Alkenes synthon generation

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

The ready availability of starting materials, such as dienes and alkenes, has contributed to the popularity of the Diels-AIder reaction. Unfortunately, this is not true in [3 + 2] cycloadditions. While die C2 unit is well represented by simple unsaturated molecules as in the Diels-AIder reactions, the source of the odd-numbered Att fragment is less obvious because it is not a common stable entity. Hence, the success of using the [3 + 2] methodology in a synthetic sequence depends critically on the effective generation, reactivity and selectivity of this Cs synthon. 

Padwa and coworkers found that a-cyanoaminosilane 12a is a convenient synthon for azomethine ylide 15 which is extensively used in heterocyclic synthesis [7]. AgP has been adopted to generate the ylide 15 from 12a for the preparation of pyrrolidine derivative 14 (Sch. 4). Various dipolarophiles including A-phenylmaleimide (13) can be used for the cycloaddition. When iV-[(trimethylsilyl)methyl]-substituted indole 16 is reacted with AgP in the presence of maleimide 13, pyrrolo[l,2-a]indole 17 is formed in good yield, retaining the CN group [8]. A silver-bonded carbonium ion is assumed to be a reactive intermediate. Reaction of a cyano-substituted azomethine ylide, derived from (silylmethylamino)malononitrile 12b and AgP, with methyl propiolate (18) provides 3-carbomethoxy-A-benzylpyrrole (19) [9]. Epibatidine, a novel alkaloid, was successfully synthesized by employing the [3 + 2] cycloaddition of azomethine ylide with electron-deficient alkenes as a key step [10]. 

As the proceeding chapters demonstrate, Ni(0)- and Pd(0)-catalyzed [3-1-21-cycloadditions of methylenecyclopropanes with alkenes open a new, simple, and useful route to a number of substituted methylenecyclopentanes. This catalytic generation of a trimethylenemethane synthon and its addition to olefinic double bonds not only lead to five-membered rings but also introduce an exocyclic methylene group, which is a useful functionality for further structural elaboration. 

For the enantioselective preparations of chiral synthons, the most interesting oxidations are the hydroxylations of unactivated saturated carbons or carbon-carbon double bonds in alkene and arene systems, together with the oxidative transformations of various chemical functions. Of special interest is the enzymatic generation of enantiopure epoxides. This can be achieved by epoxidation of double bonds with cytochrome P450 mono-oxygenases, w-hydroxylases, or biotransformation with whole micro-organisms. Alternative approaches include the microbial reduction of a-haloketones, or the use of haloperoxi-dases and halohydrine epoxidases [128]. The enantioselective hydrolysis of several types of epoxides can be achieved with epoxide hydrolases (a relatively new class of enzymes). These enzymes give access to enantiopure epoxides and chiral diols by enantioselective hydrolysis of racemic epoxides or by stereoselective hydrolysis of meso-epoxides [128,129]. 

Organyltellurolates are useful synthons in organic chemistry.Tellurolates can be alkylated or arylated to afford diorganyl tellurides and they add to alkenes and alkynes. The latter reaction is both regioselective and transstereospecific. They can also be utilized in the generation of tellurium-containing heterocycles. 

In studies on carbapenem synthons, a series of monocyclic j3-lactams of type 27 and 29 were generated with an exo-alkene group at C-3 [38]. The conjugated double bonds herein could be reduced easily under microwave-assisted CTH conditions with stereospecificity leading to only cis jS-lactams of type 28 and 30, which is highly desirable (see Scheme 18). 

Aside from the standard use of natural synthons and the routes via double umpolung, there is the possibility of enlisting 1,3-dipolar cycloadditions to form 7,5-difunctionalized molecular skeletons. Typical examples include the addition of nitrones, silyl nitronates [94], or nitrile oxides to alkenes. The initial products of the latter cycloaddition are isoxazolines, which may be refunctionalized in various ways (Scheme 2.52). When this generates sensitive functionalities, refunctionalization may be postponed until later in the synthesis sequence [95]. 

The utilization of the Wittig reaction to prepare functionalized alkenes such as Z-vinyl halides has also been demonstrated since the early 1990s (Fig. 2) [12]. The iodoalkyl phosphonium salt is deprotonated with sodium hexamethyldisilazane to yield the ylide that reacts with aldehydes to generate the Z-alkenyl halides in good to excellent selectivity. Not only disubstituted Z-alkenyl halides, but also trisubsti-tuted ones can be prepared using this method, albeit with moderate chemical yields [13]. These products are useful synthons in organic synthesis, especially in cross coupling reactions. 

---