Hindered aryl

PD—S) to yield phosphates and alcohols, see Scheme 5 reaction a. Sterically hindered aryl phosphites (e.g., AO 14) have an additional chain breaking activity, i.e. they react with peroxyl and alkoxyl radicals during their function as antioxidants (reactions 5b and 5c) [18]. 

Such cyclohexadienes are easily oxidizable to benzenes (often by atmospheric oxygen), so this reaction becomes a method of alkylating and arylating suitably substituted (usually hindered) aryl ketones. A similar reaction has been reported for aromatic nitro compounds where 1,3,5-trinitrobenzene reacts with excess methyl-magnesium halide to give 2,4,6-trinitro-l,3,5-trimethylcyclohexane. Both... 

However, modification of the allyl fragment by substitution of one of the terminus positions has provided more active complexes by enabling a more facile activation step [159], This allows the coupling of highly hindered amines with hindered aryl chlorides at room temperature and with low catalyst loadings [160] (Scheme 6.48). 

Entry 2 shows an E-enolate of a hindered ester reacting with an aldehyde having both an a-methyl and (3-methoxy group. The reaction shows a 13 1 preference for the Felkin approach product (3,4-syn) and is controlled by the steric effect of the a-methyl substituent. Another example of steric control with an ester enolate is found in a step in the synthesis of (-t-)-discodermolide.99 The E-enolate of a hindered aryl ester was generated using LiTMP and LiBr. Reaction through a Felkin TS resulted in syn diastereoselectivity for the hydroxy and ester groups at the new bond. 

Palladium complexes of inexpensive, easily synthesized bis(phosphinite) PCP -pincer ligands show good activity in the Suzuki coupling of deactivated and sterically hindered aryl bromides.256... 

Generally, monophosphine complexes can be generated by decomposition of suitable precursors, among which the most notable are palladacycles (Section 9.6.3.4.7). A spectacular example makes use of spontaneous disproportionation of a dimeric complex of Pd1 with very bulky ligands to give one of the most reactive catalytic systems known so far, which catalyzes the fast crosscoupling of arylboronic acids with aryl chlorides and hindered aryl bromides at room temperature (Equation (28)) 389... 

Simple dialkylgermanethiones are stable only at very low temperatures. A stable diaryl-germanethione (31) was synthesized with stongly sterically hindered aryl groups 11, as shown in reaction 14. The diarylgermanethione 31 is a solid crystalline compound, stable at room temperature. However, it undergoes addition reactions across the Ge=S double... 

Catalytic asymmetric cyanide addition to imines constitutes an important C—C bondforming reaction, as the product amino nitriles may be converted to non-proteogenic a-amino acids. Kobayashi and co-workers have developed two different versions of the Zr-catalyzed amino nitrile synthesis [73]. The first variant is summarized in Scheme 6.22. The bimetallic complex 65, formed from two molecules of 6-Br-binol and one molecule of 2-Br-binol in the presence of two molecules of Zr(OtBu)4 and N-methylimidazole, was proposed as the active catalytic species. This hypothesis was based on various NMR studies more rigorous kinetic data are not as yet available. Nonetheless, as depicted in Scheme 6.22, reaction of o-hydroxyl imine 66 with 5 mol% 65 and 1—1.5 equiv. Bu3SnCN (CH2C12, —45 °C) leads to the formation of amino nitrile 67 with 91 % ee and in 92 % isolated yield. As is also shown in Scheme 6.22, electron-withdrawing (— 68) and electron-rich (—> 69), as well as more sterically hindered aryl substituents (— 70) readily undergo asymmetric cyanide addition. 

Ligand 19 was found to be highly selective for the hydrogenation of 1-aryl, I -alkyl alkenes, and ligand 18b was found to be selective for 1-aryl, I -hindered aryl alkenes (Table 7). 

The O-methylated extract was derivatized with 99 percent C-enriched methyl iodide. The NMR spectrum of the extract showed a strong absorption at 56 ppm (relative to TMS), which can be attributed to unhindered aryl methyl ethers (67%), a smaller absorption at 60 ppm, attributable to hindered aryl methyl ethers (23%), and a resonance at 51 ppm, assignable to methyl esters derived from carboxylic acids (10%).(16) TTiese results are consistant with those of Liotta l al, who studied the alkylation of whole Illinois No. 6 coal.(12)... 

