Medium sized fragments

In the next step, the molecule is fragmented into ring systems and acyclic parts. Ring systems are then separated into small and medium-sized rings with up to nine atoms and into large and flexible systems. 

Keywords Medium-sized ring lactams. Macrocyclization. Ring expansion. Rearrangement, Fragmentation... 

Consequentially, the driving force had to be increased on synthesizing medium-sized ring lactams by means of a fragmentation. Until now, by far the majority of reactions involved the breaking of a small annulated ring (Exception ... 

This reaction can be used in synthesis of medium-sized rings by cleavage of specific bonds. An example of this reaction pattern can be seen in a fragmentation used to construct the ring structure found in the taxane group of diterpenes. 

Fragmentation of alkoxy radicals finds use in construction of medium-size rings.364 One useful reagent combination is phenyliodonium diacetate and iodine.365 The radical formed by fragmentation is normally oxidized to the corresponding carbo-cation and trapped by iodide or another nucleophile. 

Similarly, bicyclic hemiacetals fragment to medium-size lactones. 

Up to now, we have seen how the "heuristic principles" can be applied to both linear and cyclic systems which we could call "normal systems". When some unusual structural features -such as quaternary carbon atoms, medium-sized rings or bridged systems- are found in the molecular structure under consideration, one may assume that they are derived either from a rearrangement or from an internal fragmentation [1]. 

Rarey, M., Weeing, S., and Lengauer, T. Placement of medium-sized molecular fragments into active sites of proteins. 

The [i,y fragmentation is known as Grob fragmentation. Its synthetic application is usually in the construction of medium-sized rings by fragmentation of fused ring systems. 

The present analysis relies on - and extends - the comprehensive theoretical study of Refs. [23,24] on the multi-state interactions in the manifold of the X — E states of Bz+. Like this recent work, it utilizes an ab initio quantum-dynamical approach. In Refs. [23,24] we have, in addition, identified strong coupling effects between the B — C and B — D electronic states, caused by additional conical intersections between their potential energy surfaces. A whole sequence of stepwise femtosecond internal conversion processes results [24]. Such sequential internal conversion processes are of general importance as is evidenced indirectly by the fluorescence and fragmentation dynamics of organic closed-shell molecules and radical cations [49,50]. It is therefore to be expected that the present approach and results may be of relevance for many other medium-sized molecular systems. 

Hydrogen abstraction under conditions similar to those in Section 3.8.1 may occur also from nitrogen compounds, with formation of amidyl free radicals. The results vary, depending on the substrate for example, 6-amino derivatives of steroids were converted into TV-substituted pyrrolidines [127], Medium-sized lactams underwent transannular cyclization to bicyclic lactams [128], and bicyclic carbinolamides afforded mainly -fragmentation products (Table 3.7). 

The electrochemical reduction of y-oxoesters like 115, synthesized via the cyclopropane route, results in cyclization with participation of the olefinic unitn>. This reaction provides interesting cyclopentanol derivatives, which can be transformed to the corresponding cyclopentenes. Alternatively a fragmentation to medium sized ketones like 116 occurs after saponification and anodic oxidation 77>. 

Molander has developed a Sml2-mediated Barbier cyclisation-Grob fragmentation sequence for the synthesis of medium-sized carbocycles.134 For example, treatment of mesylate 115 with Sml2 and catalytic Nil2 gave cyclo-decenone 116 in excellent yield (Scheme 5.82). 

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