Variation of the aryl group

New compounds derived from MPEP and MTEP are numerous, and the SAR directions can be generally divided into three strategies (a) variation of the aryl groups and their substituents, (b) replacement of the alkyne linker, and (c) fusion of the alkyne linker to one of the two aryl groups. Much of this work has been reported... 

In a related study, the Shibasaki group examined cyclizadon of naphthyl triflate 10.1 (Scheme 8G.10) [23], Cyclization of 10.1 under standard cationic conditions gave Heck product 10.2 in 78% yield and 87% ee. Evidently, the reaction is fairly tolerant of the nature of the aryl group, because both 10.1 and 9.3 behaved similarly. An interesting variation of this reaction was also demonstrated in which Suzuki coupling and asymmetric Heck cyclization were performed in a one-pot operation. Thus, treatment of ditriflate 10.3 with borane 10.4 under standard Heck conditions provided 10.2 in similar enantioselectivity to the stepwise procedure, albeit in quite low yield. Heck product 10.2 was converted in several steps to the natural products, halenaqui-none (10.5) and halenaquinol (10.6). 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

Sharpless oxidation of the oxazole 52 provides an intermediate epoxide, which is attacked by the neighboring amino group, eventually leading to the pyrrolo[2,3-r/ isoxazole 53 (Equation 12). Variation of the aryl substituent provided access to a set of related derivatives in excellent yields <2006TL4957>. 

Experimental observations of the aziridination of styrene-type alkenes, catalyzed by CuPF6 in the presence of chiral diimine ligands (such as (lR,2R,A i4A i4)-A A -bis(2,6-dichlorobenzylidene)cyclohexane-l,2-diamine 425), have been taken as evidence of the intermediacy of a discrete, monomeric Cu(lll)-nitrene complex, (diimine)Cu=NTs 423. Variation of the steric properties of the aryl group in the oxidant TsN=IAr (Ar = Ph, 2-/-Bu, 5,6-Me3C6H) has no effect on the enantioselectivities in forming the aziridination products 424 (Scheme 108) <1995JA5889>. 

At present, we are studying the optimal conditions for the displacement reactions by using different solvents, temperatures, and acids. We have found that variation in the aryl groups also increases the selectivity of dearylation. For example, the p-methoxyphenyl group is displaced by triflic acid much more rapidly than the unsubstituted phenyl ring. 

Subtle alterations to sterics and electronics of the aryl group as in catalysts 63-65 (Figure 22) were generally well tolerated, but only led to minor differences in overall metathesis activity and Z-selectivity [43], Catalyst 66, which contains an V-DIPP substituent, was an obvious target, given the improved Z-selectivity observed in the case of the six-membered chelate (50). However, initial attempts to prepare 66 or other catalysts with significant variation of electronic and steric parameters were hampered by the instability of the products under the reaction conditions, which used silver pivalate. 

With alkyl aryl ketones, it is the aryl group that generally migrates to the nitrogen, except when the alkyl group is bulky. The reaction has been applied to a few aldehydes, but rarely. With aldehydes the product is usually the nitrile (16-21). Even with ketones, conversion to the nitrile is often a side reaction, especially with the type of ketone that gives 17-31. A useful variation of the Schmidt reaction treats a cyclic ketone with an alkyl azide (RN3) in the presence of TiCU, generating a... 

Ru—C(carbene) bond distances are shorter than Ru—P bond lengths, but this can simply be explained by the difference in covalent radii between P and The variation of Ru—C(carbene) bond distances among ruthenium carbene complexes illustrates that nucleophilic carbene ligands are better donors when alkyl, instead of aryl, groups are present, with the exception of 6. This anomaly can be explained on the basis of large steric demands of the adamantyl groups on the imidazole framework which hinder the carbene lone pair overlap with metal orbitals. Comparison of the Ru—C(carbene) bond distances among the aryl-substituted carbenes show... 

Another important variation of the Staudinger ligation reaction described above involves the use of cleavable aryl groups on the triphenylphosphine component, which allows for... 

The use of cyclic alkenes as substrates or the preparation of cyclic structures in the Heck reaction allows an asymmetric variation of the Heck reaction. An example of an intermolecular process is the addition of arenes to 1,2-dihydro furan using BINAP as the ligand, reported by Hayashi [23], Since the addition of palladium-aryl occurs in a syn fashion to a cyclic compound, the 13-hydride elimination cannot take place at the carbon that carries the phenyl group just added (carbon 1), and therefore it takes place at the carbon atom at the other side of palladium (carbon 3). The normal Heck products would not be chiral because an alkene is formed at the position where the aryl group is added. A side-reaction that occurs is the isomerisation of the alkene. Figure 13.20 illustrates this, omitting catalyst details and isomerisation products. 

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