Anti addition reactions intramolecular cyclization

Intramolecular reaction of an allylsilane and an aldehyde was performed to prepare cyclic compounds as illustrated in Eq. (90) [233], which shows a high diastereoselec-tivity. The cyclization of optically active allylsilane proceeds stereoselectively in a manner consistent with the antiS l mechanism (Eq. 91) [234]. Development of a new reagent with a bis-allylsilane moiety effected tandem inter- and intramolecular cyclizations to give cyclic compounds as exemplified in Eqs (92) [235] and (93) [236-238]. In Eq. (92), the double addition product initially formed underwent a pinacol-type rearrangement under the influence of TiCU to give, eventually, the methyl cyclopentyl ketone. Further examples of intramolecular cyclization of allylsilanes are summarized in Table 8. 

The aqueous medium influences not only the reaction rate but also the stereoselection of the aldol addition. One significant example [13] is the intramolecular cyclization of ketoaldehyde depicted in Scheme 7.2. In organic solvents there is a preference for syn or anti adduct depending on the presence of coordinating cations (K, Na, Li, MgBr ) or a complexing agent such as... 

A rationale for the cz s-selective cyclization for the intramolecular homoal-lylation of oo-dienyl aldehyde 64 is illustrated in Scheme 16. The scenario is essentially the same as the one proposed for the intermolecular reaction, and a Ni(0) species undergoes oxidative addition upon the diene and the aldehyde moieties through a conformation placing the aldehyde substituent and the diene anti to each other. An intermediate 66 undergoes (>-II elimination and czs-reductive elimination of the thus-formed Ni - H complex to produce 65. 

Few reactions of intramolecular conjugate addition of co-amino groups to alkenes with an electron-withdrawing group are known. Both the E- and Z-isomer of 1 cyclize to the same pyrrolidine 2 with a, 2-anti preference, however, more of the. vvn-isomcr is produced from the F-isomer than from the Z-isomer. The product ratio is determined by separately isolated derivatives of the products 268 74. Similar reactions with lower diastereomeric ratios are known75. 

DFT computations showed that the intramolecular addition of the aryllithium generated from 425 occurs on the central carbon atom of the allenic moiety to yield the intermediate 427 from which lithium ethoxide is eliminated to furnish the benzofuran product 426. Both cyclization processes were found to pass through low-lying transition states, as it would be expected for fast reactions at low temperatures [123]. Further explorations on the anti selectivity in the intramolecular carbolithi-ation by DFT computations revealed additional details regarding the mechanism of this carbocyclization and led the authors to conclude that such a transformation is controlled by the appropriate molecular editing [123]. The synthesis of functionalized heterocycles can be relatively easy to achieve by intramolecular carbometallation reactions. For example, Kunz and Knochel [124] recently reported the preparation of benzothiophene scaffolds 429 by copper-catalyzed carbomagnesiation ofalkynyl thioethers 428 (Scheme 10.148). 

Since the early success of Decicco et al. [19] in extending the boronic acid cross-coupling to an intramolecular system, more examples of this approach have appeared in the literature (Scheme 5.5). Snapper and Hoveyda reported a total synthesis of the anti-HIV natural product chloropeptin 1 in which the crucial biaryl ether moiety was constructed via the Cu-mediated reaction (Scheme 5.5) [20]. Thus, treatment of the boronic ester 10 with NalO liberates the boronic acid, which then cyclizes under Cu(OAc)2 to give the biaryl ether 11, a precursor to the final target. In this case, the addition of 10 equiv. of methanol was critical for efficient intramolecular cross[Pg.210]

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