Substitution chemoselective

In alkylbenzenes, the ortho- and para-H atoms or the benzyl CH atoms can be replaced by Brr Chemoselective substitutions in the ortho- and para-positions succeed at low temperature in the presence of a catalyst. Figure 5.15 shows an example. Chemoselective substitutions with Br2 in the benzyl position are possible using radical chemistry (see Figure 1.24), that is,... 

The carbonate group can be chemoselectively substituted in the presence of an allyl acetate58. 

The relative reactivity of the derivatives follows the trend allyl carbonate > allyl phosphate > allyl acetate (see Equations 20.5-20.7)." This difference in reactivity allows for chemoselective substitutions of one allylic alcohol derivative over another. Other allylic electrophiles, such as allylic sulfonates, which undergo cleavage of the carbon-sulfur bond, allylic nitro compounds, which undergo cleavage of the C-N bond, - and allylic... 

Allylic Halides AUyl chlorides are among the most reactive allylic substrates. As such, they should not be prone to epimerization at the state of the jT-allyl-Pd complexes, and chemoselective substitutions are possible with allylic halides/acetates [70], If halogenated dienes such as 73 are used, the protocol gives access to substituted aUenes 74 [71] (Scheme 12.37). 

With higher alkenes, three kinds of products, namely alkenyl acetates, allylic acetates and dioxygenated products are obtained[142]. The reaction of propylene gives two propenyl acetates (119 and 120) and allyl acetate (121) by the nucleophilic substitution and allylic oxidation. The chemoselective formation of allyl acetate takes place by the gas-phase reaction with the supported Pd(II) and Cu(II) catalyst. Allyl acetate (121) is produced commercially by this method[143]. Methallyl acetate (122) and 2-methylene-1,3-diacetoxypropane (123) are obtained in good yields by the gas-phase oxidation of isobutylene with the supported Pd catalyst[144]. 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

DIBAL, NiCl2(dppp), toluene, CH2CI2, THF, or ether, 80-97% yield. These conditions are chemoselective for simple alkyl and phenolic allyl ethers. More highly substituted allyl ethers are unreactive. 

Inherent in the reduction of asymmetrically substituted cyclic imides is the problem of regiose-lectivity. Imides, in which one carbonyl group is part of a (thio)carbamate or urea function, usually show complete chemoselectivity for reduction of the other carbonyl group, indicated with an arrow. 

In accordance with this, the reaction of the electron-donor-substituted butadienes 170 (R=Ph, OMe) with the arylcarbene complexes 163 yields divinylcyclopropane intermediates 168 with high chemoselectivity for the electron-rich double bond in 170, which readily undergo a [3,3]-sigmatropic rearrangement to give the as-6,7-disubstituted 1,4-cycloheptadiene derivatives... 

Chemoselective alkynylation in the C-3 position of N-substituted 3,5-dichloropyrazin-2(lH)-one has been described by Van der Fycken et al. [27]. When a mixture of 3,5-dichloro-l-benzylpyrazin-2(lH)-one and pheny-lacetylene in a mixture of NFts and DMF, using Pd(OAc)2/PPh3 as precatalyst and Cul as a co-catalyst, was irradiated for 15 min at 120 °C, the desired l-benzyl-5-chloro-3-phenylethynylpyrazin-2(lH)-one could be isolated with a 77% yield (Scheme 50). Although 2.4 equiv of alkyne were used, no trace of the 1-benzyl-3,5-diphenylethynylpyrazin-2(lH)-one could be detected. 

Analogous results were obtained for enol ether bromination. The reaction of ring-substituted a-methoxy-styrenes (ref. 12) and ethoxyvinylethers (ref. 10), for example, leads to solvent-incorporated products in which only methanol attacks the carbon atom bearing the ether substituent. A nice application of these high regio-and chemoselectivities is found in the synthesis of optically active 2-alkylalkanoic acids (ref. 13). The key step of this asymmetric synthesis is the regioselective and chemoselective bromination of the enol ether 4 in which the chiral inductor is tartaric acid, one of the alcohol functions of which acts as an internal nucleophile (eqn. 2). 

Apart from information on stereochemistry, bromine bridging does not provide a priori any rule regarding regio- and chemoselectivity. Therefore, we systematically investigated (ref. 3) these two selectivities in the bromination of ethylenic compounds substituted by a variety of more or less branched alkyl groups (Scheme 4). 

In another route employing alkynes, it was found that heating propargyl azadienes 7 in toluene at 25-60 °C produces pyrrolic imines 8 which hydrolyze upon work-up to afford 3-acylpyrroles 9 <96JOC2185>. This exo-dig cyclization occurs with complete chemoselectivity wherein the more substituted nitrogen is involved in the cyclization. 

Removing the substituted hydrazine (58) leaves acetoacetic ester (57). Phenylhydrazine is available, so it is easier to make (59) and methylate afterwards. This removes the chemoselectivity problem as the more nucleophilic NH group attacks the more electrophilic ketone. 

