Baldwin ring-closure rules

Baldwin s Rules (Suggestions) for Ring Closure JOC 1977, 42,3846 JCSCC 197G, 734, 736, 738... 

In previous sections, we discussed, in a general way, the kinetic and thermodynamic aspects of ring-closure reactions. Baldwin has supplied a more specific set of rules... 

In order to define more precisely the significance of the term favoured, we propose to classify as favoured a reaction whose EM is greater than 0.1 M. This simply means that when such a reaction is run at an initial concentration of 0.1 M, it is favoured over the corresponding intermolecular reaction. The admittedly arbitrary limit of 0.1 M derives from the simple consideration that such a concentration is still acceptable in ordinary preparative work. Accordingly, all but one of the SN2 ring-closure reactions whose pertinent data are plotted in Fig. 27 are classified as favoured processes, since their EM s are greater than 0.1 M. This is consistent with Baldwin s rule that 3- to 1-exo-tet are all favoured processes. 

In addition to nucleophilic reactions, Baldwin s rules also apply to homo-lytic and cationic processes. Table 21 lists rate constants for ring closure of lower -alkenyl radicals (71), in which intramolecular addition to the double bond occurs in the exo-mode (Beckwith, 1981). It is unfortunate that EM-... 

Baldwin, J. E. Rules for Ring Closure J. Chem. Soc, Chem Commun 1976, 734-736. 

In reactions where several different outcomes are possible, the final product distribution reflects the relative free energies of each transition state when the reaction is under kinetic control (Schultz and Lemer, 1993). Baldwin s rules predict that for acid-catalysed ring closure of the hydroxyepoxide [65] the tetrahydrofuran product [66] arising from 5-exo-tet attack will be preferred... 

Fig. 25 The monoclonal antibody 26D9, generated to the jV-oxide hapten [67], catalysed the 6-exo-tet ring closure of [65] regioselectively to yield the disfavoured tetrahydropyran product [68]. This is a formal violation of Baldwin s rules, which predicts a 5-exo-tet spontaneous process to generate tetrahydrofuran derivative [66].

Baldwin, J. E. Thomas, R. C. Kruse, L. I. Silberman, L. Rules for ring-closure Ring formation by conjugate addition of oxygen nucleophiles. J. Org. Chem. 1977, 42, 3846-3852. 

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. 

J. E. Baldwin and M. J. Lusch, Rules for ring closure Application to intramolecular aldol condensations in polyketonic substrates, Tetrahedron 38 2939 (1982). 

The rules of Baldwin (55) for ring closure in trigonal systems (see p. 171 for an introduction) are the following 3- to 7-Exo-Trig processes (152-156) are all favored processes. 3- to 5-Endo-Trig (157-159) are disfavored but 6- and 7-Endo-Triq (160-161) are favored. The literature is replete with examples of 3- to 7-Exo-Trig for instance, lactonization of u-hydroxy-acids and esters are of this type, the formation of lactams from w-aminoacids and also the Dieckmann cyclization of diesters. 

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

Recently, Pelletier and Mody (87) reported an unusual rearrangement of ajaconine (80), via a disfavored 5-endo-trig ring closure, to the more stable oxazolidine ring-containing compound, 7a-hydroxyisoatisine (82). They called attention to apparent violations of Baldwin s cyclization rules (151)... 

For a detailed discussion of the rules for radical ring-closure, see A.L.J. Beckwith, C.J. Easton and A.K. Serelis, 1980, J. Chem. Soc., Chem. Commun., 482. For Baldwin s earlier rules for ring-closure, see J.E. Baldwin, 1976, J. Chem. Soc., Chem. Commun., 734. 

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