Prototropic isomerizations

Unsaturated substituents of dioxolanes 36-38 and dioxanes 39-41 are prone to prototropic isomerization under the reaction conditions. According to IR spectroscopy, the isomer ratio in the reaction mixture depends on the temperature and duration of the experiment. However, in all cases, isomers with terminal acetylenic (36, 39) or allenic (37, 40) groups prevail. An attempt to displace the equilibrium toward the formation of disubstituted acetylene 41 by carrying out the reaction at a higher temperature (140°C) was unsuccessful From the reaction mixture, the diacetal of acetoacetaldehyde 42, formed via addition of propane-1,3-diol to unsaturated substituents of 1,3-dioxanes 39-41, was isolated (74ZOR953). 

Allyl p-tolyl sulphoxide 535 reacts with sodium methoxide in methanol by initial prototropic isomerization and subsequent addition of methanol to give 536 (equation 333). Protic solvents are photochemically incorporated by the open chain olefinic bond of trans methyl )S-styryl sulphoxide 537 in a Markovnikov regiospecificity (equation 334). Mercaptanes and thiophenols add to vinyl sulphoxides in a similar manner (compare also Reference 604 and Section IV.B.3) to give fi-alkylthio(arylthio)ethyl sulphoxides 538 (equation 335). Addition of deuteriated thio-phenol (PhSD) to optically active p-tolyl vinyl sulphoxide is accompanied by a low asymmetric a-induction not exceeding 10% (equation 336) . Addition of amines to vinyl sulphoxides proceeds in the same way giving )S-aminoethyl sulphoxides in good to quantitative yields depending on the substituents at the vinyl moiety When optically active p-tolyl vinyl sulphoxides are used in this reaction, diastereoisomeric mixtures are always formed and asymmetric induction at the p- and a-carbon atoms is 80 20 (R = H, R = Me) and 1.8 1 (R = Me, R = H), respectively (equation 337) ... 

The isomerization of the smallest alkynes 80 with halogens in a propargylic position has been described for chlorine [151, 152], bromine [153] and iodine [154] (Scheme 1.35), but often might proceed by an SN2 -type substitution rather than a prototropic rearrangement [155-159]. On the other hand, transformations such as 82 —> 83 [160] or 84 —> 85 [161] are clearly prototropic (Scheme 1.36). This is also true for propargylic halides such as 86 with its additional ester group assisting the prototropic isomerization [162,163] (Scheme 1.37). 

The combination of a silyl-migration from carbon to oxygen and a prototropic isomerization leads to allenyl silyl ethers [246]. 

Allenes from Prototropic Isomerizations of Alkynes as Reactive Intermediates... 

After the prototropic isomerizations, these rearrangements are the second most important synthetic methodology. In the concerted reactions a highly selective central to axial chirality transfer is possible, but this has already been exploited before the timeframe covered by this review and has been summarized [378]. 

There is not just one predominating method for the generation of alienes with at least one electron-withdrawing group, but a number of important routes. Even for the synthesis of alienes with a given acceptor function, for example allenic esters, different routes are often used such as the Wittig reaction, prototropic isomerization or alkoxycarbonylation. 

In the case of carboxylic acids [33], ketones [47] or sulfones [49], it was possible to prove a further prototropic rearrangement of allenes 19 with R2 = H yielding the alkynes 20. In other examples, the prototropic isomerization of the triple bond leads to conjugated dienes directly thus the allene of type 19 could only be postulated as an intermediate [50]. Braverman et al. showed that the allenes generated by prototropic isomerization of dipropargylic sulfones or sulfoxides, for example 24, are unstable. They are transferred rapidly via diradical intermediates to polycycles such as 27 [51-53],... 

Quaternary allenylallylammonium salts, produced in situ by prototropic isomerization of propargyl precursors (see Section 7.2.2), can undergo a 3-aza-Cope rearrangement [370]. The resulting intermediates are hydrolyzed under the reaction conditions to yield 2 -methylenepent-4-enals. 

Acceptor-substituted allenes can be prepared from the corresponding propargyl precursors by prototropic isomerization (see Section 7.2.2). Conversely, such allenes can also be used to synthesize propargyl compounds. For example, treatment of the sulfoxides 417 with 1 equivalent of a lithiation reagent leads to the intermediates 418, which furnish propargyl sulfoxides 419 by hydrolysis (Scheme 7.55) [101]. If the electrophiles used are not protons but primary alkyl halides or carbonyl compounds, the products 420 or 421, respectively, are formed by C,C linkage. 

One very unusual case of prototropic isomerization was revealed for anion-radicals of 1,4-dihydropyridine derivatives (Gavars et al. 1999). These anion-radicals transform into 4,5-dihydro-pyridine analogs through proton detachment and addition. 

