Stereospecific reactions cycloaddition

Recall from Section 7.13 that a stereospecific reaction is one in which each stereoisomer of a particular starting material yields a different stereoisomeric form of the reaction product. In the examples shown, the product from Diels-Alder cycloaddition of 1,3-butadiene to c/s-cinnamic acid is a stereoisomer of the product from trans-cinnamic acid. Each product, although chiral, is formed as a racemic mixture. 

Cycloadditions with the Si(lOO) surface were theoretically [133] concluded to be reactions in the pseudoexcitation band. The conclusion is applicable to thermal [2+2] cycloaddition reactions of unsaturated bonds between heavy atoms. In fact, Sekiguchi, Nagase et al. confirmed that a Si triple bond underwent the stereospecific reactions with alkenes [137] along the path typical of [2+2] cycloaddition in the pseudoexcitation band. The stereospecific [2+2] cycloadditions of were designed by Inagaki et al. (Scheme 28) [138]. 

A cycloaddition reaction produces a ring of atoms by forming two new G-bonds, for example the formation of a cyclobutane dimer from two alkene molecules. The direct photoreaction involves the concerted reaction of the singlet Jtpt ) excited state of one alkene with the ground state of the other. Stereospecific reactions in which the dimers preserve the ground-state geometry occur when liquid cis- or trans-but-2-ene are irradiated at low temperature ... 

The formation of five-membered tetrahydrothiophene rings using nonsymme-trical reaction partners usually occurs with high regioselectively. In most cases, a stereospecific reaction was observed (9,27,94). Recently, a diastereoselective cycloaddition of the parent species la to various chiral a,p-unsaturated amides was also reported (32,95). 

This chapter follows on from chapter 12 where we introduced some basic ideas on stereocontrol. Since then we have met many stereospecific reactions such as pericyclic reactions including Diels-Alder (chapter 17), 2 + 2 photochemical cycloadditions (chapter 32), thermal (chapter 33) cycloadditions, and electrocyclic reactions (chapter 35). Then we have seen rearrangements where migration occurs with retention at the migrating group such as the Baeyer-Villiger (chapters 27 and 33), the Amdt-Eistert (chapter 31) and the pinacol (chapter 31). 

The reaction of hexachlorocyclopentadiene with electron-rich alkenes is classified as inverse electron demand Diels-Alder reaction, but its reaction with electron-poor alkenes is considered as a stepwise process based on a lack of stereospecificity. The cycloaddition of 7 with ethyl vinyl ether ... 

The Diels-Alder reaction between (2 ,4Z)-hexa-2,4-diene with the dieno-phile 2-methoxycyclohexa-2,5-diene- 1,4-dione yields four stereoisomers. The Diels-Alder reaction is a stereospecific reaction, therefore the configuration of both the starting materials is relocated in the product. Since the reaction is a concerted [4 + 2] cycloaddition, all the products here have always cis-fused rings and because the configuration of (2 ,4Z)-hexa-2,4-diene remains unaltered, both methyl groups in the product will be trans to each other. The various stereoisomers result because the diene and the dienophile may approach each other from both sides and in two distinct orientations. Note that the reaction occurs almost exclusively at the electron poor double bond of the dienophile. In order to deduce the relationships the... 

Thioaldehyde S-oxides behave as dienophiles with 1,3-dienes [241]. Cycloaddition involves the carbon-sulfur double bond of the heterocumulene to furnish dihydro-2H-thiapyran S-oxides (Table 6, entry 1). The cis trans product ratio was found to depend upon the initial diene/sulfine ratio. A large excess of diene selectively provided the cis cycloadducts, as a result of a stereospecific reaction of the (Z) sulfine. With a produced proportion of diene, mixtures of cis trans isomers are obtained, with a preference for the cis compound. The Italian authors have demonstrated that the slower reaction allows a (Z) to (E) isomerisation of the sulfines prior to addition. 

Otto Diels and his pupil Kurt Alder received the Nobel Prize in 1950 for their discovery and work on the reaction that bears their names. Its great usefulness lies in its high yield and high stereospecificity. A cycloaddition reaction, it involves the 1,4-addition of a conjugated diene in the s-cis-conformation to an alkene in which two new sigma bonds are formed from two pi bonds. 

Cerfontain and coworkers150,325-327 have shown that both sultone and carbyl sulphate formation are stereospecific reactions. Roberts and coworkers324 have indicated that the reaction is a [2 + 2] cycloaddition process however, some earlier workers have argued that the reaction is a step-wise process321,329. 

The high level of stereospecificity in cycloaddition reactions with ketenes points to a concerted mechaitism in which both carbon-carbon bonds are formed simultaneously (although not necessarily at the same rate). Orbital symmetry considerations predict that the thermal [2+2] cycloaddition reaction is disallowed, however. 

The stereochemistry of these cycloadditions is so specific that it may be used as a diagnostic test for the identification of singlet and triplet carbenes. If the reaction is conducted in the presence of triplet quenchers, substances such as butadiene, which selectively remove any triplet carbenes, the addition is again stereospecific. Reactions involving free carbenes are very exothermic because two new a bonds... 

The Rules for the stereospecificity apply only to pericyclic reactions which are concerted. The Rules apply neither to non-concerted reactions nor to those that are not pericyclic. Pericyclic reactions are those which involve a monocyclic transition state having a conjugated array of interacting orbitals, one per atom. Three types of pericyclic processes have been recognized electrocyclic reactions, cycloadditions, and sigmatropic shifts. 

