Chemoselective control

In Heading 1.4 we have already seen that three different kinds of control elements [3] may be considered 1) chemoselective control elements (controlling chemical reactivity), 2) regioselective control elements (controlling the orientation of reactants) and 3) stereoselective control elements (controlling the spatial arrangement of atoms within the molecule), which may control either the relative (diastereoselective) or the absolute spatial arrangement (enantioselective control elements). 

Chemoselective control elements protecting and activating groups. Latent functional groups... 

Sometimes, instead of using protecting groups as chemoselective control elements it may be more convenient to resort to activating groups as, for instance, the S-2-pyridylcarboxylic esters (24) which react intramolecularly to give macrolides 25 in excellent yields [20] (Scheme 12.7). 

Introduction Chemo-, Regio-, and Stereoselectivity Chemoselectivity Controlling Chemoselectivity Regioselectivity Markovnikov Hydration Mercuration-reduction Wacker oxidation... 

The reactivity of phosphonate carbanions towards five- or six-membered alkenones (354) with a hetero group Z has been shown to be chemoselectively controlled by the nature of the group Z. When Z = Cl, reaction affords the compounds (355) and these, when acted upon by acidic reagents (Scheme 17) undergo dehydration leading to (356) or (357). Exceptionally, 3-chlorocyclopen-tenone leads to (363). When Z = OMe, the initial reaction leads to (358) (R, R = H or Me), and both this type of intermediate, and the already recorded... 

A special merit of this host-type is that the inclusion cavity disposed is easily to tune to the geometric and steric requirements of the guest enclosure by altering the bulk of the side arms. However, guest inclusion showing a distinct specifity against different classes of compounds, i.e. chemoselectivity control, are not feasible on a desirable scale. 

Figure 1. Chemoselectivity Control in Reactions with Nucleophilic Products.

Amemiya [28] has reported the use of electrochemical flow allylation, between allylic halides (33) and aldehydes (34) (Scheme 6.12) where in batch it is incredibly difficult to control whether the y-adduct (3S) or a-adduct (36) is obtained. The authors report that by altering the order of reagent addition and cathode material, chemoselective control over product formation can be achieved. Pt and Ag worked... 

Stille and Heck reaction can be combined using multifunctional substrates such as the halotriflates in Scheme 5-203. By careful optimization of the reaction conditions, a chemoselective control of the one-pot Stille-Heck reactions and Heck-Stille reactions is enabled. For example, as de Meijere and co-woikers have shown, cyclohexadienes are accessible by a sequential (not one-pot) reaction of vinyl stannanes (Stille) and... 

The chemoselective desilylation of one of the two different silyi enoi ethers in 10 to give the monosilyl enol ether II is realized by the Pd-catalyzed reaction of Bu3SnF. The chemoselectivity is controlled by steric congestion and the relative amount of the reagent[7,8]. An interesting transformation of the 6-alkoxy-2,3-dihydro-6//-pyran-3-one 12 into the cyclopentenone derivative 13 proceeds smoothly with catalysis by Pd(OAc)2 (10 mol%)[9]. 

In a similar way, enetetraynes can undergo a pentacyclization as observed for compound 6/1-272, which gave 6/1-273 in 66% yield (Scheme 6/1.72). In this case the initial alkenyl-Pd-species is formed by an oxidative addition of Pd° to the alkenyliodide moiety in 6/1-272 [130]. In comparison to the reaction of6/1-270, this procedure has the advantage of complete control of the chemoselective formation of the alkenyl-Pd-species, but the disadvantage that the starting material is less easily accessible. 

Radicals are versatile synthetic intermediates. One of the efficient procedures for radical generation is based on one-electron oxidation or reduction with transition metal compounds. An important feature is that the redox activity of transition metal compounds can be controlled by appropriate ligands, in order to attain chemoselectivity in the generation of radicals. The application to small ring compounds provides useful methods for organic syntheses. Reductive transformation are first reviewed here. 

The tendency of nitrones to react with radicals has been widely used in new synthetic routes to well-defined polymers with low polydispersity. The recent progress in controlled radical polymerization (CRP), mainly nitroxide-mediated polymerization (NMP) (695), is based on the direct transformation of nitrones to nitroxides and alkoxyamines in the polymerization medium (696, 697). In polymer chemistry, NMP has become popular as a method for preparing living polymers (698) under mild, chemoselective conditions with good control over both, the polydispersity and molecular weight. 

Controlled single-stage carbometallation reactions of alkenes and alkynes with group 4—7 metals are discussed with emphasis on regio-, stereo-, and chemoselectivity including clarification and understanding of factors governing these synthetically important aspects. 

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