Synthesis Introducing Functionality

Tran orm-based or long-range strategies The retrosynthetic analysis is directed toward the application of powerful synthesis transforms. Functional groups are introduced into the target compound in order to establish the retion of a certain goal transform (e.g., the transform for the Diels-Alder reaction, Robinson annulation, Birch reduction, halolactonization, etc.). 

Tetraalkyllead compounds can also be used as starting materials for the synthesis of functionalized and specific organoplumbanes. In the latter case, cleavage of one or more of the attached alkyl groups is achieved so as to introduce subsequently new groups, different from the original ones. 

Lautens also used this nickel-catalyzed hydroalumination methodology in the total synthesis of ionomycin 145. The starting compound was a [3.2.1]oxabicyclic alkene 143.144 Their rigid bicyclic structures can be used to introduce functional groups in a highly stereoselective manner. The synthesis of the key intermediate 144 involves the slow addition of DIBAL to the oxabicyclic alkene and the Ni(COD)2/(6T)-BINAP in toluene to afford 144 in 95% yield and 93-95% ee. (Scheme 18). 

Most immobilization methods require modification of the ligands for anchoring to the support by introducing functional groups such as vinyl, trialkoxysilyl, sulfonic acid, and amino groups. The consequence is often a more elaborate synthesis of the ligand, which adds to the costs of an immobilized catalyst. However, two interesting approaches were developed in recent years, when unmodi-... 

Methods for introducing functional groups into Co(C2B3)M triple-deckers, important in many synthetic strategies for constructing multicage oligomers and polymers (Section 3.01.4.5), have been developed with the synthesis of... 

The idealized mimetic 34 (Scheme 14) was designed to incorporate the ability to introduce functionality at each of the positions R1, R2, R3, and R4, and both an amino and carboxy terminus for coupling to peptide chains. The stereospecific and regiospecific synthesis of a molecule which contains six nonadjacent asymmetric centers proved to be a difficult task. Model studies for the synthesis were performed. 88 The salient feature of this synthesis was an acylimminium cyclization 89 coupled with a tin hydride induced radical cyclization (Scheme 18). 90 Unfortunately, we were not able to readily relate the introduction of the... 

The three themes of the symposium selective hydrogenation, selective oxidation and acid-base catalysis were introduced by four plenary lectures and two invited communications. A panel concerned with the future of zeolites and other shape-selective materials for fine chemical synthesis was conducted by specialists in the field D. Barthomeuf (University of Paris 6), E. Derouane (University of Namur), L. Forni (University of Milan), M. Gubelmann (Rhone-Poulenc, St Fons), W. Hoelderich (BASF, Ludwigshafen) and G. Perot (University of Poitiers). An exhibition of equipment was held during the symposium on October 3 and 4. Over 20 firms exhibited equipment, chemicals and catalysts which were of interest to researchers involved with the synthesis of functional compounds by heterogeneous catalysis. 

Koch aldehyde synthesis) introduces the H-—C=0 function into reactive aromatic compounds such as 2-naphthalenol. The necessary reagents are HCN, HCl, and a metal-halide catalyst (ZnCI2 or AICI3), and the initial product must be treated with... 

Finally, Thiele acetoxylation of quinones, by treatment with acetic anhydride and sulfuric acid, is another excellent method of introducing functionality at an alkene carbon atom, for further synthetic elaboration (equation 50)196. This reaction was recently used as a key synthetic step in the total synthesis of metachromin-A, a useful sesquiterpene quinone moiety197. 

Catalytic oxy-palladation is an extremely useful method for the synthesis of functionalized THF and tetrahydropyran moieties. This reaction is brought about simply by treating a 1,4- or 1,5-hydroxy alkene with 0.1 mol-eq of Pd(II) salts and copper(I) chloride in DMF, with oxygen (equation 181)655. If this reaction is carried out in the presence of carbon monoxide in methanol, then an ester moiety is introduced into the product molecule (equation 182)656-658. If an alkene is introduced in place of the CO, then a tandem vinylation reaction also takes place (equation 183)659. 

Polymeric supports can also be used with advantage to form monofunctional moieties from difunctional (Hies. Leznoff has used this principal in the synthesis of sex attractants on polymer supports (67). Starting from a sheap symmetrical diol he blocked one hydroxyl group by the polymer. Functionalization of cross-linked polymers is mostly performed by chloromethylation (65). A very promising method to introduce functional groups into crosslinked styrene-divinylbenzene copolymers is the direct lithiation with butyllithium in presence of N,N,N, N -tetramethyl-ethylenediamine (TMEDA) (69, 70). Metalation of linear polystyrene with butyl-lithium/TMEDA showed no exchange of benzylic hydrogen and a ratio of attack at m/p-position of 2 1 (71). In the model reaction of cumene with amylsodium, a kinetic control of the reaction path is established. After 3h of treatment with amyl-sodiuni, cumene is metalated 42% in a-, 39% m-, and 19% p-position. After 20h the mixture equilibrates to affort 100% of the thermodynamically more stable a-prod-uct (72). 

The overall reaction is the substitution of an electrophile (E+) for a proton (H+) on the aromatic ring electrophilic aromatic substitution. This class of reactions includes substitutions by a wide variety of electrophilic reagents. Because it enables us to introduce functional groups directly onto the aromatic ring, electrophilic aromatic substitution is the most important method for synthesis of substituted aromatic compounds. 

The replacement of carbon atoms of cyclobutane by heteroatoms introduces functionalities which show increased reactivity resulting from Ae ring strain. This often leads to unusual properties which make four-membered heterocycles useful as synthetic intermediates.However, it also adds a new dimension of difficulty concerning the synthesis of these heterocycles. A valuable source of four-membered heterocycles uses the combination of ir-bonds. This section is devoted to a survey of these reactions with special focus on selectivity in all of its forms. Photochemical cycloadditions are not discussed here since they are covered elsewhere. In several instances, reactions will be described which can formally be considered as combinations of ir-systems but probably take alternate pathways. However, since the real mechanisms are often unknown, these very useful reactions will be discussed here. 

Sigmatropic rearrangement is a method for the synthesis of functionalized alkenes, aromatics, al-lenes or alkynes. The C—X bond of the starting material (1) serves to introduce the C—Y bond into the molecular framework regioselectively and often stereoselectively. The newly formed C—X bond can be carbon-carbon or carbon-heteroatom. In the following, 2,3-rearrangements will be discussed in this order. 

Fig. 3 Synthetic scheme of synthesis of functional polyrotaxanes, in which carboxyl groups were introduced into hydroxyl groups in CDs...

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