In this chapter, we will see electrocyclic reactions in which rings open and close, cycloaddition reactions in which two partners come together to make a new cyclic compound, and sigmatropic shifts in which one part of a molecule flies about coming to rest at one specific position and no other. Specificity is the hallmark of all these reactions atoms move as if in lock step in one direction or another, or move from one place to one specific new place, but no other. The chemical world struggled mightily to understand these mysteriously stereospecific reactions, and, thanks to the work by Woodward, Hoffmann, and several others, finally figured it out in a marvelously simple way. This chapter will show you some wonderful chemistry. 

Reaction rules (1) Syn-addition principle Diels-Alder reaction is triggered by overlapping dienophile and the p track of n bond in diene. Therefore, Diels-Alder reaction is a stereospecific reaction, and the initial latent chiral center substituent remains unchanged. (2) Endo-addition principle In the cycloaddition reaction, the electron-withdrawing group of dienophile heads to the internal direction of diene. It can be explained by the secondary track overlap, but there are some limitations, so this rule is not suitable for all cases [1, 2]. 

The [2+2] cycloaddition reaction of isocyanates proceeds better with olefins having electron donating groups attached to the double bond system. Examples include vinyl ethers, enamines, ketene acetals, tetraalkoxy- or tetraalkylaminooleflns. The more reactive sulfonyl and carbonyl isocyanates undergo cycloaddition reactions with vinyl ethers especially well. For example, the reaction of vinyl ethers with p-toluenesulfonyl isocyanate affords the [2+2] cycloadducts in a stereospecific reaction... 

Diradicals. Orbital symmetry arguments suggest the [2+2] cycloaddition should not be concerted, and experiments of various types suggest that these reactions do, indeed, involve diradicals (9a,53-55). The arguments are primarily based on the lack of stereospecificity in cycloaddition reactions. However, recently, several reports have been published in which 1,4-diradi-cals have been trapped by added reagents. Table III presents these data. Most of the diradicals are produced photochemically. 

Fluorinated alkenes have been reported to give cyclobutane derivatives by thermal additions to other alkenes. Olefins in their ground electronic states have not been observed to give stereospecific cycloaddition one with another whereas a carbon-carbon double bond which is part of an allene or keten will undergo stereospecific concerted cycloadditions. The separate reactions of tetrafluoroethylene with cis- and trans-[l,2- H2]ethylene, which should not be subject to an adverse steric effect, have been studied to establish whether these reactions are stereospecific. Identical mixtures of products were obtained from both reactions, as expected if they proceed through the... 

A new theoretical description of photolytic [2 -I- 2] cycloadditions includes the suggestion that, as in the case of thermal reactions, biradical mechanisms have too frequently been invoked erroneously to account for ostensibly non-stereospecific reactions. The apparent non-stereospecificity may rather be due to competing concerted reactions, each one of which is differently stereospecific. 

Iron-complexed diene systems have a reduced electron density due to 7t-donation to the iron center. This makes them less reactive towards electrophilic attack that stands for the majority of reactions at olefmic systems. But also oxidation, reduction, and cycloaddition reactions proceed more slowly or can be completely suppressed when the diene is ligated to an iron center. Moreover, the iron complex blocks one face of the diene system. Incoming reagents, whether at the diene unit or at the periphery, are directed anti to the iron complex fragment. This allows stereospecific reactions that are otherwise difficult to achieve. The stereodirecting effect can be exploited for reactions... 

A -l,3,4-Thiadiazolines.—The cycloaddition of aromatic sulphines to nitril imines is a regiospecific non-stereospecific reaction resulting in the formation of A -l,3,4-thiadiazoline derivatives. Interaction of the sulphines (137) and diphenylnitrilimine [generated in situ by the action of triethylamine on N-a-chlorobenzylidene-N -phenylhydrazine (138) in boiling benzene] gave uniform 1 1 adducts that were identified as the A -l,3,4-thiadiazoline S-oxides (139), the alternative 1,2,3-thiadiazoline structure (141) being conclusively eliminated on the basis of chemical and spectroscopic evidence. The non-stereo specific nature of the reaction was demonstrated and its significance discussed. ... 

Carbenes and carbenoids constitute a class of reactive intermediates traditionally intimately associated with the synthesis of cyclopropanes, and more recently with products derived from C-H insertion processes. The reactions of diazoacetic acid esters with aromatic hydrocarbons such as toluene to give cyclopropanes with the liberation of N2, date back to the seminal experiments by Buchner and Curtius reported in 1885 [11]. Much later, in 1942, Meerwein reported that carbenes generated from diazomethane undergo insertion into C-H bonds [12], Seminal experiments that had significant impact for the utilization of such reactions in synthesis were performed by Stork, who demonstrated that carbenes prepared by photolysis of diazoketones participated in stereospecific intramolecular cycloadditions with al-kenes to form bicyclic cyclopropanes (Equations 1 and 2) [13]. Julia reported that intramolecular C-H insertion reactions of a chiral substrate 5 including a stereogenic methine center proceeded stereospecifically with retention of configuration (Equation 3) [14]. 

Ozonation ofAlkenes. The most common ozone reaction involves the cleavage of olefinic carbon—carbon double bonds. Electrophilic attack by ozone on carbon—carbon double bonds is concerted and stereospecific (54). The modified three-step Criegee mechanism involves a 1,3-dipolar cycloaddition of ozone to an olefinic double bond via a transitory TT-complex (3) to form an initial unstable ozonide, a 1,2,3-trioxolane or molozonide (4), where R is hydrogen or alkyl. The molozonide rearranges via a 1,3-cycloreversion to a carbonyl fragment (5) and a peroxidic dipolar ion or zwitterion (6). 

---