Routes to fragmentation

Condensed Pyrroles. Pyrroles can be condensed to compounds containing two, three, or four pyrrole nuclei. These are important ia synthetic routes to the tetrapyrroHc porphyrins, corroles, and bile pigments and to the tripyrroHc prodigiosias. The pyrrole nuclei are joiaed by either a one-carbon fragment or direct pyrrole—pyrrole bond. 

The thermal fragmentation of unsaturated bicyclic 1,4-peroxides, often readily made from 1,4-dienes (Scheme 84), has become an important route to novel bis(oxiranes) (80T833, 81CRV91). 

There are few examples of formation of simple azetidines from [2 + 2] fragments, although this type of approach is important for certain azetidine derivatives, e.g. azetidin-2-ones (see Section 5.09.3). Nitrogen analogues of the Paterno-Buchi route to oxetanes are rare an example involves the photoaddition of 3-ethoxyisoindolone (37) to the enol ether (38) (75JA7288, 72CC1144). 

Complexes 79 show several types of chemical reactions (87CCR229). Nucleophilic addition may proceed at the C2 and S atoms. In excess potassium cyanide, 79 (R = R = R" = R = H) forms mainly the allyl sulfide complex 82 (R = H, Nu = CN) (84JA2901). The reaction of sodium methylate, phenyl-, and 2-thienyllithium with 79 (R = R = r" = R = H) follows the same route. The fragment consisting of three coplanar carbon atoms is described as the allyl system over which the Tr-electron density is delocalized. The sulfur atom may participate in delocalization to some extent. Complex 82 (R = H, Nu = CN) may be proto-nated by hydrochloric acid to yield the product where the 2-cyanothiophene has been converted into 2,3-dihydro-2-cyanothiophene. The initial thiophene complex 79 (R = R = r" = R = H) reacts reversibly with tri-n-butylphosphine followed by the formation of 82 [R = H, Nu = P(n-Bu)3]. Less basic phosphines, such as methyldiphenylphosphine, add with much greater difficulty. The reaction of 79 (r2 = r3 = r4 = r5 = h) with the hydride anion [BH4, HFe(CO)4, HW(CO)J] followed by the formation of 82 (R = Nu, H) has also been studied in detail. When the hydride anion originates from HFe(CO)4, the process is complicated by the formation of side products 83 and 84. The 2-methylthiophene complex 79... 

Pieces of various routes to moxalactam have been published from which the following may be assembled as one of the plausible pathways. The benzhydrol ester of 6-aminopenici 11 anic acid ( ) is -chlorinated and treated with base whereupon the intermediate sulfenyl chloride fragments to ). Next, displacement with propargyl alcohol in the presence of zinc chloride gives predominantly the stereochemistry represented by dia-stereoisomer The side chain is protected as the phenyl-... 

High pressure cycloaddition of cytraconic anhydride (140) with 2-substituted furans 142 afforded, cxo-diastereoselectively but unregioselectively, bicyclic cycloadducts 143 and 144 that have been used in straightforward routes to CD-ring fragment of paclitaxel [55] (Scheme 5.22). The cycloadducts were then... 

As the availability of crystal structures increased in the early 1990s, a number of experimental and computational methods were developed to use the structure of the protein target as a route to discover novel hit compounds. The methods include de novo design, virtual screening, and fragment-based discovery. These developments are covered in more detail in the later chapters of this book, but their main features can be summarized as follows. 

Fig, 2 (a) Synthetic routes to carbohydrate fragments from AGPs... 

K. C. Nicolaou s group at Scripps Research Institute developed two synthetic routes to epothilone A. One of the syntheses involves closure of the lactone ring as a late step. Three major fragments were synthesized. The bond connection at C(6)-C(7) was made by an aldol reaction. The C(12)-C(13) bond was formed by a Wittig reaction and later epoxidized. The ring was closed by macrolactonization. 

Equation (51) has a clear physical interpretation. Recalling the lineshape for a single excitation route, where fragmentation takes place both directly and via an isolated resonance [68], p oc (e + q)2/( 1 + e2), we have that 8j3 is maximized at the energy where interference of the direct and resonance-mediated routes is most constructive, e = (q I c(S )j2. In the limit of a symmetric resonance, where q —> oo, Eq. (51) vanishes, in accord with Eq. (53) and indeed with physical intuition. The numerator of Eq. (51) ensures that 8]3 has the correct antisymmetry with respect to interchange of 1 and 3 and that it vanishes in the case that both direct and resonance-mediated amplitudes are equal for the one-and three-photon processes. At large detunings, e —> oo, and 8j3 of Eq. (51) approaches zero. 

A few routes to new silenes, usually involving flash vacuum pyrolysis at high temperatures, have been reported. Silenes were proposed as the result of the thermal expulsion of trimethylmethoxysilane, or a similar volatile fragment, from the starting material but frequently, proof that the silenes proposed to account for the observed products were in fact formed was not provided.116 119 The other thermal route employed was the retro-Diels-Alder regeneration of a silene from an adduct with an aromatic compound—often a 9,10-anthracene or 1,4-naphthalene adduct or, in some cases, a 1,4-benzene adduct, as illustrated in Eq. (19).120... 

Sources of catalytically active palladium(O) typically arise from ligand dissociation from coord-inatively more saturated Pd° complexes871-880 or from reduction of a Pd11 species.353,881 Another route to catalytically active (P—P)Pd fragments is the dissociation of the dinuclear complexes [(//-P—P)Pd]2.882 Complexes [(/r-dcpm)Pd]2 and [(/r-dtbpm)Pd]2 were obtained from the reductive elimination of ethane from dimethylpalladium(II) complexes (dippm = bis(diisopropylphosphino)methane dcpm = bis(dicyclohexylphosphino)methane dcpm = bis(di-t-butylphosphino)methane).883... 

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