Stereochemistry alkene/diene reactions

One application of the reaction shown in equation (52) is the conversion of cyclic, conjugated dienes into exocyclic alkenes. Although the stereochemistry of the reaction needs to be established, the cycliza-tion-protonolysis sequence may provide a convenient route to stereodefined exocyclic alkenes, as suggested by the examples given in equations (53) and (54). These reactions are all at least 90-95% regioselective, as judged by NMR. 

Stereoisomers are now covered (Chapter 4) before the students see any reactions. Therefore, the Reactions of Alkenes (Chapter 6) now covers both the reactions of alkenes and the stereochemistry of those reactions. This reorganization also allows the compounds in Group I (alkenes, alkynes, and dienes) to be covered sequentially. 

It is possible to prepare 1-acetoxy-4-chloro-2-alkenes from conjugated dienes with high selectivity. In the presence of stoichiometric amounts of LiOAc and LiCl, l-acetoxy-4-chloro-2-hutene (358) is obtained from butadiene[307], and cw-l-acetoxy-4-chloro-2-cyclohexene (360) is obtained from 1.3-cyclohexa-diene with 99% selectivity[308]. Neither the 1.4-dichloride nor 1.4-diacetate is formed. Good stereocontrol is also observed with acyclic diene.s[309]. The chloride and acetoxy groups have different reactivities. The Pd-catalyzed selective displacement of the chloride in 358 with diethylamine gives 359 without attacking allylic acetate, and the chloride in 360 is displaced with malonate with retention of the stereochemistry to give 361, while the uncatalyzed reaction affords the inversion product 362. 

The reaction of the allylic acetate with a diene system 784 affords the poly-fused ring system 785 by three repeated alkene insertions[487]. An even more strained molecule of the [5.5.5.5] fenestrane 788 has been constructed by a one-pot reaction in a satisfactory yield by the Pd-catalyzed carbonylation-cycliza-tion of 786 without undergoing elimination of /3-hydrogen in the cr-alkylpalla-dium intermediate 787 owing to unfavorable stereochemistry for syn elimination[488]. 

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

Ketone p-toluenesulphonyl hydrazones can be converted to alkenes on treatment with strong bases such as alkyl lithium or lithium dialkylamides. This reaction is known as the Shapiro reaction68. When w./i-LinsaUi rated ketones are the substrates, the products are dienes. This reaction is generally applied to the generation of dienes in cyclic systems where stereochemistry of the double bond is fixed. A few examples where dienes have been generated by the Shapiro reaction have been gathered in Table 669. 

A normal Diels-Alder reaction is a (n4s + n2s) cycloaddtion and the stereochemistry of both the diene and alkene is retained in the cyclization process. The diene and alkene approach each other in parallel planes. The bonding ineraction involves between Cj and C4 of the diene and carbon atoms of the dienophilic double bond are in a six center arrangement as illustrated below ... 

Wender and co-workers focused their attention on the selectivity of the reaction with dienynes mediated by rhodium catalysts. Disubstituted alkynes give excellent yields of PK products, whereas terminal alkynes react less efficiently. Substituents at 2- and 3-positions in the diene moiety tolerate well. The stereochemistry of alkenes is well conserved during the transformation. ... 

All of the photochemical cycloaddition reactions of the stilbenes are presumed to occur via excited state ir-ir type complexes (excimers, exciplexes, or excited charge-transfer complexes). Both the ground state and excited state complexes of t-1 are more stable than expected on the basis of redox potentials and singlet energy. Exciplex formation helps overcome the entropic problems associated with a bimolecular cycloaddition process and predetermines the adduct stereochemistry. Formation of an excited state complex is a necessary, but not a sufficient condition for cycloaddition. In fact, increased exciplex stability can result in decreased quantum yields for cycloaddition, due to an increased barrier for covalent bond formation (Fig. 2). The cycloaddition reactions of t-1 proceed with complete retention of stilbene and alkene photochemistry, indicative of either a concerted or short-lived singlet biradical mechanism. The observation of acyclic adduct formation in the reactions of It with nonconjugated dienes supports the biradical mechanism. 

An alternative is to put the alkene in another place 84 and discover a different pair of diene 86 and dienophile 85. Again the -isomers will be easier to make and this time we get the right stereochemistry 88 for a-lycorane 71. This strategy was followed in an early synthesis by Hill.9 Another synthesis using the Diels-Alder reaction is by Irie.10 More details appear in the workbook. 

The uncoordinated portion of the 3-vinylpyrrole complexes described above resembles an electron-rich diene, and undergoes a Diels-Alder reaction under mild conditions with electron-deficient alkenes and al-kynes to give functionalized 5,6,7,7a-tetrahydroindole complexes 122 and 149-164 in moderate to excellent yields (Table 10). In most cases, only one stereoisomer is observed even though up to four new stereocenters are formed. For tetrahydroindole complexes 122 and 150, relative stereochemistry has been assigned and is consistent with cycloaddition occurring through an endo-transition state as well as dienophile attack occurring anti to metal coordination. Furthermore, no isomerization occurs to the 4,5,6,7-tetrahydroindole system, which predominates for uncoordinated tetrahydroindoles.23... 

In a similar but more complex reaction, dienes carrying a (3-diketo side chain have been alkylated with various vinyl bromides and cyclized to the corresponding alkylated cyclopropyl alkenes in the presence of silver carbonate (Scheme 10.27). With a relative cis stereochemistry for the newly created C-C bonds, the mechanism is... 

In 1928, German chemists Otto Diels and Kurt Alder discovered that alkenes and The Diels-Alder alkynes with electron-withdrawing groups add to conjugated dienes to form six-ReaCtion membered rings. The Diels-Alder reaction has proven to be a useful synthetic tool, providing one of the best ways to make six-membered rings with diverse functionality and controlled stereochemistry. Diels and Alder were awarded the Nobel Prize in 1950 for their work. 

We now turn to the stereochemistry governed by a ring system, and we shall look at both nucleophilic and electrophilic attack, since usually they have similar stereochemical preferences rather than contrasting preferences. In addition to several reactions that are straightforwardly electrophilic attack, we shall see several which can be described as electrophilic in nature, like the reactions of alkenes with osmium tetroxide, with peracids, with some 1,3-dipoles, and with boranes, and of dienes with dienophiles in Diels-Alder reactions. Some of these reactions are pericyclic, the pericyclic nature of which we shall meet in Chapter 6. For now, it is only their diastereoselectivity that will concern us. 

The confomiational preferences and stereoselective reactions of a number of macrocyclic systems have been studied. The stereochemical results have been explained on the basis of the model of local conformer control. The epoxidation of a macrocyclic alkene containing the substitution pattern (21) provides a single epoxide having the stereochemistry (22). A macrocycle containing a l,S-diene system adepts the local confoimation (23) that is iree of torsional strain epoxidation of (23) from the less hindered side fiimishes the syn-diepoxide (24). The MCPBA epoxidations of the unsaturated macrocyclic lactones (25) and (2Q are stereoselective (equations 9 and 10). In the epoxidation of (26) six new chiral centres are introduced the reaction product is a 20 1 1 mixture of triepoxides. The tiiepoxide (27) is closely related to the C(9)-C(23) segment of monensin B. 

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