Base catalyzed isomerizations

The most active heterogeneous catalysts that are effective at room temperature are alkali metals supported on activated alumina. Simple C4-Cg alkenes, for example, were shown to yield equilibrium mixtures in short contact time over sodium on alumina.112116 Partial conversion of 1-butene at low temperature and in very short contact time (—60°C, 14 s) led to the stereoselective formation of m-2-butene.112 The changes in isomeric composition in the transformation of 4-methyl-l-pentene112 are as follows  

Of the various homogeneous systems, metals and amides in amine solvents and alk-oxides in aprotic solvents are the most active catalysts. Solvents have a profound 

Cycloalkenes may undergo facile double-bond migration117 catalyzed by both homogeneous and heterogeneous catalysts [Eq. (4.21)] establishing equilibrium compositions  

Since alkenylarenes are more acidic than simple alkenes, they are more reactive to yield isomers with the double bond in conjugation with the aromatic ring 120 

Most studies concerning the mechanism of base-catalyzed alkene isomerization were conducted with alkenylarenes.121 

---

Dioxopiperazines have been converted into the corresponding dihydroxypyrazines by base catalyzed isomerization of the corresponding arylidene derivatives (Scheme 64) (70JCS(C)980), although this reaction appears to be limited to the synthesis of benzyl- or aryl-substituted benzylpyrazines. 

Although there is very little scope for reactions of the above types with 1,2-benzisoxazole derivatives, the quaternary salts such as 2-methyl-3-phenyl-l,2-benzisoxazolium salt underwent base-catalyzed isomerization to the 1,3-benzoxazine shown in Scheme 83. This reaction is analogous to the formation of (202) above (67AHC(8)277). 

Extension of the above method to 3-methoxyestra-3,5(10)-dien-17-one 17-ethylene ketal (46) prepared by base-catalyzed isomerization of 3-methoxy-estra-2,5(10)-dien-17-one 17-ketal (42) with potassium t-butoxide in dimethyl sulfoxide gives the isomeric tropone A-homo-estra-l,4,5(10)-triene-3,17-dione... 

The base-catalyzed isomerization of N,N-dialkylallylamines (179) to a mixture of enamines consisting primarily of the cis isomer (180) has been reported 128). The assignments were based upon the magnitude of the... 

An interesting consequence of the base-catalyzed isomerization of unsatu-rated ketones described in Problem 22.37 is that 2-substituted 2-cyclopen tenones can be interconverted with 5-sub tituted 2-cyclopentenones. Propose a mechanism for this isomerization. 

Treatment of the minor product formed in the intramolecular aldol cyclization of 2,5-heptanedione (Problems 23.30 and 23.31) with aqueous NaOH converts it into the major product. Propose a mechanism to account for this base-catalyzed isomerization. 

A final, rather different example which fits in appropriately here, in that it involves hydrogen exchange, is the measurement of equilibrium and rate constants for the base-catalyzed isomerization of unsaturated sulfides, sulfoxides and sulfones193 ... 

A new method has been developed for the synthesis of ( )-3-methyl Baylis-Hillman-type adducts with high E/Z (>93%) selectivity in modest to good yields. The process consists of two steps an indium-mediated allylation reaction and a simple base-catalyzed isomerization step (Eq. 8.61). Various aldehydes were allylated with allyl bromides using indium under very mild conditions in aqueous media and thus converted to the Baylis-Hillman-type adducts.150... 

Cfs-butene should lead initially to the anti form trrms-butene should lead initially to the syn form and 1-butene should give rise initially to both. The equilibrium distribution of syn and anti forms usually differs greatly from the equilibrium distribution of cis- and frans-butene for cobalt complexes 59, 60) the syn form, precursor of irans-butene, is by far the most stable. By way of contrast for the corresponding carbanion, the cis anion seems by far the more stable. This preference for the cis carbanion is presumed to be the source of the high initial cis-to-trans ratio in the initial products of base catalyzed isomerization. In the base catalyzed isomerization of more complex cf-s-olefins (cfs-S-methyl-stilbene), the ions corresponding to syn and anti are not interconvertible and cis-trans isomeriza-... 

