Electrophilic iterative

The initial discussion in this chapter will focus on addition reactions. The discussion is restricted to reactions that involve polar or ionic mechanisms. There are other important classes of addition reactions which are discussed elsewhere these include concerted addition reactions proceeding through nonpolar transition states (Chapter 11), radical additions (Chapter 12), photochemical additions (Chapter 13), and nucleophilic addition to electrophilic alkenes (Part B, Chi iter 1, Section 1.10). 

As broadly demonstrated in aromatic DoM chemistry (90CRV879), iterative metalation of pyridyl O-carbamates are synthetically useful processes. Thus, sequential metalation reactions of 3- and 4-pyridyl O-carbamates with electrophiles that provide incipient DMGs afford 3,4,5-trisubstituted pyridines 327, 328, and 329, respectively (Scheme 99) (85JOC5436). 

The first step in this minimalistic transcription/translation process that mimic genealogical criteria in Fig. 46 involves Michael addition of methyl acrylate to the nucleophilic ammonia surface to produce an electrophilic, carbomethoxy functionalized surface, followed by reaction with ethylenediamine to translate the functionalized dendrimer surface back to a nucleophilic primary amine functionalized surface. This iterative sequence is the key in providing alternating nucleophilic... 

In a further study, comprising of a proof of concept sequence to natural product like libraries, Smith and coworkers [64] have developed another Type II ARC, four-component domino process in an iterative manner employing linchpins (—)-176, 188, and 1,3-dithiane 180 as initial nucleophile and allyl bromide as final electrophile (Scheme 4.37). The four-component adduct 189, thus obtained in 59% yield as diastereomeric mixture (1.25 1 at carbinol site) was converted to natural product like macrolactone 190 in five steps in overall yields of 12 and 13% (Scheme 4.37). 

The linear or open arrangement of a three-ci iter-four-electron system H3 bears a close resemblance to the transition state geometry associated with a nucleophilic attack on a tetrahedral carbon center shown in 7.24. Corre ondtngly, the triangular or closed arrangement of a three-center-two-electron system H3 is related to a front-side electrophilic attack as shown in 7.25. The relevant orbitals at the tetrahedral carbon consists of the C—X bonding and antibonding orbitals OcX Sxt... 

The distannane mediated organic radical addition to A -acyliminium ions [13], and the benzylic radical addition to A/ -acyliminium ions which proceeds via radical/cation/radical cation chain mechanism [14] show that the cation pool can be utilized as good nucleophilic radical acceptors because of their strong electrophilic character. Iterative molecular assembly based on the cation pool method lead to the efficient formation of dendritic molecules [15]. The manipulation of the cation pool in the microflow system realized an efficient... 

The Sj l reaction of R Sn ions is quite versatile and affords triorganylstannyl compounds. The sequence of S, reactions to synthesize stannanes followed by a Pd-catalyzed process (Stille reaction) with electrophiles is a powerful synthetic tool this sequence can be iteratively repeated to synthesize complex molecules. 

The most obvious method to install the C1-C2 alkene of a dendralene is an olefination reaction (Scheme 1.19), but it has seen very little use, because of the propensity of 2-carbonyl-1,3-butadiene derivatives to undergo rapid Diels-Alder dimerization [81]. In fact, the only successful uses of 2-carbonyl-1,3-butadienes in such processes feature substrates stabilized by 1,1-disubstitution and a 4Z substituent. Such an example is the iterative formylation/olefination sequence reported by Yoshida and coworkers (Scheme 1.20) [82]. A selective, single electrophilic formylation followed by a Wittig reaction gave hexa-substituted... 

In addition to the methyl and benzyl halides that have generally been utilized with the previously described auxiliaries for enolate alkylation, Myers demonstrated that aliphatic and 3-branched alkyl halides may also be readily employed. A powerful synthetic application was disclosed with the iterative syntheses of the various configurational permutations of 1,3,5-trialkyl-substituted carbon chains (175-178, Scheme 3.28) [99]. Moreover, epoxides [100] and a-fluorocarboxamides [101] also served well as electrophiles. 

The terms linear and iterative refer to reaction sequences that make multiple use of the metal the hapticity of the electrophile decreases with each step in a linear... 

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