Allylation and Prenylation

Indirect alkylation via Uthio-l-(phenylsulf(Miyl)indoles was more successful for making both the 2- and 3-substituted products. In the case of the 3-isomer, the lithio indole was first converted to the cuprate. The W-phenylsulfonyl group was removed by reduction. 

Both the direct magnesium allylation and the allylation via a 3-lithio indole were employed in the synthesis of 1,3-diallylindole [83]. Somewhat in contrast to Wenkert s results, both geranyl and famesyl bromide are reported to give about 30% yield of the not rearranged 3-aUylation products with indole magnesium iodide [84]. Prenylation of the magnesium salt of A -methyltryptamine proceeds with intramolecular capture of the amino group [85, 86]. 

Using Mayr s nucleophilic scale (see Sect. 1.1) as a guide, Westermaier and Mayr concluded that indole should compete with solvent for allylic cations in aqueous acetonitrile or acetone. This was shown to be the case experimentally [87]. Several allylic chlorides and bromides react with indole or 1-methylindole to provide allylation products. Unsymmetrical cations react at the less substituted position. Interestingly, significant amounts of 2-substituted indoles are generated under these conditions (usually about 10 1 for C-3 C-2). 

C-Ring substituted indoles, including 4-nitroindole, are also allylated under these conditions. The reaction is believed to proceed by an Sa I mechanism, with the Zn(03SCF3)2 acting as a Lewis acid catalyst. There may also be some N-H deprotonation by the amine. 1-Methylindole reacts under these conditions, but with reduced yield. The Zn(03SCF3)2-mediated reaction was used in tandem with intramolecular nucleophilic capture to synthesize the flustramine structure [89]. 

This cyclization has also been done using the TMS-methyl derivative of the carbamate [90]. The reaction is postulated to occur via deprotraiation and decomposition of an A -trimethylsilylmethyl intermediate at the carbamate group. 

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The addition of allyl and prenyl organometallics (84) to 8-(-)-phenylmenthyl A/-methoxyiminoacetate (83 equation 19) has been examined for the asymmetric synthesis of amino acids. Treatment of (83) with allylboronates and allylzinc bromide affords N-alkoxyamines (85) and (86 Table 19). Both allyl-... 

Useful selectivity between allyl and 3-methylbut-2-enyl (prenyl) ethers has been achieved. ... 

With allylic Grignard reagents, the carbophilic addition on the thiocarbonyl of phenylisothiocyanate occurred as expected exclusively with inversion of the allylic chain. From crotyl and prenyl magnesium halides the compounds (4f) and (4g) were obtained in yields of 77 and 72%, respectively. 

The alkylation goes well as 63 is the reactive allylic halide prenyl bromide and hydrolysis and decarboxylation occur as usual.13... 

Chiral Lewis-basic catalysts (Figs. 7.1 and 7.2), in particular phosphoramides 8-12 [9, 14c, 15c, 22-24], formamide 13 [17], pyridine N,N -bisoxides 17 and 18 [25-27], N-monoxides (19-26) [27-32], and N,N N"-trisoxides (27) [33] exhibit good to high enantioselectivities for the allylation of aromatic, heteroaromatic, and cinnamyl-type aldehydes (1) with allyl, trans- and ds-crotyl, and prenyl trichlorosilanes (2a-d). Chiral formamides (with the exception of 13, as discussed below) [17], pyridine-oxazolines [34], urea derivatives [19] and sulfoxides [35] are effective only in stoichiometric quantities (or in excess) and, as a rule, exhibit lower enantioselectivities. 

The equilibrium is entirely in favour of prenyl bromide because of its more highly substituted double bond. Reactions on the tertiary allylic isomer are very likely to take place by the S l mechanism the cation is stable because it is tertiary and allylic and the equilibration tells us it is already there. Even if the reactions were bimolecular, no mechanism would be necessary for the tertiary... 

Prenyl ethers can be formed using the typical Williamson ether synthesis—that is, by reacting the alcohol with a suitable base and a prenyl halide. Many of the methods used for the formation of allyl and benzyl ethers should be applicable. ... 

I2, CH2CI2, 3A ms, 1-8 h, rt, 22-94% yield. The Bn, allyl, and TBDMS ethers are stable to these conditions, but TBS ether is partially cleaved. Phenolic prenyl ethers react to give chromanes. 

Pd(0Ac)2, TPPTS, CH3CN, H2O, EtjNH, 96-100% yield. The allyl carbamate (alloc) group can be cleaved in the presence of the prenyl ester. These conditions will also cleave allyl carbonates, cinnamyl esters, and prenyl carbamates. ... 

In the presence of CuCN, these homoenolates react with acid chlorides to make y-ketoesters but their forte is reaction with allylic phosphates. Prenyl diethylphosphate gives 45 in good yield and the more highly substituted product 46 is formed in near quantitative yield. These are impressive results both reagents react through the y-carbon the homoenolate 43 where the Zr is and the allylic phosphate where the phosphate isn t. 

An enantioselective synthesis of amino acids has been examined using chiral nonracemic a-imino esters (36) derived from (S)-l-phenylethylamine and (-)-l-cyclohexylethylamine (equation 9, Table 9). Allyl-magnesium, -copper and -titanium reagents react at both the imine and ester carbon atoms of (36), a result of the molecule s ambient electrophilicity. The addition of allyl-, methallyl- and prenyl-9-BBN and -ZnBr to a-imino ester (36), however, generates amines (38) and (39). While the absolute stereochemistry of (38) and (39 R = Ph) has been determined (entries 1-4, Table 9), that of the cyclohexyl-ethylamine-derived products has not (entries 5-8, Table 9). 

Cleavage of C 0 bonds. Allylic ethers are cleaved at room temperature in the presence of (Ph3P)4Pd. Rates are much higher in protic solvents (MeOH vs. THF) and the cleavage of allyl, methallyl, prenyl groups in succession is possible. ... 

Remote chiral induction is performed with bicyclic thiolactams [48]. For example, the thiolactam 73 is deprotonated with LDA, and this is followed by allylation to form thiolactam 74 (Eq. 25) [48cj. The reaction with 71 (R=R =H) shows poor selectivity, whereas that with cinnamyl and prenyl bromides gives the corresponding products with high diastereoselectivity. 

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