Retro reactions

Since a reaction is considered during a retrosynthetic analysis in a direction opposite to its actual course, it is called a retro-reaction or transform (Figure 10.3-30). 

Information-oriented systems are based on a Hbrary of known retro-reactions which have been collected and evaluated by a group of chemists while coding them in electronic form. In addition, information on the scope and the expected yield under various conditions, as well as a strategic merit, is usually stored. 

When hexafluoroacetone reacts with amides, urethanes [25], thioamides [26], amidines [27], sulfonamides [28, 29], sulfinainides [20], and f),0-dialkyl-amido-phosphates [27], the correspondmg semiamidals are formed m nearly quantitative yield The thermal stabihty of these adducts toward the retro reaction increases with the nucleophihcity of the ammo compound [5] Many polyfluonnated carbonyl compounds react likewise [22 22] On treatment of ureas [34], thioureas [34], thioamides [26], and C,77 diarylatmdmes [27, 25] first with hexa- fluoroacetone and then with dehydratmg agents, heterodienes are obtamed (equation 4)... 

The facile, photoinduced valence isomerization of ethyl 1//-azepine-l-carboxylate to ethyl 2-azabicyclo[3.2.0]hepta-3,6-diene-2-carboxylatehas been studied as a potential solar energy storage system.101102 Unfortunately, the system proved to be inefficient due to build up of polymeric material during the thermally induced, exothermic retro-reaction. 

It is interesting to note that no examples are known for a retro-reaction of this dimerization. Such a reaction has been observed, however, for germylene complexes and for stannylene complexes, in some cases an equilibrium between uncomplexed and base-stabilized compounds has been found. 

If the product has a more highly substituted double bond than the substrate, the retro-reaction is kinetically hindered because most catalysts are sensitive to the substitution pattern of the olefin (cf. Sect 3.1). 

For 2.22 C-e the following retro reactions can be envisaged leading to new products see Figure 2.23. 

Hydrocyanation of butadiene is more complicated than that of ethene it requires two hydrocyanation steps and several isomers can be observed. The isomers obtained in the first step of the HCN addition to butadiene are shown in Figure 11.3. The addition first leads to compounds 1 and 2, in a 1 2 ratio, but they equilibrate to a favourable 1 9 ratio via the retro-reaction. The retro reaction involves a C-C bond breaking reaction, which is rare, but in this case the intermediate is a Tt-allyl species and a stable, anionic cyanide group. Electron-rich nickel species (Ni-dippe) can cleave aromatic nitrile C-C bonds... 

Giue a name to disconnection (retro-reaction) Name... 

Cyclopentadiene adducts (mono-, tetra- and hexa-adducts) of were stabilized against retro-reaction by selective hydrogenation and bromination of the pendant groups [21]. Utilization of Adam s catalyst and dilute bromine solutions exclusively leads to an addition to the cyclopentene double bonds, because itself is inert towards these reagents. The increased stability of the reduced cycloadducts can be demonstrated by mass spectrometry [21]. 

THF and hexane can be removed under reduced pressure using a rotary evaporator. The chance of the retro-reaction (to R CsCLi and R r3c=0) is very small if the bath temperature is kept below 45 G The remaining viscous solution is cooled to 0 C and,a cold aqueous solution of NH4O is added. By reducing the amount of THF and hexane, losses of product during the removal of solvent after aqueous work up are minimized. The procedure seems risky when Ri = CjH O or MejSi. 

Azepines, prepared by base-promoted ring expansion of dihydropyridines, undergo a retro-reaction on treatment with HC1 or HBr (see Scheme 37 Section 5.16.4.2.3). In contrast, 4H-azepine (87) isomerizes in CHCl3-dilute hydrochloric acid or CHCI3-TFA to the 1//-azepine (71JCS(C)1237). 

Interestingly, a second allenyl adduct, isomeric with the major product, was also formed in the latter reaction. This isomer was surmised to arise by a retro reaction of the initial allenyl adduct to form a TMS propargylzinc bromide reagent, which subsequently adds to the liberated aldehyde (equation 12). The regiochemistry of this addition is also thought to be directed by steric effects, again involving the methyl and TMS substituents. 

