Regiospecific process

The displacement of a ligand L from the phosphorus atom of a phosphoranyl radical can easily occur via a-scission of the L-P bond (Scheme 23). The fragmentation is a regiospecific process, i.e., the leaving group must be apical (Scheme 23) and it occurs via an intermediate o" structure (Fig. 5). 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

The addition reaction of alcohols to silenes is a strictly regiospecific process the OR group in the product is always attached to the silicon. The reaction is of special importance since silenes are easily trapped by reagents like methanol and t-butanol, and isolation of the adducts is normally taken as evidence for an intermediate silene. Furthermore, the alcohol addition to silenes is the prototypical reaction for the 1,2-addition of polar bonds across the Si=C double bond. A complete account on the alcohol addition to silenes, including the most recent mechanistic implications, is given in the chapter by Sakurai. We will therefore give only a brief survey of the reactivity of several families of silenes towards alcohols. 

In thiepanes 89, 90, and 92, transannular attack at C3 or C4 could lead to a mixture of polyhydroxylated tetrahy-drothiopyrans or tetrahydrothiophenes. However, by the reaction of substrates 89 (or 90) and 92 with Me3SiI, 91 and 93 were obtained exclusively (free of any five-membered cyclic sulfides), respectively, through a seven- to six-membered ring-contraction reaction. In both cases, as predicted for an Sn2 transannular cyclization and due to the presence of a -symmetric axis (Scheme 11), only one diastereoisomer was obtained. Episulfonium salt was proposed to be formed by a stereo- and regiospecific process, followed by a ring contraction toward the more stable tetrahydrothiopyran derivative. 

Some other nitrogen compounds are also formed by carbamoylation of glycals using a photochemical regiospecific process which consists of the addition of the amide radical only to C-l [53]. The addition mixture remains complex because of stereoisomers 54 (mainly a) and competitive addition products with acetone such as 55. 

With dissymmetrical alkynes or alkenes, very clean reactions are often obtained by regiospecific processes see Regioselectivity) For example, the use of phosphorus unsaturated reagents afford the opportunity to generate various mono or diphosphanes and related species (Scheme 29). ... 

But the different substituent at C -1 and C - 5 has shown, two routes (a) and (b). However the reaction proceeds via the path (a) only and gives 1, l-dimethyl-2, 2-diphenyl-3 (2, 2-dimethyl) vinyl cyclopropane. This regiospecific process results from cleavage of the three membered ring of diradical towards the isopropyl radical [path (a)] rather than the more stable diphenyl methyl radical [path (b)]. 

The Lewis acid-catalyzed cyclization of 3-anaino-2-alkerLirnines (21) leads to a wide variety of alkyl- and aryl-substituted quinolines (59). The high regiospecificity and the excellent yields obtained make this process promising. 

Since /V-acylation is a reversible process, it has allowed the regiospecific alkylation of, for example, imidazoles to give the sterically less favored derivative. This principle is illustrated in Scheme 7 (80AHC(27)24l). 

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

Rhodium-catalysed addition (10) of hydridosilanes (Chapter 17) to a/3-unsaturated carbonyl compounds can be performed regioselectively, to afford either the product of 1,2-addition, or, perhaps more usefully, that of 1,4-addition, i.e. the corresponding silyl enol ether this latter process is an excellent method for the regiospecific generation of silyl enol ethers. Of all catalyst systems investigated, tris(triphenylphosphine)rhodium(l) chloride proved to be the best. 

Free-radical addition of Se-phenyl areneselenosulfonates to acetylenes is also a facile process, occurring regiospecifically and stereoselectively to afford the E-isomer of a -(phenylseleno) vinyl sulfone (26) in high yield88. 

The base-catalyzed Michael addition of 2-chlorocyanoacetate to a,p-unsaturated ketones or aldehydes affords 5-oxopentenenitrile derivatives. In the presence of anhydrous HCl, these compounds cyclize to yield 2-chloro-3-pyridinecarboxylates. The process is highly regiospecific and usefiil in the synthesis of 2,Xdisubstituted pyridines <95T(51)13177>. 

The fact that from the ionized ester 46 mainly QHj is eliminated whereas the stereoisomeric compound 47 decomposes preferentially via CH3 loss24 is best explained23 by the operation of a two-step process (12). The regiospecific hydrogen transfer 46->48 is responsible for C2H5 loss, whereas CH3 is likely to be eliminated from the intermediate 50. It should be mentioned that the different reactivities of the... 

Aromatic fluorination can be carried out by a regiospecific destannylation process shown in reaction 69. This is an effective method for producing fluorinated m-tyrosine and other radiopharmaceuticals, as shown in reaction 70. The process can be applied for radiolabelling with 18F, denoted as F in these reactions, and the products used as radioactive tracers for clinical and fundamental investigations318-321. 

The regiospecific functionalization of the terminal alkyl group of simple amines or ethers with bis(pinacolato)-diborane leads to organoboranes. The latter have manifold applications in organic synthesis since the catalytic borylation process can be combined with a functional group transformation step, including Suzuki-Miyaura couplings, for the synthesis of elaborated molecules. Curiously, functionalization of the C-H atoms a to the heteroatom was not observed (Equation (22)). a... 

The allylic cation (40), formed in a specific acid-catalysed process, is relatively stable thermodynamically, stable enough towards trapping by nucleophiles that the reaction product obtained is almost invariably the naphthalene elimination product. di-Enediynes (42) are formed regiospecifically when the allylic cation (41) is trapped as shown. The walking of methanol around optically active l-methyl-3-ethylallyl... 

Aminosugars are the result of replacement of one or more hydroxyl groups in a sugar by amino groups. They are formed in nature by transamination processes (see Section 15.6) on appropriate keto sugars, which are themselves the product of regiospecific... 

---