Baldwins Rules

In all cases examined the ( )-isomers of the allylic alcohols reacted satisfactorily in the asymmetric epoxidation step, whereas the epoxidations of the (Z)-isomers were intolerably slow or nonstereoselective. The eryfhro-isomers obtained from the ( )-allylic alcohols may, however, be epimerized in 95% yield to the more stable tlireo-isomers by treatment of the acetonides with potassium carbonate (6a). The competitive -elimination is suppressed by the acetonide protecting group because it maintains orthogonality between the enolate 7i-system and the 8-alkoxy group (cf the Baldwin rules, p. 316). 

In the present chapter, however, because the problem is considered from a retrosynthetic point of view, we will distinguish only between heterolytic and homolytic disconnections -to which we will refer to as "retro-annulations"- and concerted or "pericyclic (or cheletropic) cycloreversions". In the same way that Woodward-Hoffmann rules [2] apply to pericyclic reactions, the Baldwin rules [3] may be said to apply to heterolytic as well as to homolytic "monotopic" annulations (see Table 6.1). Although in the preceding Chapter (see 5.5) we have already described some radical "monotopic" annulations, later on in this Chapter (see 6.1.3) and mainly in Chapter 7 we will refer to some new methods, syntheses and strategies which have been developed recently. 

According to the Baldwin rules (see Table 6.1), the exo-cyclisation leading to the primary radical (9) is favoured over the enJo-cyclisation which would lead to the more stable secondary radical (10), the stereoelectronic factors playing a fundamental role in the observed selectivity. 

Whereas the cyclization of chalcones or analogous compounds leads to six-membered rings, in accordance with the Baldwin rules [182], the same reaction with a triple bond can afford compounds with six-membered (6-endo-dig) or five-membered (5-exo-dig) rings, depending on the reaction conditions. This property... 

While the Baldwin rules [44] indicate both 5-exo-tri and 6-endo-in modes of cycliz-ation are favorable, only the latter is observed in the following reaction [45]. 

According to the Baldwin rule, the exo cyclization mode is favored in intramolecular reactions of alkynyloxiranes with alcohols to afford cyclic ethers. However, the unfavorable endo cyclization mode is observed by the complexation. Thus exclusive endo cyclization of epoxide complex 146 takes place regioselectively to give 147, without forming the five-membered ether 148 by exo mode reaction [37]. 

Despite being forbidden by the Baldwin rules (5-mdo-trig ring opening see Section 9.2), cyclohexadienoic acid derivatives such as that required for this synthesis can be prepared by base-induced ring scission of 7-oxanorbornene derivatives, presumably because of the high strain-energy of norbornenes. The required 7-oxanorbornene, in turn, should be readily accessible from furan and an acrylate via the... 

In summary, certain reactions with diterpenoid alkaloid imines proceeded by a disfavored 5-endo-trigonal process, whereas in other cases, such as the reactions with glycidol, a favored 6-endo-trigonal process was followed. The Baldwin rules should be modified to accomodate the exceptional behavior of the tertiary immonium salts. Recently, examples of similar reactions demonstrating the violation of the Baldwin cyclization rules have been reported (156-158). 

Cyclocondensation reactions starting from two components are possible only when both have two reactive centers. By far the most common version is an initial electrophilic/nucleophilic interaction yielding a linear product, followed by a second electrophilic/nucleophilic interaction in the final cyclization step (85MI2). The ring-forming condensation step is controlled by a series of rules (Baldwin rules 76CC734). There are various types of such interactions (Scheme 19). 

Generation of a radical in a molecule that contains a site of unsaturation presents an opportunity for (yclization. These types of radical cyclizations have been developed into very useful synthetic reactions. The synthetic utility of these cyclizations is enhanced by the abhity to predict the regiochemistry of cyclization by applying the Baldwin rules. The Baldwin rules cover the formation of three- to seven-membered rings by various reactions and are based on consideration of both kinetic and thermodynamic factors. (See Beckwith, A. L. J. Easton, D. J. Serelis, A. K. J. Chem. Soc., Chem. Commun. 1980, 482-483, and Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734-736.)... 

The Baldwin rules distinguish two types of ring closure, exo and endo. 

It should be noted that the radical cyclization proceeds to yield a five-membered ring and not a six-membered one. This is predicted by the Baldwin rules for ring-closure and is classified as a 5-exo-trig closure ". LiAlH4 has also been used to generate the cyclopropyl radical which also underwent a 5-exo-trig ring-closure. ... 

These findings have been rationalized by the rule offive (Srinivasan and Carlough, 1967), according to which five-membered cyclic biradicals are preferentially formed, as shown in Scheme 15. (Cf. also the Baldwin rules for radical cyclizations, Baldwin, 1976.)... 

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