widi die odier double bond forms a new carbon-carbon bond. On the odier hand, in route B, allylic substitution or oxidative addition at one double bond takes place widiout intramolecular interaction between the double bonds. As exemplified by the anodic oxidation of... 

S)-l is obtained from the bis(methyl carbonate) of (Z)-2-butene-l,4-diol and l,2-bis(tosyl-amino)ethane through a tandem pa]ladium(0)-catalyzed allylic substitution in the presence of (R)-BINAP (I) as chiral ligand79. Equilibration of the 7t-allylpalladium intermediates formed before the intramolecular nucleophilic attack is necessary for high enantioselectivity. Thus, only a racemic piperazine is produced in the reaction of the more nucleophilic l,2-bis(benzyl-amino)ethane with the diacetate of (Z)- or ( )-2-butene-l,4-diol. 

---