In situ isomerization

Although the path (a), which is the initiation stage of the catalytic reaction, was actually confirmed by a stoichiometric reaction, no direct evidence has been provided about paths (b)-(d). When the reaction was carried out by using PdCl2(PhCN)2 as a catalyst precursor, the Markovnikov adducts formed in situ isomerized into internal vinyl sulfide 14 (Eq. 7.10) [22]. 

A one-pot three-step conversion of aryl fluorides to phenols based on a consecutive nucleophilic aromatic substitution/isomerization/hydrolysis sequence has been reported by Levin and Du (Scheme 6.126) [256], The authors discovered that 2-butyn-l-ol can function as a hydroxyl synthon through consecutive SNAr displacement, in situ isomerization to the allenyl ether, and subsequent hydrolysis, to afford phenols rapidly and in good yields. In most cases, excesses of 2-butyn-l-ol (1-2 equivalents) and potassium tert-butoxidc (2-4 equivalents) were required in order to achieve optimum yields. 

When alkynyl ketones are synthesized, occasionally an in situ isomerization to the allene was reported, for example in the propargylic ether 66 [126] (Scheme 1.29). 

Silyl esters have also been transformed successfully [137] another example reports the O-acylation of serine with a /l-alkynyl carboxylic acid anhydride accompanied by an in situ isomerization of the alkyne to the allene [138],... 

Indole and acetal 372 gave the carbazole 373 in 50% yield in acetic acid. ° It seems likely that conjugated ketone formed in situ isomerizes in two steps to the species 374 that initiates ring formation by attack at the indole -position. 

It has been reported that treatment of methyl 1-methylsulfanylvinyl sulfoxides with sodium thiophenolate in methanol affords l-methylsulfanylalk-l-en-3-ols. A sequence has been proposed218 (see Scheme 45) in which the thiophilic base first causes an in situ isomerization of the vinyl sulfoxide moiety into an allylic sulfoxide which then undergoes a [2,3]-sigmatropic rearrangement and subsequent thiophilic cleavage of the intermediate sulfenic ester. 

A nonclassical substrate for the Heck reaction is 2,3-epoxycyclohexanone. The reactivity of this molecule under Heck coupling conditions is most likely attributed to its in situ isomerization to 1,2-cyclohexanedione. The 1,2-diketone subsequently reacts with aryl bromides as an olefin via the enol tautomer. Thus, within 5 to 30 min of directed microwave heating of the aqueous PEG mixture, up to 13 different C3-arylations were conducted using less than 0.05 mol % palladium acetate and no phosphine ligand (Scheme 12) [51]. 

In asymmetric hydrocyanation reactions the desired isomers are the chiral branched products only. Good regioselectivity toward the branched product (>98%) is limited to vinylarenes. Hydrocyanation of 1,3-dienes gives a variety of mixtures depending on the catalyst and conditions 1-alkenes give the linear nitrile as major product [34]. Both are seen in the adiponitrile process in which the unwanted branched 2M3BN (hydrocyanation product from 1,3-butadiene) is isomerized to the linear product 3-pentenenitrile, which is then hydrocyanated by in-situ isomerization to 4-pentenenitrile, resulting in the linear adiponitrile. Thus vinylarenes and cyclic alkenes (mainly norbomene) are usually the substrates of choice for the asymmetric hydrocyanation. Hopefully 1,3-dienes will become feasible substrates in the near future. 

Intramolecular allylsilylation of alkynes is a convenient route to cyclic vinylsilanes.211 Propargylsilanes are available for Lewis acid-promoted carbosilylation of alkynes.212 Unlike allylsilanes, both cr-substituted and unsubstituted propargylsilanes react at the a-position, which can be rationalized by in situ isomerization of these reagents to allenylsilanes (Equation (55)). 

Addition of the l-benzyl-2-lithiomethyl-4,5-dihydroimidazole 705 to aldehydes or ketones, and the subsequent retro-ene reaction to revert back to the starting material, was discussed in (Scheme 171). The reaction of 705 with nitriles results in the formation of )3-amino ot,)3-unsaturated imidazoline 706 after in situ isomerization <1999T2695>. 

In the second step, the concentration of pyridine as ligand must be low because it has an inhibitory effect on the hydroalkoxycarbonylation. In situ isomerization to the 4-pentenoic acid ester is a prerequisite for the subsequent carbonylation which provides dimethyl adipate. To ensure internal double-bond rearrangement, the temperature of the reaction is increased to 160-200 °C to give dimethyl adipate with 80 % selectivity. After hydrolysis of the ester, adipic acid is obtained with an overall selectivity of about 70% [1]. So far, this process has been performed on pilot-plant scale. 

In another approach, the dehydration has been conducted in ionic liquids (l-alkyl-3-methylimidazolium chloride) under acid or metal chloride catalysis yielding HMF up to more than 80% nearly without any formation of by-products like levulinic acid [32], When using chromium(II) chloride as catalyst even D-glucose could be used as feedstock since this catalyst is effective for the in situ isomerization of o-glucose to o-fructose before dehydration takes place to produce HMF in 70% yield. The catalyst system N-heterocyclic carbene/CrCU in l-butyl-3-methyl imidazolium chloride has been developed for the selective conversion of D-fructose (96% yield) and o-glucose (81% yield) [33]. 

Gabriele and coworkers [36] showed that, besides lactones, furans could also be prepared by a similar process starting from different substrates. Here, a variety of (Z)-2-en-4-yn-l-ols have been carbonylated under oxidative conditions to give substituted furan-2-acetic esters in good yields (Scheme 1.15a). The cycliza-tion/alkoxycarbonylation sequence was carried out in alcoholic media at 50-70 °C under 100 bar pressure of a 9 1 mixture of CO and air. As catalyst system, Pdl2 in combination with KI was used. The proposed reaction pathway involves the in situ isomerization of the initially formed ( )-2-[(alkoxycarbonyl)methylene]-2,5-dihydrofuran species, which in some cases have been isolated and proved to be the intermediates. Under similar reaction conditions, 3-yne-l,2-diols were transformed into the corresponding furan-3-carboxylic esters in good yield (Scheme 1.15b). 

Employing DBU (diazabicycloundec-7-ene), instead, required a much longer reaction time and did not effect the required in situ isomerization of the undesired diastere-omer, which allows cychzation onto the dione from the less hindered face. 

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