Chemoselective alkylation

Isatins can be chemoselectively alkylated at positions 1 or 3. Subsequent reduction of... 

In the laboratory of G.A. Posner, semisynthetic antimalarial trioxanes in the artemisinin family were prepared via an efficient Friedel-Crafts alkylation using a pyranosyi fluoride derived from the natural trioxane lactone artemisinin. The alkylating agent, pyranosyi fluoride, was prepared from the lactone in two steps reduction to the lactol followed by treatment with diethylaminosulfur trifluoride. The highly chemoselective alkylation was promoted by BF3-OEt2 and several electron-rich aromatic and heteroaromatic compounds were alkylated in moderate to high yield using this method. 

Table 2-2. Chemoselective alkylation of a mixture of PhCHO and PhCOMe.

Enantio- and chemoselective alkylations of ketoaldehydes and formylesters using the chiral catalysts DBNE and DPMPM give enantiomerically enriched hy-... 

Despite the low intrinsic reactivity of alkylboranes, Pd-catalyzed all lation with alkylboron compounds holds considerable promise as a unique and chemoselective alkylation method. It is unique in part because hydioboration of alkenes is by far the most general and dependable method for stoichiometrically converting alkenes into organometals and in part because alkylboron compounds thus generated can satisfactorily participate in Pd-catalyzed alkylation under basic conditions. In this connection, it should be noted that the current scopes of hydroalumination and hydiozirconation of alkenes are much more limited than... 

Bhat S, Sridharan V (2012) Iridium catalysed chemoselective alkylation of 2 -aminoacetophenone with primary benzyl type alcohols under microwave conditions. Chem Commiin 48(39) 4701 703... 

Salvatore RN, Smith RA, Nischwitz AK, Gavin T. A mild and highly convenient chemoselective alkylation of thiols using CS2CO3-TBAI. Tetrahedron Lett. 2005 46 8931 8935. 

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

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). 

DIBAL, NiCl2(dppp), toluene, CH2CI2, THF, or ether, 80-97% yield. These conditions are chemoselective for simple alkyl and phenolic allyl ethers. More highly substituted allyl ethers are unreactive. 

This variant gives good to very good yields, and it is chemoselective the primary alkyl halide function in 3 is left unaffected under these reaction conditions. 

Apart from information on stereochemistry, bromine bridging does not provide a priori any rule regarding regio- and chemoselectivity. Therefore, we systematically investigated (ref. 3) these two selectivities in the bromination of ethylenic compounds substituted by a variety of more or less branched alkyl groups (Scheme 4). 

Hydrolysis of both ester groups and chemoselective re-esterification of the more reactive alkyl acid... 

There are several guidelines that should be followed in order to increase the chemoselectivity of the monoadduct. Firstly, radical concentration must be low in order to suppress radical termination reactions (rate constant of activation [fcal and fca2] < < rate constant of deactivation kd t andfcd2]). Secondly, further activation of the monoadduct should be avoided ( al> >kd2). Lastly, formation of oligomers should be suppressed, indicating that the rate of deactivation (kd 2[Cu"LmX]) should be much larger than the rate of propagation ( [alkene]). Alkyl halides for copper-catalyzed ATRA are typically chosen such that if addition occurs, then the newly... 

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