Allylic basic conditions

Torgov introduced an important variation of the Michael addition allylic alcohols are used as vinylogous a -synthons and 1,3-dioxo compounds as d -reagents (S.N. Ananchenko, 1962, 1963 H. Smith, 1964 C. Rufer) 1967). Mild reaction conditions have been successful in the addition of ],3-dioxo compounds to vinyl ketones. Potassium fluoride can act as weakly basic, non-nudeophilic catalyst in such Michael additions under essentially non-acidic and non-basic conditions (Y. Kitabara, 1964). 

Allylation under basic conditions. Allylation can be carried out under basic conditions with allylic acetates and phosphates, and under neutral conditions with carbonates and vinyloxiranes. The allylations under neutral conditions are treated separately in Section 2.2.2.1 from those under basic conditions. However, in some cases, allylations of the same substrates are carried out under both basic and neutral conditions to give similar results. These reactions are treated together in this section for convenience. Allylic acetates are widely used for Pd-catalyzed allylation in the presence of bases tertiary amines or NaH are commonly used[6,7,4l]. As a base, basic alumina or ICF on alumina is conveniently used, because it is easy to remove by filtration after the reaction[42]. Allyl phosphates are more reactive than acetates. The allylation with 40 proceeds stepwise. At first allylic phosphate reacts with malonate and then allylic acetate reacts with amine to give 41(43]. 

Wylation under neutral conditions. Reactions which proceed under neutral conditions are highly desirable, Allylation with allylic acetates and phosphates is carried out under basic conditions. Almost no reaction of these allylic Compounds takes place in the absence of bases. The useful allylation under neutral conditions is possible with some allylic compounds. Among them, allylic carbonates 218 are the most reactive and their reactions proceed under neutral conditions[13,14,134], In the mechanism shown, the oxidative addition of the allyl carbonates 218 is followed by decarboxylation as an irreversible process to afford the 7r-allylpalladium alkoxide 219. and the generated alkoxide is sufficiently basic to pick up a proton from active methylene compounds, yielding 220. This in situ formation of the alkoxide. which is a... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Trichlorosilanc reacts with allyl halides under mildly basic conditions, subsequent treatment with methylmagnesium bromide giving rise to allyl(trimethyl)silanes15-16. 

Nucleophilic addition to allenyl sulphoxides 547 proceeds across the a, /(-double bond to produce the corresponding )3-substituted allylic sulphoxides which undergo readily a [2,3]-sigmatropic rearrangement affording substituted allyl alcohols (equation 345). Under proper basic conditions, the initially formed allylic sulphoxides can rearrange to the corresponding vinyl sulphoxides which can be elaborated to 2,4-dienones 549 (equation 346) and a-ketosulphoxides (equation 347) . ... 

Allylic hydroxycrotyl-oligoethylene glyco-n-alkanoyl (HYCRON) linker 25 was applied to the synthesis of protected peptides and glycopep-tides [31]. HYCRON is stable to both acidic and basic conditions and is compatible with Boc- and Fmoc-based chemistry. The preparation of this novel linker is only two steps from commercially available materials. H YCRON linker can be cleaved under neutral conditions using Pd catalyst (Scheme 9). 

Conjugated nitroalkenes are isomerized to allylic nitro compounds under basic conditions. Reactions of a,P-unsaturated nitro compounds with aldehydes under basic conditions lead directly to y,8-unsaturated P-nitro alcohols (Eq. 3.24). 3 This reaction is very useful for preparing allylic nitro compounds. 

A somewhat related microwave-promoted 5 -0-allylation of thymidine has been described by the Zerrouki group (Scheme 6.108) [215], While the classical method for the preparation of 5 -0-allylthymidine required various protection steps (four synthetic steps in total), the authors attempted the direct allylation of thymidine under basic conditions. Employing sodium hydride as a base at room temperature in N,N-dimethylformamide resulted in the formation of per-allylated compounds along with the desired monoallylated product (75% yield). The best result was achieved when both the deprotonation with sodium hydride (1.15 equivalents) and the subsequent allylation (1.2 equivalents of allyl bromide) were conducted under... 

