Chiral neighboring group participation

Under more basic conditions, a-elimination predominates and insertion of the carbene 40 to the solvent gives racemic 22. Non-basic and poorly nucleophilic conditions allow neighboring group participation to form the rearranged substitution product 23 with complete chirality transfer. The participation can be considered as an intramolecular nucleophilic substitution, and does occur only when it is preferable to the external reactions. Under slightly basic conditions with bases in HFIP, participation is allowed, and the weak base can react with the more electrophilic vinylic cation 21 (but not with the iodonium ion 19). A suitably controlled basicity can result in the formation of cycloalkyne 39, which is symmetrical and leads to racemization. These reactivities are illustrated in Scheme 6. 

Table 21 Differential Arrhenius parameters for the competing neighboring-group participation to the unimoplecular H2O loss in the chiral oxonium ions 26 and 28 (A = H)...

This role of the O, called neighboring-group participation, always leads to an inversion of configuration if the attacked C is a chiral center (stereocenter). 

Discrimination can readily be observed between the two possible modes of attack on a carbonium ion (195 196 and 195 197 when the nucleophile is part of the substrate. In such cases, the phenomenon of neighboring group participation is observed (for a review, see ref. 69). For example, solvolysis of the erythro-tosylate isomer 202 in acetic acid gave largely the erythro-acetate isomer 204 vi a the chiral bridged ion 203, whereas the threo isomer 205 yielded a racemic mixture of threo products 207A and 207B via the achiral intermediate 206 (70). 

Neighboring Group Participation Using Chiral Auxiliaries to Obtain 1,2-cts-Glycosides... 

However, even without standard neighboring group participation, predominant retention may occur, as in the following example. The chiral epoxy alcohol 6 gives a mixture of 7A and B in 78-92% total yield. The isomer 7A, which shows retention of configuration, predominates 3 1. At O C the ratio of 7A to 7B is 2 1. ... 

Acidic hydrolysis affords the hydroxyalkylurethanes 71, which are cleaved im-der basic conditions with neighboring group participation by the hydroxy group. The use of less basic barium hydroxide, as proposed in ref [62], is superior when chiral substrates, prone to racemization, are handled. 

Neighboring group participation in Mitsunobu reactions occurs frequently if intermediate aziridinium or episulfonium cations can be formed. During such a process, subsequent attack by the nucleophile can lead to changes in ring size or products with retention instead of inversion at chiral alcohol centers. 

Reaction with Phenols and Other Oxygen Nucleophiles. When alcohols react with phenols, DEAD, and TPP, the corresponding aryl alkyl ethers are produced. A tertiary amine may facilitate the reaction. In general, the reaction proceeds with clean inversion of chiral secondary carbinol centers (eq 2 AH = a phenol). Depending on the structure of the substrate, al-lylic rearrangement and neighboring group participation can... 

Ramachary, D. B., Madhavachary, R., Prasad, M. S. (2012). Observation of neighboring ortho-hydroxyl group participation in organocatalytic asymmetric sequential Michael-lactonization reactions synthesis of highly substituted chiral spirodihydro-coumarins. Organic Biomolecular Chemistry, 10, 5825-5829. 

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