The [,4 + 2] cycloaddition of dienophiles with 1-substituted pyrroles is also a reversible reaction, which has been utilized in the synthesis of 3,4-disubstituted pyrroles (b-77MI305oq) and, via the initial reaction of the pyrrole with benzyne, for the synthesis of isoindoles (81 AHC(29>341). The retro-reaction can be controlled and aided by a 1,3-dipolar cycloaddition of the intermediate adduct with benzonitrile oxide (74TL2163, 76RTC67) (Scheme 61). 

The thermal retro-reaction of 3-sulfolenes to dienes and sulfur dioxide occurs under mild conditions (about 120-200°C), and is, as predicted from the Woodward-Hoffmann rules, a disrotatory process so for 2,5-dimethyl-3-sulfolenes [541,542] ... 

The first step of the retro-reaction involves loss of silylene 79, which could be trapped with 1-pentyne to give the known silirene 81 (equation 125). In the absence of a trapping agent, 79 recondenses to 77, probably by first dimerizing to the disilene Ar2Si=SiAr2 followed by 2 +1 cycloaddition to give 77 (equation 126). From the principle of microscopic reversibility, the fact that silylene is formed in the retro-reaction leads to the conclusion that 79 must also be an intermediate in the cycloaddition reaction. 

The reactions of transient silylenes are so rapid that most of the limited mechanistic information that has been obtained over the past quarter-century has been through indirect means. Direct measurements of silylene reaction rates by kinetic spectroscopy in the past decade have yielded important new insights. One can predict with some confidence an explosion of mechanistic studies of silylenes employing fast spectroscopies capable of providing more structural information than traditional electronic absorption and emission techniques. The nearly universal reversibility of silylene reactions remains to be fully exploited through kinetic studies of retro-reactions. The mechanisms of most silylene reactions remain to be fully elucidated, and this task will increase in urgency as silylenes see more use in synthesis. 

In some cases it is the diene component from the retro reaction which is the desired product and extrusion of a volatile alkene such as ethylene is then ideal. Pyrolysis of the 1,4-oxathiin systems 21 proceeds in this way to give the a-oxothiones 22 which for R = Pr1, exists mainly as the enethiol tautomer 2323. Thermal extrusion of ethylene from 24 provides convenient access to the interesting fulvene 25 in quantitative yield24, and the corresponding reaction of 26 at 650 °C and 10-4 torr gives the cyclopentadienoben-zopyrene 28 in 95% yield, presumably by way of the intermediate 2725. 

This intramolecular reaction results in the formation of a cyclic system, and therefore it is called ring-closing metathesis (RCM). In this process a diene 36 is treated with a metal alkylidene 37. Two competing pathways are available via the intermediate metal alkylidene 38 A) RCM will occur to afford cyclic adducts 39 and B) intermolecular reaction can occur to form polymeric structures 40 (acyclic diene metathesis polymerization (ADMET)). The reaction is also complicated because of the possibility of ring-opening metathesis (ROM), the retro reaction of path A, and ring opening metathesis polymerization (ROMP) (path C).13... 

Because an equilibrium constant is not affected by catalysis, an enzyme that accelerates a forward reaction must also accelerate the reverse or retro-reaction. Furthermore, the enantioselectivity for both reactions will be identical. Antibody 38C2 catalyzes both the forward and retro-aldol reaction, and we envisioned that it may be useful in the kinetic resolution of aldols. Because the product enantiomer from the forward aldol reaction is the substrate in the retro-aldol reaction, the opposite... 

A retro-aldol reaction (s just an aldol reaction in the reverse direction, You will meet ether retro reactions later in the book, such as the Important retro-Dlels-Aider reaction In Chapter 35. 

A disadvantage of traditional DielsAlder methodology is the ease with which the retro-reaction occurs in some cases, particularly when the reactions have to be conducted at high temperatures. The transition state in the DielsAlder... 

These reaction products (or more precisely products of the retro-reaction) were obtained by applying a formal scheme. In relocating the bonds no information on the specific reaction at hand was needed. In generating the reaction products it was... 

Applying the general reaction schemes contained in our program system onto the bonds of molecules allows the generation of all conceivable reactions or retro-reactions of these molecules. The task is then to select the chemically feasible reactions from the set of the mathematically possible ones. Here lie the main efforts in... 

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