Allyl sulphones can be converted to dienes by alkylation and elimination of sulphinic acid under basic conditions (equation 64)105. Several vitamin A related polyenes have been synthesized following this two-step protocol (Table 10)106. The poor leaving-group ability of the arylsulphonyl group requires treatment with strong base for elimination. However, elimination of the allylsulphonyl group takes place readily under palladium catalysis (equation 65)107. Vinyl sulphones can be converted to dienes via Michael addition, alkylation with allyl halides and elimination of sulphinic acid sequence (equation 66)108. 

Monomer Synthesis. 4-Allyloxystyrene was prepared by the Wittig reaction of 4-allyloxybenzaldehyde and methyltriphenylphosphonium bromide, under basic conditions. The allyloxybenzaldehyde was prepared, in turn, by the alkylation of 4-hydroxybenzaldehyde with allyl bromide. This method, which provides high purity monomer in high overall yield, is outlined in Scheme 1 and has been previously described (2). Alternatively, the monomer may be prepared by the direct alkylation of p-vinylphenol with allyl bromide (8,9), although this method is less convenient due to the difficulties in synthesizing and storing the highly reactive vinyl phenol (10). 

An interesting approach to the pyrrolizidine skeleton was devised wherein pyrrole-2-carboxaldehyde (70) underwent A-allylation under basic conditions and subsequent olefmation with ethyl p-tolylsulfinylmethanephosphonate to produce the pyrrolyl alkene 71 <00TL1983>. Intramolecular Heck reaction of the iodo species then produced the 1 -p-tolylsulfinyl-1,3-diene 72. 

This finding is the consequence of the distribution of various ruthenium(II) hydrides in aqueous solutions as a function of pH [RuHCl(mtppms)3] is stable in acidic solutions, while under basic conditions the dominant species is [RuH2(mtppms)4] [10, 11]. A similar distribution of the Ru(II) hydrido-species as a function of the pH was observed with complexes of the related p-monosulfo-nated triphenylphosphine, ptpprns, too [116]. Nevertheless, the picture is even more complicated, since the unsaturated alcohol saturated aldehyde ratio depends also on the hydrogen pressure, and selective formation of the allylic alcohol product can be observed in acidic solutions (e.g., at pH 3) at elevated pressures of H2 (10-40 bar [117, 120]). (The effects of pH on the reaction rate of C = 0 hydrogenation were also studied in detail with the [IrCp (H20)3]2+ and [RuCpH(pta)2] catalyst precursors [118, 128].)... 

It is interesting to note that this methodology allows the preparation of 4-functionalized indole derivatives starting from a simple acyclic precursor in a one-pot sequence. To prepare N-unsubstituted indoles, we choose the allyl moiety as a result to its stability to strong basic conditions and the variety of methods for its removal.[20] We therefore used an approach based on the isomerization/hydrolysis of the allyl groups with diisobutylaluminium hydride (DIBAL-H) and a... 

The chiral 1,3-divinylallene (1,3,4,6-heptatetraene) (3) is obtained when the vinylace-tylene Grignard reagent 198 is first coupled to allyl bromide (199) and the resulting skipped enyne is subsequently isomerized under basic conditions (Scheme 5.29) [74]. 

Still, occasionally the other fuctional groups react as well, for example in 38 under basic conditions the propargylic alcohol isomerizes to the a,/3-unsaturated ketone [73] (Scheme 1.15), whereas in a closely related substrate from the synthesis of a subunit of compactin an allylic alcohol remains unchanged [74],... 

Under basic conditions, a-nitroalkenes function as synthetic equivalents of allylic nitro compounds 3-nitro-3-hexene, for instance, reacts with piperidine in the presence of Pd(PPh3)4, to give 2-piperidinyl-3-hexene (equation 139)459. 

Alkynes react with haloethenes [38] to yield but-l-en-3-ynes (55-80%), when the reaction is catalysed by Cu(I) and Pd(0) in the presence of a quaternary ammonium salt. The formation of pent-l-en-4-ynes, obtained from the Cu(I)-catalysed reaction of equimolar amounts of alk-l-ynes and allyl halides, has greater applicability and versatility when conducted in the presence of a phase-transfer catalyst [39, 40] although, under strongly basic conditions, 5-arylpent-l-en-4-ynes isomerize. Symmetrical 1,3-diynes are produced by the catalysed dimerization of terminal alkynes in the presence of Pd(0) and a catalytic amount of allyl bromide [41]. No reaction occurs in the absence of the allyl bromide, and an increased amount of the bromide also significantly reduces the yield of the diyne with concomitant formation of an endiyene. The reaction probably involves the initial allylation of the ethnyl carbanion and subsequent displacement of the allyl group by a second ethynyl carbanion on the Pd(0) complex. 

