Chemoselectivity additions

Once a molecule is modified with a hydrazine reagent and another molecule is modified with the benzaldehyde compound, they may be combined to form the final conjugate, which will result in a hydrazone linkage between the two molecules. In addition, chemoselective ligation using aldehyde/hydrazine reactions may be done to immobilize biomolecules. In this regard, one modified component may be a surface and the other one an antibody, protein, or oligonucleotide destined for immobilization onto the surface. 

High CO partial pressure promotes the formation of unmodified cobalt catalyst [211,212]. Using a 50% excess of syngas (Fig. 23B), a reduced activity was observed. The conversion decreased from 96% (run a ) to 12.2% (rim d ) after four runs. In addition, chemoselectivity decreased considerably. Both hydrogenation, particularly to octane, and isomerization increased. 

Investigation of this phenomenon led to the finding that not only is the azide addition chemoselective, it is also regioselective, as indicated by the isolation of the bisadduct 8, and not 9 or 10 (Fig. 5). The preparation of bisazafulleroid compounds has been patented [38]. 

The same catalyst system works well in hetero-allylic asymmetric alkylations (h-AAA Scheme 1-16). Substrates such as enol esters 163 provide entry to nonracemic esters of allylic alcohols. Remarkably, competing 1,2-addition and/or acyl transfer were not issues yields are good (80-99%). In these cases, catalyst loading can go as low as 0.8%, and ee s are mostly >95%. Additional chemoselectivity has been noted in the case of cinnamyl ester 163, where the desired Sn2 AAA takes place without competing Cu-catalyzed 1,4-addition to the enoate. This sets the stage for a subsequent metathesis (GH-2 = Grubbs-Hoveyda second-generation catalyst) en route to butenolide 164. 

Chemoselectivity in the cycloaddition of 2-methylenecycloheptenone (174) changes on addition of In(acac)3. The allylic carbonate 175 reacts with the ketone 174 in the presence of In(acac)3 to give the methylenetetrahydrofuran 176, and the methylenecyclopentane 177 is obtained in its absence[l 13], The cycloaddition of ynones to produce the methylenetetrahydrofuran proceeds smoothly only in the presence of In(acac)3 (10 mol%)[114]. 

Addition to Carbonyl Compounds. Unlike Grignard and alkykitliium compounds, trialkylboranes are inert to carbonyl compounds. The air-catalyzed addition to formaldehyde is exceptional (373). Alkylborates are more reactive and can transfer alkyl groups to acyl halides. The reaction provides a highly chemoselective method for the synthesis of ketones (374). 

Epoxides are regio- and stereoselectively transformed into fluorohydrins by silicon tetrafluoride m the presence of a Lewis base, such as diisopropyleth-ylamme and, m certain instances, water or tetrabutylammonium fluoride The reactions proceed under very mild conditions (0 to 20 C in 1,2-diohloroethane or diethyl ether) and are highly chemoselective alkenes, ethers, long-chain internal oxiranes, and carbon-silicon bonds remain intact The stereochemical outcome of the epoxide ring opening with silicon tetrafluoride depends on an additive used, without addition of water or a quaternary ammonium fluoride, as fluorohydrins are formed, whereas m the presence of these additives, only anti opening leading to trans isomers is observed [17, 18] (Table 2)... 

Me- SiCl also affects the stereoselectivity of 1,2-additions to carbonyl compounds [ 133]. Witli the aid of suitable activators, these mildly reactive reagents show selec-tivities unattainable by the conventional reagents, as ilustrated below for Me- SiCl-dependent Chemoselectivity fEq. 10.13) [134]. 

A stereochemical issue of great importance presents itself here. In the chemoselective reduction of the two ketone carbonyls at C-5 and C-8 in 6, the addition of hydride takes place on the same side... 

BVMOs were also reported to facilitate mild and chemoselective conversion of boronic acids to borates, which usually hydrolyze upon biotransformation conditions using isolates protein [217]. Additionally selenium oxidation has been described in analogy to sulfoxidations [218]. 

This 1,4-dlfunctlonalised compound cannot easily be made from diketone (24) because of the chemoselectivity problem. The o-halo ketone (25) is a better starting material and this could be made by HBr addition to (26). 

This is nearly a Diels-Alder adduct and removal of the extra CHg group gives a Dlels-Alder adduct (2). The reaction must be chemoselective addition of CH2N2 to one carbonyl group only of (2). This is most easily achieved from the anhydride (3). 

Until recently, iron-catalyzed hydrogenation reactions of alkenes and alkynes required high pressure of hydrogen (250-300 atm) and high temperature (around 200°C) [21-23], which were unacceptable for industrial processes [24, 25]. In addition, these reactions showed low or no chemoselectivity presumably due to the harsh reaction conditions. Therefore, modifications of the iron catalysts were desired. 

The complexes [Cu(NHC)(MeCN)][BF ], NHC = IPr, SIPr, IMes, catalyse the diboration of styrene with (Bcat) in high conversions (5 mol%, THF, rt or reflux). The (BcaO /styrene ratio has also an important effect on chemoselectivity (mono-versus di-substituted borylated species). Use of equimolecular ratios or excess of BCcat) results in the diborylated product, while higher alkene B(cat)j ratios lead selectively to mono-borylated species. Alkynes (phenylacetylene, diphenylacety-lene) are converted selectively (90-95%) to the c/x-di-borylated products under the same conditions. The mechanism of the reaction possibly involves a-bond metathetical reactions, but no oxidative addition at the copper. This mechanistic model was supported by DFT calculations [68]. 

Hydroarylation, (addition of H-Ar, Ar = aryl), of alkynes, catalysed by Pd(OOCCH3)2 or Pd(OOCCFj)j in acetic acid, is an atom-economic reaction, giving rise to substituted c/i-stilbenes (Fujiwara reaction). Catalytic conversions and improved chemoselectivity to the mono-coupled product under mild conditions can be achieved by modification of the metal coordination sphere with NHC ligands. Hydroarylation of mesitylene by ethylpropiolate (Scheme 2.19) catalysed by complex 107 (Fig. 2.18) proceeds in good conversions (80-99%, 1 mol%) under mild conditions at room temperature. 

The 1,4-addition of ZnEt2 to 2-cyclohexenone was also performed by these workers in the presence of thioether-phosphite D-xylose-derived ligands, depicted in Scheme 2.11. In all cases, the chemoselectivities in the 1,4-product were higher than 97% but the enantioselectivities were modest (<41% ee). It was noted that changing the substituent in the thioether moiety produced an elfect on both the reactivity and the enantioselectivity, as shown in Scheme 2.11. 

An arenethiolatocopper (I) complex has been used by van Koten et al. to catalyse the 1,4-Michael addition of Grignard reagents to acyclic enones, providing the corresponding products with excellent chemoselectivities, high... 

---