Tertiary alkyl coupling reactions

Moderate yields of acids and ketones can be obtained by paHadium-cataly2ed carbonylation of boronic acids and by carbonylation cross-coupling reactions (272,320,321). In an alternative procedure for the carbonylation reaction, potassium trialkylborohydride ia the presence of a catalytic amount of the free borane is utilized (322). FiaaHy, various tertiary alcohols including hindered and polycycHc stmctures become readily available by oxidation of the organoborane iatermediate produced after migration of three alkyl groups (312,313,323). 

The reaction between nitroxides and carbon-centered radicals occurs at near (but not at) diffusion controlled rates. Rate constants and Arrhenius parameters for coupling of nitroxides and various carbon-centered radicals have been determined.508 311 The rate constants (20 °C) for the reaction of TEMPO with primary, secondary and tertiary alkyl and benzyl radicals are 1.2, 1.0, 0.8 and 0.5x109 M 1 s 1 respectively. The corresponding rate constants for reaction of 115 are slightly higher. If due allowance is made for the afore-mentioned sensitivity to radical structure510 and some dependence on reaction conditions,511 the reaction can be applied as a clock reaction to estimate rate constants for reactions between carbon-centered radicals and monomers504 506"07312 or other substrates.20... 

The reaction between acyl halides and alcohols or phenols is the best general method for the preparation of carboxylic esters. It is believed to proceed by a 8 2 mechanism. As with 10-8, the mechanism can be S l or tetrahedral. Pyridine catalyzes the reaction by the nucleophilic catalysis route (see 10-9). The reaction is of wide scope, and many functional groups do not interfere. A base is frequently added to combine with the HX formed. When aqueous alkali is used, this is called the Schotten-Baumann procedure, but pyridine is also frequently used. Both R and R may be primary, secondary, or tertiary alkyl or aryl. Enolic esters can also be prepared by this method, though C-acylation competes in these cases. In difficult cases, especially with hindered acids or tertiary R, the alkoxide can be used instead of the alcohol. Activated alumina has also been used as a catalyst, for tertiary R. Thallium salts of phenols give very high yields of phenolic esters. Phase-transfer catalysis has been used for hindered phenols. Zinc has been used to couple... 

The ratio ARH/ARj (monoalkylation/dialkylation) should depend principally on the electrophilic capability of RX. Thus it has been shown that in the case of t-butyl halides (due to the chemical and electrochemical stability of t-butyl free radical) the yield of mono alkylation is often good. Naturally, aryl sulphones may also be employed in the role of RX-type compounds. Indeed, the t-butylation of pyrene can be performed when reduced cathodically in the presence of CgHjSOjBu-t. Other alkylation reactions are also possible with sulphones possessing an ArS02 moiety bound to a tertiary carbon. In contrast, coupling reactions via redox catalysis do not occur in a good yield with primary and secondary sulphones. This is probably due to the disappearance of the mediator anion radical due to proton transfer from the acidic sulphone. 

V-alkoxycarbonylamino add (Figure 1.10, path B) did not occur without immediate expulsion of the alkyl group, giving the amino-acid Af-carboxyanhydride (see Section 7.13). 2-Alkoxy-5(47/)-oxazolones are now recognized as intermediates in coupling reactions and are products that are generated by the action of tertiary amines on activated A-alkoxy carbonyl amino adds (see Section 4.16).20 22... 

Free-radical-mediated four-component coupling reactions are rare. However, when an allyltin-mediated radical carbonylation is conducted in the presence of electron-deficient alkenes, four-component coupling reactions take place efficiently to give good yields of p-functionalized <5,fi-unsaturated ketones [40]. The wide scope of this four-component coupling reaction is noteworthy Primary, secondary, and tertiary alkyl bromides and iodides can be used as well as aromatic and vinylic halides. A variety of electron-deficient alkenes, such as methyl vinyl ketone, ethyl acrylate, acrolein, acrylonitrile, and vinyl sulfone, can be used as the acyl radical trap (Scheme 6.23). Fluorous allyltin compounds can also be used in four-component coupling reactions [41]. 

Photoinitiators are generally aryl alkyl ketones or diaryl ketones (Table 2.19). For aryl alkyl ketones two free radicals are produced by homolytic scission of a C-C bond (Eq. (2.96)). Diaryl ketones are usually mixed with a tertiary amine the mechanism of production of free radicals involves H abstraction from the tertiary amine by the excited state PI, via a charge-transfer stabilized exciplex (Eq. (2.97)). The a-amino alkyl radical formed is very reactive and is in fact the true initiator because the cetyl radical disappears rapidly through a coupling reaction (formation of pinacol). 

The iron(III)-mediated oxidative coupling reaction is convenient to perform, because most of the reagents employed are inexpensive and readily available. In general, the yields obtained are sufficient but can be ameliorated when the conversion is performed heterogeneously. Unfortunately, labile moieties represented by secondary or tertiary alkyl, silyl, or iodo substituents will be shifted or lost during the transformation. For the phenolic coupling transformation, hydrated iron(III) salts or complex species, for example K3[Fe(CN)6], can be used. The power of this... 

Fiirstner reported in parallel coupling reactions using 5 mol% of the isolated ferrate(-II) catalyst [Li(TMEDA)]2[Fe(C2H4)4] 4 in THF (Fig. 2) (entry 2) [45, 46], Primary and secondary alkyl bromides and iodides and allylic halides worked well, while alkyl chlorides and tertiary alkyl iodides were inert. Many sensitive functionalities like ester, nitrile, isocyanate, epoxide, and amine groups are tolerated. 

It was recently shown by Zhang and coworkers that Ru(PPh3)3Cl2 is a suitable catalyst for the alkylative coupling of tertiary alcohols 186 to primary alcohols 185 leading to branched alcohols 187 in 32-98% yield (Fig. 46) [258]. The reaction required the presence of a Lewis acid, such as BF3 OEt2. It mediates the dehydration of the tertiary alcohol to a 1,1-disubstituted alkene, which coordinates the ruthenium catalyst. The further course is likely to be similar to the corresponding iron- or rhodium-catalyzed reactions (see Sects. 2.8 and 6). 

Very recently Ryu and coworkers disclosed radical carbonylation/Sonogashira coupling sequences (Fig. 44) [218]. The reaction is applicable to primary, secondary, and tertiary alkyl iodides 177, and terminal aryl or alkyl alkynes 185. Alkynyl... 

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