The one-stage transformation of 3-butenyl-l-methyl ketoxime (63) to 2-methyl-3-(2-propenyl-l)pyrrole (64) and 2-methyl-3-(l-propenyl-l)-l-vinylpyrrole (65) (Scheme 34) (82TL5063) is typical and demonstrates two essential features of this version of the reaction the reaction either can be stopped selectively at the stage of pyrrole ring formation without vi-nylation onto the N—H bond and prototropic isomerization of the alkenyl, or it can form an N-vinylpyrrole in which the double bond of the alkenyl is shifted into conjugation with the pyrrole ring. 

The need for the heterocyclization of 0-vinyloximes to pyrroles to be carried out in a superbase medium arises from the fact that a [3,3]sigma-tropic rearrangement should be preceeded by base-catalyzed prototropic isomerization of 0-vinyloxime to the 0,/V-divinylhydroxylamine (cf. Scheme 43, 87,90) (84KGS1077). 

Prototropic isomerization of the propene molecule in the presence of hydroxide ion has been studied using ab initio and DFT methods in the gas phase and in DMSO solution 152 the mechanism involves formation of an intermediate complex of the allyl anion with a water molecule. 

Many more dehydrohalogenations are, however, being carried out in aqueous or alcoholic solution under reflux. Under these conditions the reaction is particularly suitable for the preparation of acetylenes which will not prototropically isomerize, such as arylacetylenes. The following examples illustrate the large number of structural types which can be converted to acetylenes while surviving the strong reaction conditions (equations 9, 29-35). A facile conversion of aryl ketones and... 

Since then major improvements have taken place in the technology front particularly in China and India where this drug is still very popular. For instance, considerable work has been carried out by the Department of Energy Utilization and Chemical Engineering, China University of Mining and Technology. They have reported that efficient synthesis of trimethoprim from 3,4,5-TMBA was accomplished by condensation with methanolic sodium methoxide, methanol and acrylonitrile via prior base-catalyzed 1,3-prototropic isomerization of cinnamonitrile converted into the enol ether, followed by addition with methanol at 90°C and cyclocondensation directly with guanidine in DMSO at 110°C with the removal of methanol. 

The addition of diazoacetic ester to phosphinylallenes gives phosphinylpyraz-oles. Hydroxylamine adds to vinylphosphonates, and the products (96) rearrange under acid conditions. Alkyl diallylphosphinates undergo prototropic isomerization when treated with t-butoxide ion. ... 

The prototropic isomerization of allenylphosphonate into 1-propynylphosphonate proceeds partially or completely under the influence of an organic base that is generally present in the reaction mixture in a catalytic amount.When pure dialkyl allenylphosphonates are heated to 2()0°C, they remain unchanged (apart from partial polymerization). In the presence of basic catalysts (EtONa, 03 NaOlI, and at room temperature or Et3N 5 and triethyl phosphite at... 

The presence of two hydrogen atoms at the nitrogen in the amines permits subsequent prototropic isomerization with the formation of ketenimines. By way of contrast, reactions with primary phosphines lead to halogen-substitution products with retention of the bond and P-H bonds. The reaction of ketenimines with water in the presence of a catalytic amount of HCl proceeds smoothly and leads to a high yield of the corresponding amide. 

Sodium enolates of diethyl 2-oxoalkylphosphonates react with diethyl chlorophosphate to produce enol phosphates. Low-temperature treatment of enol phosphates with tert-BuOK induces the ()-elimination of potassium diethyl phosphate and formation of diethyl 1-alkynylphosphonates in good yields (43-95%, Scheme 7.113). However, the reaction is prone to prototropic isomerization and diethyl 2-oxobutyIphosphonate leads to a mixture of diethyl 1-butynyIphosphonate (43%) and diethyl 2-butynylphosphonate (51%). ... 

Some features of the prototropic isomerization of (1-alkenyl)phosphonic acids and their derivatives have been investigated for basic conditions. By using (halogenoalkenyl)-phosphonic esters, together with CD OD + CD O , it was shown that the speed of isomerization of (1-alkenyi)phosphonic acid derivatives e.g., (308), to the 2-alkenyl)phosphonic isomers, here (309), was faster than H/D exchange at position 3 isotope exchange occurs at position 1 in (309). The 1-alkenyl structure... 

By analogy with the discussion in Sec. III.2 the mechanism of base-catalyzed prototropic isomerization will be... 

When treated with potassium tcrt-butoxide, the [l-(prop-2-ynyl)alkyl]phosphonic diesters 370 (R = H, Me, Ph, etc.) undergo prototropic isomerization to the (1-R-buta-l, 3-dienyl)phosphonic diesters (371). ... 

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