Intermolecular regiocontrol

I.3.4.2. Intermolecular Cycloaddition at C=X or X=Y Bonds Cycloaddition reactions of nitrile oxides to double bonds containing heteroatoms are well documented. In particular, there are several reviews concerning problems both of general (289) and individual aspects. They cover reactions of nitrile oxides with cumulene structures (290), stereo- and regiocontrol of 1,3-dipolar cycloadditions of imines and nitrile oxides by metal ions (291), cycloaddition reactions of o-benzoquinones (292, 293) and aromatic seleno aldehydes as dipolarophiles in reactions with nitrile oxides (294). 

Intermolecular Hydrosilylation of Internal Alkynes 10.17.3.5.1 Yttrium catalysts for regiocontrol based on sterics... 

Concerning the regiocontrol of intermolecular Pauson cyclization in which a homo-allylic donor group is present in the alkene subunit [195], there seems to be some electronic contributions. 

Intermolecular cyclopropanation of 2-substituted terminal diene 121 with rhodium or copper catalysts occurs preferentially at the more electron-rich double bond (equation 109)37162. With a palladium catalyst, considerable differences in regiocontrol can occur, depending on the substituent of the diene. In general, palladium catalysed cyclopropanation occurs preferentially at the less substituted double bond (equation 110). However, with a stronger electron-donating substituent present in the diene, e.g. as in 2-methoxy-l, 3-butadiene, the catalytic process results in exclusive cyclopropanation at the unsubstituted double bond (equation 110)162. 

Steric factors, in some cases, are the key to the regiocontrol in intermolecular cyclopropanation reactions. The inertness of trisubstituted double bonds to palladium catalysed cyclopropanation may explain the extremely regoselective cyclopropanation observed with FK 506 (equation 10)20. 

The inclusion of a separate chapter on catalysed cyclopropanation in this latest volume of the series is indicative of the very high level of activity in the area of metal catalysed reactions of diazo compounds. Excellent, reproducible catalytic systems, based mainly on rhodium, copper or palladium, are now readily available for cyclopropanation of a wide variety of alkenes. Both intermolecular and intramolecular reactions have been explored extensively in the synthesis of novel cyclopropanes including natural products. Major advances have been made in both regiocontrol and stereocontrol, the latter leading to the growing use of chiral catalysts for producing enantiopure cyclopropane derivatives. 

Donor/acceptor-substituted carbenoids are usually much more chemoselective than the more established carbenoids functionalized solely with acceptor groups [lc]. The development of these donor/acceptor-substituted carbenoids has enabled enantioselective intermolecular C-H insertions to become a very practical process. These carbenoids have a strong preference for functionalizing C-H bonds where positive charge build-up at C in the transition state is favored but these electronic effects are counter-balanced by steric factors. Benzylic and allylic sites and C-H bonds adjacent to oxygen and nitrogen functionality are favored but these sites can also be sterically protected if desired. By appropriate consideration of the regiocontrolling elements, effective intermolecular C-H insertions at methyl, methylene, and methine sites have been achieved. 

If the all-carbon tether is replaced by a connection which may be removed after reaction, then the IMDA can be used to construct six-membered rings with high levels of stereo- and regiocontrol, which would otherwise be impossible or very difficult to prepare using the analogous intermolecular reaction. A wide variety of tethering systems have been examined and proved to be successful in the formation of highly functionalized cyclohexanes. 

The importance of the tether in enabling such high stereo- and regiocontrol was further exemplified upon investigation of the analogous intermolecular reaction [6 a, d]. Exposing silyl ethers 6 (diene) and 7 (dienophile) to similar reaction conditions provided a mixture of all four possible regio- and stereoisomers in the ratio 3 2 2 1 (Scheme 10-2). 

Alternative approaches that have been explored for control of photochemical reactions include irradiation in liquid crystals [7], micelles [8], inclusion complexes [9], and zeolites [10]. In addition, photochemistry of monolayers [11] and on surfaces [12] (e.g., alumina, silica, clays, and semiconductors) has received considerable attention. Each of these methods has potential for regiocontrol and/or stereocontrol of certain photochemical processes. However, reactions between different groups (e.g., intermolecular photocycloadditions) are difficult to modulate with most of these approaches. 

M 10. Krafft, M.E. Regiocontrol in the Intermolecular Cobalt-Catalyzed Olefin-Acetylene Cycloaddition J. Am. Chem. Soc. 1988,110, 968-970... 

Regiocontrol is a major challenge in intermolecular Mizoroki-Heck reactions, and usually results in a mixture of Unear and branched products (cf. Section 1.2.2.3 on directed Mizoroki-Heck chemistry). Both, Cabri et al. [14] and Hayashi et al. [15] showed that the nature of the ancillary Ugand L has a pronounced effect on the regioselectivity when palladium is Ugated by bidentate phosphines (Scheme... 

Coordination assemblies also show unique properties and functions through their architectures. Coordination cage 5 shows the stereo- and regiocontrol of intermolecular [2- -2] photodimerizations of olefins as well as the acceleration of the reactions (Figure 18a and This result means... 

An efficient route to quinazolinones was reported by Willis et al. They described the palladium-catalyzed coupling of o-bromobenzoate esters such as 50 with monosubsti-tuted ureas (Scheme 24.25) [100]. The reactions proceeded via initial intermolecular C—N bond formation followed by intramolecular base-promoted cyclization to yield the 3-alkylated quinazolinedione products in good yields. Complete regiocontrol was observed, which originates from the initial aryl C—Nbond formation occurring at the least hindered N-atom of the urea nucleophile. 

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