Extrapolation of the rate data in Fig. 24 to zero conversion shows that the initial ratio of butene-1 to frans-butene formation is about unity. Thus, butene-1 is not an intermediate in the cis-trans isomerization and direct cis-trans isomerization occurs. Similar results are found for the heterogeneous base catalyzed isomerization over sodium on alumina (17). 

This ion plays the role in base catalyzed reactions of acetylenes that allyl carbonions play in base catalyzed reactions of olefins. For a base catalyzed isomerization of methyl acetylene the following is consistent with the accepted pathways ... 

Base-catalyzed Isomerization of Allylic Aromatic Compounds [68]... 

In the present case, the proportion of A2-isomer in the original dehydration mixture may be estimated to be 42% of the total unsaturated esters, while an equilibrium mixture contains about 67% of the conjugated compound.3 Thus, the amount of conjugated isomer in the mixture may be considerably increased by base-catalyzed isomerization of the unsaturated esters. For other unsaturated esters, both the composition of the dehydration mixture3 7 and the equilibrium ratio of tile two isomers 3 x vary, depending on the position and... 

The experimental probe of the conformational preferences of allyl anions is based primarily on the kinetics of base catalyzed isomerization reactions of olefins and many results have been summarized by Bank180). Kinetic data of base catalyzed isomerization of 1-butene181) show that the less stable cis isomer of 2-butene is formed through a thermodynamically more stable allylic anion ... 

Additional evidence for the greater stability of the cis conformation of allylic anions is provided by other base catalyzed isomerization studies of 1-butene and 1-pentene. It was found that the thermodynamically less stable cis isomers of 2-butene and 2-pentene were the major products of the reaction182-186). Furthermore, m-2-butene isomerizes, under the same conditions, faster than the tram isomer to give 1-butene. 

As mentioned in the Introduction, this chapter focuses on reactions that deliver allenes as the product. The principles discussed in Sections 1.2.1-1.2.9, of course, also allow the synthesis of allenes as reactive intermediates, which due to other functional groups that are present, undergo further reactions in situ. The most important examples here are base-catalyzed isomerizations to furans [347, 348] ring transfer reactions of propargylic ethers or amines [216, 349-371] and enyneallene cycliza-tion reactions starting from propargylic sulfones [372-375] and related substrates [376, 377]. Details are discussed, for example, in Chapters 16 and 20. 

Another recent example is the formation of 152 [504] (Scheme 1.68). However, the allene unit was formed by a base-catalyzed isomerization after the [2,3]-Wittig rearrangement of 151. Only one diastereomer was detected the configuration of the allenic unit in 152 was not determined. 

Ethynylallenes [35], the didehydro analogs of vinylallenes, have also been known for some time, the parent system 7 having been obtained in 1960 by reduction of 3-chloro-l,4-pentadiyne (101) with zinc-copper couple in butanol [36] and the 5-methyl derivative 103 by base-catalyzed isomerization of 1,4-hexadiyne (102) with sodium ethoxide in ethanol (Scheme 5.13) [9]. 

Heptatetraene (diallenylmethane) (30) is produced in 1% yield in the base-catalyzed isomerization of 1,6-heptadiyne (243 see below). Its preparation from the bisdibromocarbene adduct 238 to 1,4-pentadiene (237) failed rather than 30, its isomerization product 239, a derivative of 12, was isolated [95] in poor yield and was accompanied by 1- and 6-methylfulvene, respectively [96]. 

The dienyne 33 is produced by base-catalyzed isomerization of 1,6-heptadiyne (243) [98] in a mixture with other C7Hg hydrocarbons, among them traces of dialle-nylmethane (30). The still higher homolog 1,2,7,8-nonatetraene has also been described [99]. 

Dehydrobromination of 219 with DBU gave rise to allyl propargyl ethers 220, which underwent a base-catalyzed isomerization-[4 +2]-cycloaddition sequence to afford tricyclic enol ethers 221 [179]. 