The phase-transfer catalysed reaction of nickel tetracarbonyl with sodium hydroxide under carbon monoxide produces the nickel carbonyl dianions, Ni,(CO) 2- and Ni6(CO)162, which convert allyl chloride into a mixture of but-3-enoic and but-2-enoic acids [18]. However, in view of the high toxicity of the volatile nickel tetracarbonyl, the use of the nickel cyanide as a precursor for the carbonyl complexes is preferred. Pretreatment of the cyanide with carbon monoxide under basic conditions is thought to produce the tricarbonylnickel cyanide anion [19], as the active metal catalyst. Reaction with allyl halides, in a manner analogous to that outlined for the preparation of the arylacetic acids, produces the butenoic acids (Table 8.7). 

Acetylation occurs at the 2-position of allene systems (Scheme 8.14). The intermediate 7t-allyl complex breaks down via the nucleophilic displacement of the cobalt carbonyl group by the hydroxide ion to produce the hydroxyketone (7) [ 11 ]. An alternative oxygen-initiated radical decomposition of the complex cannot, however, be totally precluded. The formation of a second major product, the divinyl ketone (8), probably arises from direct interaction of the dicobalt octacarbonyl with the allene and does not require the basic conditions. 

The [2,3] sigmatropic Wittig reaction, as exemplified by the rearrangement of fluorenyl allyl ethers under solidrliquid basic conditions is catalysed by tetra-n-butyl-ammonium bromide [14]. 

Employing iminophosphoranes to protect a group labile under alkaline conditions can lead to a dramatic increase in yield. This is exemplified by the transformation of allylic azide 31 into the corresponding iminophos-phorane 32 shown in Scheme 16. Hydrolysis under basic conditions leads finally to 4-amino-3-hydroxycyclohexa-l,5-diene-l-carboxyclic acid (33) in 80% yield. However, when the same azide (31) is converted with a Lindlar catalyst, via allylic amine 34 into carboxylic acid 33, only 0-30% yields are found as a consequence of the low stability of the allylic amine [93JCR(S)148]. 

Acylals (geminal diacetates) are frequently used as protecting groups for aldehydes because of their stability to neutral and basic conditions [8]. In addition, the acylal functionality can be converted into other useful functional groups [9]. For example a novel synthesis of chiral allylic esters has been developed using palladium-catalyzed asymmetric allylic alkylation of gem-diesters [10]. The allylation of... 

The procedure described illustrates a new general synthetic method for the preparation of (E)-3-allyloxyacryl ic acids and their conversion to a-unsubstituted y,5-unsaturated aldehydes by subsequent Claisen rearrangement-decarboxyl at ion. Such aldehydes are traditionally prepared by Claisen rearrangements of allyl vinyl ethers. Allyl vinyl ethers are typically prepared by either mercury-catalyzed vinyl ether exchange with allylic alcohols or acid-catalyzed vinylation of allylic alcohols with acetals. The basic conditions required for alkoxide addition to the betaine to produce carboxyvinyl allyl ethers, as described in this report, nicely complements these two methods. In addition, this Claisen rearrangement is an... 

Allyl aryl ethers are used for allylation under basic conditions[6], but they can be cleaved under neutral conditions. Formation of the five-membered ring compound 284 based on the cyclization of 283 has been applied to the syntheses of methyl jasmonate (285)[15], and sarkomycin[169]. The trisannulation reagent 286 for steroid synthesis undergoes Pd-catalyzed cyclization and aldol condensation to afford CD rings 287 of steroids with a functionalized 18-methyl group[170]. The 3-vinylcyclopentanonecarboxylate 289, formed from 288, is useful for the synthesis of 18-hydroxyestrone (290)[ 171]-... 

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