Cyclizations 6- endo-trigonal

At first, acid-catalyzed cyclization of Hofmann degradation products was undertaken however, the cyclization proceeded via the 5-exo-trigonal mode instead of the 6-endo-trigonal mode, resulting in no benzo[c]phenanthridine skeleton. Dyke and Brown (114-117) reinvestigated Perkin s results (118,119) and established the structure of the cyclized products 196 and 197 derived from the methine base 194 (Scheme 36). Onda et al. (120,121) obtained the five-membered spiro compounds 198 and 199 by treatment of 195 with dilute hydrochloric acid. 

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). 

In conclusion, except in very special cases, reasonable yields of cyclized products cannot be expected in the Cy4/Cy5 case since if they are formed the (Cy 4) radical will open readily (i.e., it is the opening and not the closing process which is favored). The absence of cyclization toward the (Cy 5) radical is an excellent example of the disfavored 5-endo-trigonal closure in accord with Baldwin s rules. 

This reaction is useful for cyclizations involving 6-endo-trigonal (eq 14) and allowed 1-endo trigonal processes (eq 15), but not for those involving 5-endo trigonal processes (eq 16). These observations are consistent with the Baldwin rules. 

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. 

One typical radical reaction is cyclization. This cyclization has been used as an indirect proof for radical reactions and a strategic method for the construction of 5- and 6-membered cyclic compounds. The experienced rule for the cyclization is Baldwin s rule [19]. There are two cyclization modes, i.e. exo and endo moreover, there are three types of hybridization in a carbon atom, sp3 (tetrahedral tet), sp2 (trigonal trig), and sp (digonal dig). Baldwin s rule is the cyclization rule based on the experimentally obtained cyclization results. The cyclization mode and kinds of hybridization in an intramolecular radical acceptor are shown in Figure 1.15. 

Thus, it is called exo , when the cyclization occurs on the inside of the unsaturated carbon-carbon bond, and it is called endo , when the cyclization occurs on the outside of the unsaturated carbon-carbon bond. Moreover, it is tet (tetrahedral 109.5°), when the carbon-carbon bond at the reaction site is sp3 hybridization it is trig (trigonal, 120°), when the unsaturated carbon-carbon bond at the reaction site is sp2 hybridization and it is dig (digonal, 180°), when the unsaturated carbon-carbon bond at the reaction site is sp hybridization. For example, there are two types of cyclization manner in 5-hexen-l-yl radical, exo-trig and endo-trig, based on the above classification. Since a 5-membered cyclopentylmethyl radical is formed through exo-trig cyclization, it is finally... 

On the other hand, cyclization to TM 7.8 requires the approach of the nucleophile under a small angle, approximately 90°, and the endb-position of the double bond, both stereoelectronically unfavorable. Generally, the Baldwin rules state that cyclization to a five-membered ring is favored when the reacting double bond on the trigonal C-atom is exo and disfavored when it is endo. In Table 7.1, the Baldwin... 

A paper on the application of Baldwin s rules (see Chapter 6) to specific heterocyclic examples has appeared, and more are anticipated in this potentially fruitful area. Compounds have been examined as substrates for disfavoured 5-Endo-Trigonalring forming reactions. Ketols (1) and (2) did not cyclize to the furanones (3) and (4) respectively, under basic conditions, but the reactions were smoothly achieved with acid catalysis a result best explained by the intermediacy of the enol (5) using the 5-Exo-Trigonal process (Scheme 1). Treatment of the unsaturated... 

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