The sugar conversion and the monoethers/polyethers ratio (mono/poly ratio) were determined at 75°C for 140 min, using [Pd(acac)2/3PPh3] as the catalytic system with a sugar/butadiene/Pd ratio = 150 900 1 in DMF [28, 29]. Under these conditions, the conversions of 15 and 16 were 31 and 39% respectively with mono/ poly ratio = 5.2 and 8.1. Interestingly, the addition of triethylamine (20 equiv./Pd) increased the conversion and the selectivity towards the monoethers 51 and 56% conversions with mono/poly ratios = 9 and 19 for 15 and 16, respectively (Table 4). The conversion is also sensitive to the nature of the phosphane and to the Pd/ phosphane ratio. Indeed, variation of only the phosphane leads to conversions varying from less than 2 to 99%, alkyl phosphanes and sterically hindered aryl phosphanes being less effective. The selectivity also depends on the phosphane (Table 4) [29]. 

Figure 1.1 Examples of temperature dependences of rate constants for the reactions in which the low-temperature rate constant limit has been observed 1, hydrogen transfer in excited singlet state of molecule (6.14) 2, molecular reorientation in methane crystal 3, internal rotation of CH3 group in radical (7.42) 4, inversion of oxyranyl radical (8.18) 5, hydrogen transfer in the excited triplet state of molecule (6.20) 6, isomerization in the excited triplet state of molecule (6.22) 7, tautomerization in the ground state of 7-azoindole dimer (6.15) 8, polymerization of formaldehyde 9, limiting stage of chain (a) hydrobromi-nation, (b) chlorination, and (c) bromination of ethylene 10, isomerization of sterically hindered aryl radical (6.44) 11, abstraction of a hydrogen atom by methyl radical from a methanol matrix in reaction (6.41) 12, radical pair isomerization in dimethylglyoxime crystal (Figure 6.25).

Non-Arrhenius behavior of the isomerization rate constant of sterically hindered aryl radicals 2,4,6-triterbutylphenyl... 

Chaumeil, H. Signorella, S. Le Drian, C. Suzuki cross-coupling reaction of sterically hindered aryl boronates with 3-iodo-4-meth-oxybenzoic add methyl ester. Tetrahedron 2000, 56, 9655-9662. 

Griffiths, C. Leadbeater, N. E. Palladium and Ni-catalyzed Suzuki cross-coupling of sterically hindered aryl bromides with PhB(OH)2. Tetrahedron Lett. 2000, 43, 2487—2490. 

When IBioxl2 HOTf was employed as the ligand precursor for the Suzuki-Miyaura coupling of sterically hindered aryl chlorides and aryl boronic acids, excellent to good yields were obtained in refluxing toluene for a variety of starting materials (Table 6). Notably, this work represents the first report of tetra-orf/zo-substitulcd biaryl compounds achieved from aryl chlorides [143]. 

Three applications of this reaction are possible (1) isomerization of sterically hindered aryl radicals, (2) enol-keto transformation, and (3) sigmatropic hydrogen shift. 

Organomagnesium compounds add to unsubstituted arenes only under forcing or Barbier conditions [1], On the other hand, aromatic rings substituted by electron-withdrawing groups are surprisingly susceptible to attack by organomagnesium compounds. The early work on reactions of hindered aryl ketones [2] has been little further developed [3], despite some reports which should surely be followed up, e.g. [4],... 

Methoxy-2,6-dimethylbiphenyl [BHT, LiCI, and CuBr as additives for a hindered aryl triflate and aryltin] [54]. 

Aminophosphine 4 is an excellent supporting ligand in the room-temperature reaction of aryl bromides and primary amines [42]. The 4/Pd-catalyst is capable of coupling a hindered aryl bromide such as 2-bromo-raefa-xylene with -butylamine in excellent yield, Eq. (76). 

Ketones can also be obtained by treatment of the lithium salt of a carboxylic acid with an alkyllithium reagent (16-28). For an indirect way to convert carboxylic esters to ketones, see 16-82. A similar reaction with hindered aryl carboxylic acids has been reported. " Treatment of a p-amido acid with two equivalents of M-butyllithium, followed by reaction with an acid chloride leads to a p-keto amide.Carboxylic acids can be treated with 2-chloro-4,6-dimethoxy[l,3,5]-triazine and the RMgX/Cul to give ketones. " ... 

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