Alkylation chemoselectivity

Mono-N-substituted alkanesulfonamides react with 2 equiv. of n-butyllithium or LDA generating the corresponding dilithium salts which can then be alkylated chemoselectively on the carbon atom. ... 

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... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Alkylation of purine derivative 72 yields an N-7/N-9 regioisomer (73/ 74) mixture which can be purified using aluminium oxide/H+ to provide the N-9 isomer selectively as a parallel or chemoselective high-throughput purification <00TL3573>. 

Fluorochromenes result from the reaction of the Cs salts of salicylaldehydes with the phosphonium triflate 37 (Scheme 24) <0OJCS(Pl)103> and 3-acylchromenes are formed from salicylaldehydes and alkyl vinyl ketones in a chemoselective Baylis-Hillman reaction (Scheme 25) . 

Selective alkylation of ketonesThis reagent forms a complex so much more rapidly with aldehydes than with ketones that selective alkylation of a keto group in the presence of an aldehyde group with an alkyllithium or Grignard reagent is possible. The opposite chemoselectivity is achieved with the bulky methylaluminum bis(2,6-di-f-butyl-4-phenoxide) (MAD, 13, 203 this volume). 

Allylic alkylation (cf., 12,557). This W(0) complex in combination with 2,2 -bipyridyl (bpy) catalyzes reactions of nucleophiles with allylic acetates or carbonates, but the chemoselectivity is complementary to that of Pd(0), as shown in equation (I). The W(0)-catalyzed reactions are influenced by inductive and steric... 

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