The complexes [Cu(NHC)(MeCN)][BF ], NHC = IPr, SIPr, IMes, catalyse the diboration of styrene with (Bcat) in high conversions (5 mol%, THF, rt or reflux). The (BcaO /styrene ratio has also an important effect on chemoselectivity (mono-versus di-substituted borylated species). Use of equimolecular ratios or excess of BCcat) results in the diborylated product, while higher alkene B(cat)j ratios lead selectively to mono-borylated species. Alkynes (phenylacetylene, diphenylacety-lene) are converted selectively (90-95%) to the c/x-di-borylated products under the same conditions. The mechanism of the reaction possibly involves a-bond metathetical reactions, but no oxidative addition at the copper. This mechanistic model was supported by DFT calculations [68]. 

Hydroarylation, (addition of H-Ar, Ar = aryl), of alkynes, catalysed by Pd(OOCCH3)2 or Pd(OOCCFj)j in acetic acid, is an atom-economic reaction, giving rise to substituted c/i-stilbenes (Fujiwara reaction). Catalytic conversions and improved chemoselectivity to the mono-coupled product under mild conditions can be achieved by modification of the metal coordination sphere with NHC ligands. Hydroarylation of mesitylene by ethylpropiolate (Scheme 2.19) catalysed by complex 107 (Fig. 2.18) proceeds in good conversions (80-99%, 1 mol%) under mild conditions at room temperature. 

Surprisingly, the organometallic catalyst shows good stability under the reaction conditions (CFjCOOH/CH Cl ). In the absence of 107 (Fig. 2.18), Pd(OAc)j under the same conditions catalyses the same reaction with reduced activity (ca. 50% conversion in 24 h) and different chemoselectivity. Arenes, substituted by electron-withdrawing snbstitnents react slower. Both internal and terminal alkynes undergo the reaction, however, the former require more forcing conditions [90],... 

As predicted from the comparative rates for C=C over C=C hydrozirconation cited earlier, a (poly)enyne is selectively hydrozirconated at the alkyne moiety, whatever the position of the alkene function [138, 210] in the molecule. It can be exempUfied by the chemoselective hydrozirconation of 1,3-butenyne. One exception to this chemoselectivity has been reported, which showed the terminal alkene to react with 1 but leaving the TMS-substituted alkyne function intact (Scheme 8-25). 

In terms of scope and chemoselectivity, hydrozirconation takes its place between hydroboration and hydroaiumination. However, the synthetic applications of organozirconocene complexes have been considerably expanded over these last few decades, and it can be expected that they will become more and more attractive in the future. Beside the direct substitution sequences, indirect reaction pathways involving transmetalation or activation by ligand abstraction have been successfully applied in a number of cross-coupling and C-C bond-forming reactions. 

Scheme 24) [38]. Chemoselective enolization of the less substituted enone moiety under hydrogenation conditions accompanied by subsequent aldol reaction provided the corresponding hydroxyl-enones, such as 87-89, which could be converted to various building blocks for polypropionate synthesis. p-Me2N styryl vinyl enone also was employed successfully as an enolate precursor, as demonstrated by the formation of hydroxy enone 90. 

The reductive coupling/silylation reaction was extended to more complicated polyenes, such as the triene-substituted cyclopentanol 73, which cyclizes to provide 74 with a 72% yield and 6 1 dr after oxidation (Eq. 10) [44], The reaction is chemoselective the initial insertion occurs into the allyl substituent, which then inserts into the less hindered of the two remaining olefins, leaving the most hindered alkene unreacted. 

The domino reaction is initiated by the chemoselective attack of the carbanion 2-458 on the terminal ring carbon atom of epoxyhomoallyl tosylate 2-459 to give the alkoxides 2-460 after a 1,4-carbon-oxygen shift of the silyl group. The final step to give the cyclopentane derivates 2-461 is a nucleophilic substitution. In some cases, using the TBS group and primary tosylates, oxetanes are formed as byproducts. 

Tandem azidination- and hydroazidination-Hiiisgen [3 +2] cycloadditions of ynamides are regioselective and chemoselective, leading to the synthesis of chiral amide-substituted 1,2,3-triazoles <06OBC2679>. A series of diversely l-substituted-4-amino-l,2,3-triazoles 132 were synthesized by the copper-catalyzed [3+2] cycloaddition between azides 130 and ynamides 131 <06T3837>. 

For the methyl-substituted ethylenes, i.e. in the absence of any steric effects, there is a roughly linear relationship between the chemoselectivity and the 13C nmr chemical shift of the most substituted carbon atom of the bromonium ions (Dubois and Chretien, 1978). This selectivity is therefore discussed in terms of the magnitude of the charge on the carbon atom and the relative hardness of the competing nucleophiles, according to Pearson s theory (Ho, 1977). However, this interpretation does not take into account the substituent dependence of the nucleophilic solvent assistance, which must play a role in determining this chemoselectivity. 

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