Baldwin’s rules for ring closure

The formation and the hydrolysis of acyclic and cyclic acetals have been studied in rather great detail [91]. Several reviews on this topic are available [92] and some comments have been made [13] concerning the carbohydrate series. We have shown in Schemes 1,2, and 3 that a common feature of this reaction seems to be the intermediacy of an oxocarbenium ion. However, the cyclization of such an intermediate has been questioned more recently [93] in the light of the Baldwin s rules for ring closure [94]. At least for the five-membered ring, an SN2-type displacement mechanism far the protonated form (B) of die hemiacetal (A) (favorable 5-exo-tet cyclization) has been proposed rather than the unfavorable 5-endo-trig cyclization of the oxocarbenium ion (C) (Scheme 5). Except when the formation of the enol ether (D) is structurally impossible, the intermediacy of such a compound remains feasible. 

Step 4 Intramolecular aldol condensation favors the five-membered ring over the seven-membered ring (see Baldwin s rules for ring closure). 

An astounding aspect of antibody catalysis is the ability of these progranmiable biocatalysts to preferentially form the less thermodynamically favored product (66, 71-74). The intramolecular cyclization reaction of frons-epoxyalcohol 18 is an archetypal example of antibody catalysis of a disfavored transformation, which preferentially forms the tetrahydrofuran 19 under nncatalyzed conditions due to the overwhelming stereoelec-tronic constraints predicted by Baldwin s rules for ring closure (Fig. 9) (75, 76). 

Cyclization Reactions-Baldwin s Rules for Ring Closure 231... 

CYCLIZATION REACTIONS-BALDWIN S RULES FOR RING CLOSURE... 

In Chapter 31 we discussed Baldwin s rules for ring closures such as these. The unreactivity of the trichloromethyl group is related to the unreactivity of dichloromethane see p. 804. 

Gilmore, K. and Alabugin, TV. (2011) Cyclizations of alkynes revisiting Baldwin s rules for ring closure. Chemical Reviews, 111(11), 6513-6556. 

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