Stereospecific formation

A widely exploited procedure for bringing about carbenoid reactions of organic mono- and fifem-dihalides is by use of lithium alkyls. Examples are given in equations (11) and (12). Dimeric olefin formation, stereospecific cyclopropane formation from olefins, and insertion into carbon-hydrogen bonds have all been observed in suitable cases, together with further reactions of these products with excess of the lithium alkyl. 

Bridges, formation, stereospecific 23, 276 S-Bridges 22, 607, 622 23, 601 Si-Bridges, elimination 21, 970 Bromide ion 21, 879 Bromides s. Halides, Replacement... 

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Electron-deficient alkenes add stereospecifically to 4-hydroxy-THISs with formation of endo-cycloadducts. Only with methylvinyl-ketone considerable amounts of the exo isomer are produced (Scheme 8) (16). The adducts (6) may extrude hydrogen sulfide on heating with methoxide producing 2-pyridones. The base is unnecessary with fumaronitrile adducts. The alternative elimination of isocyanate Or sulfur may be controlled using 7 as the dipolarenOphile. The cycloaddition produces two products, 8a (R = H, R = COOMe) and 8b (R = COOMe, R =H) (Scheme 9) (17). Pyrolysis of 8b leads to extrusion of furan and isocyanate to give a thiophene. The alternative S-elimi-nation can be effected by oxidation of the adduct and subsequent pyrolysis. 

Overall the stereospecificity of this method is the same as that observed m per oxy acid oxidation of alkenes Substituents that are cis to each other m the alkene remain CIS m the epoxide This is because formation of the bromohydrm involves anti addition and the ensuing intramolecular nucleophilic substitution reaction takes place with mver Sion of configuration at the carbon that bears the halide leaving group... 

The reaction has been extended to include carbanions generated from phosphonates. This is often referred to as the Horner-Wittig or Homer-Emmons reaction. The Horner-Emmons reaction has a number of advantages over the conventional Wittig reaction. It occurs with a wider variety of aldehydes and ketones under relatively mild conditions as a result of the higher nucleophilicity of the phosphonate carbanions. The separation of the olefinic product is easier due to the aqueous solubility of the phosphate by-product, and the phosphonates are readily available from the Arbusov reaction. Furthermore, although the reaction itself is not stereospecific, the majority favor the formation of the trans olefin and many produce the trans isomer as the sole product. 

Carbon—Carbon Bond Formation. Asyimnetiic microbial acyloin condensation was discovered in 1921 (78) and utilized in 1934 in the stereospecific synthesis of (32) (79). 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

The parallel ability of oxiranes to undergo ring opening to carbonyl ylides was first noted in the case of tetracyanooxirane (68T2551), but such reactions have not been widely exploited. The addition to alkenes, leading to formation of tetrahydrofurans, is stereospecific (Scheme... 

Azomethines add with great ease and stereospecificity to carbon-carbon double bonds affording pyrazolidines. They also add to carbon-carbon triple bonds with the formation of pyrazolines. Benzimidazolium iV-imines, e.g. (622), are a special case of azomethines. Its reaction with DMAD yields l-(2-methylaminophenyl)pyrazole (624), which is formed by cleavage of the initial adduct (623) (75JHC225). 

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