Investigations of base-catalyzed isomerizations of allene derivatives have been recently continued. For instance, the rearrangement of allene ethers 53 under superbasic conditions (KOH-DMSO) is considered as one of the steps in hydration of acetylene derivatives (equation 17)31,32. 

The substantial amounts of this ketohexose are mainly prepared by base-catalyzed isomerization of starch-derived glucose, yet may also are generated by hydrolysis of inulin, a fructooligosaccharide. An aqueous solution of fructose—consisting of a mixture of all four cyclic tautomers (Figure 2.5), of which only the (3-D-pyranose ((3-p) form present to about 73% at room temperature is sweet — about 1.5 times sweeter than an equimolar solution of sucrose hence, it is widely used as a sweetener for beverages ( high fructose syrup ). 

Not only can acids catalyze olefin isomerization, but strong bases can also effect isomerization. These base-catalyzed isomerizations proceed through proton abstraction of an allylic hydrogen atom followed by protonation of the allylic anion to regenerate either the original or the isomeric olefin ... 

In the present chapter, no explicit discussion or review of the acid-and/or base-catalyzed isomerization of olefins will be included. The discussion will be confined to isomerizations achieved with soluble transition metal complexes. However, it will be seen that addition and elimination reactions and allylic intermediates figure prominently in discussions of the mechanisms. 

The cyclizations of /3-hydroxycarboxamides with aldehydes, ketones, or their equivalents results in l,3-oxazin-4-one derivatives <1996CPB734, 2006BMC584, 2006BMC1978>. In the acid-catalyzed condensation of salicylamide 422 with (—)-menthone, a 2 1 mixture of C-2-epimeric 27/-l,3-benzoxazin-4(37r)-ones 202 and 423 was formed, the equilibrium of which could be shifted toward the (23 )-enantiomer 202 by base-catalyzed isomerization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in A -methyl-2-pyrrolidone (NMP) to yield a 14 1 mixture of 202 and 423 (Equation 44) <1996TL3129>. 

The optically active, axially chiral 5-alkylidene-2-aryl-l,3-dioxanes, discussed in Section 8.11.6.4.6, were submitted to a Negishi coupling followed by a base-catalyzed isomerization of the double bond. Both reactions proceed with complete retention of the configuration, allowing the preparation of the chiral 1,3-dioxin with no loss of enantiomeric purity (Scheme 87) <1998TA1657>. 

In conclusion, each of the three synthetic approaches to 256 has its advantages and disadvantages. Base-catalyzed isomerization of epoxides is certainly the simplest method however, it is not applicable in all cases. The use of a specific Base, not prone to side reactions, would be the best approach to the synthesis. 

Another useful method involves the base-catalyzed isomerization of tertiary allylamines to cis- and rranj-propenylamines (Eq. 5). 

Babler and Schlidt [86] described a route to a versatile C15 phosphonate, used for a stereoselective synthesis of all E retinoic acid and p-carotene. Base-catalyzed isomerization of the vinyl-phosphonate afforded the corresponding allyl-phosphonate as the sole product. Homer-Emmons olefination with ethyl 3-methyl-4-oxo-2-butenoate concluded the facile synthesis of all E ethyl retinoate. The C15 phosphonate was synthesized starting from the epoxide of P-ionone. Subsequent isomerization with MgBr2, afforded the C14 aldehyde in 93%... 

Different catalysts bring about different types of isomerization of hydrocarbons. Acids are the best known and most important catalysts bringing about isomerization through a carbocationic process. Brpnsted and Lewis acids, acidic solids, and superacids are used in different applications. Base-catalyzed isomerizations of hydrocarbons are less frequent, with mainly alkenes undergoing such transformations. Acetylenes and allenes are also interconverted in base-catalyzed reactions. Metals with dehydrogenating-hydrogenating activity usually supported on oxides are also used to bring about isomerizations. Zeolites with shape-selective characteristics... 

---