Chemoselective activation

Iridium hydride complexes effectively catalyze addition of nitriles or 1,3-dicarbonyl compounds (pronucleophiles) to the C=N triple bonds of nitriles to afford enamines.42S,42Sa Highly chemoselective activation of both the a-C-H bonds and the C=N triple bonds of nitriles has been observed (Equation (72)). To activate simple alkane dinitriles, IrHs(P1Pr3)2 has proved to be more effective (Equation (73)). The reaction likely proceeds through oxidative addition of the a-C-H bonds of pronucleophiles to iridium followed by selective insertion of the CN triple bonds to the Ir-C bond. 

Glycosyl esters with remote functionality constitute a relatively new class of O-carbonyl glycosyl donors, which fulfill the prospect of mild and chemoselective activation protocols (Scheme 3.22). For example, Kobayashi and coworkers have developed a 2-pyridine carboxylate glycosyl donor 134 (Y = 2-pyridyl), which is activated by the coordination of metal Lewis acid (El+) to the Lewis basic pyridine nitrogen atom and ester carbonyl oxygen atom [324]. In the event, 2-pyridyl (carbonyl) donor 134 and the monosaccharide acceptor were treated with copper(II) triflate (2.2 equiv) in diethyl ether at —50 °C, providing the disaccharide 136 in 70% (a P,... 

A direct enantioselective cross-aldol-type reaction of acetonitrile with an aldehyde (RCHO) has been reported, giving /3-cyano alcohol product, R-CH (OH)-CH2-CN, (7e) in up to 77% ee.148 CH3CN, acting as an acetate surrogate, is chemoselectively activated and deprotonated using a soft metal alkoxide (CuO-Bu1) in a strong donor solvent (HMPA), with a bulky chiral diphosphine as auxiliary. 

Besides conformational disarming, one-pot methods also benefit from building blocks that are electronically disarmed. Biao Yu and coworkers utilized this effect in the one-pot assembly of the 19-membered macrolactone-containing tricolorin A (16) (Scheme 6.3) [13, 14], The key design of their synthesis is the chemoselective activation and coupling of the perbenzylated donor 7 to the bis-acyl-containing disarmed bifunctional acceptor 12. The subsequent glycosylation of macrolactone 14 in the same flask formed the protected tricolorin A15 in 43% overall yield, which was deprotected to provide tricolorin A (16). 

SCHEME 6.11 Kobayashi s one-pot synthesis of trisaccharide 63 through chemoselective activation of glycosyl iV-trichloroacetylcarbamate. 

One-Pot Glycosylation Based on Chemoselective Activation of Different Types of Glycosyl Donors... 

SCHEME 6.14 One-pot glycosylation based on chemoselective activation of different types of glycosyl donors. 

A number of one-pot syntheses that rely on mixed conventions,191,219 for instance selective and chemoselective activations, as well as acceptor-187,220 and bidirectional strategy-based approaches221,222 have also been developed. These techniques offer further advantages for the synthesis of longer or branched oligosaccharide sequences. 

M. N. Kamat and A. V. Demchenko, Revisiting the armed-disarmed concept rationale Chemoselective activation of the S-benzoxazolyl glycosides in oligosaccharide synthesis, Org. Lett., 7 (2005) 3215-3218. 

An example of this strategy is illustrated in Scheme 3, which describes the synthesis of a positional isomer of sialyl Lewis. Eor instance, armed glycosyl donor phenyl 2-thio-a-sialoside 11 was chemoselectively activated with NlS/TfOH in the... 

Murahashi described a new pyrrole synthesis involving a rhodium complex-catalyzed reaction of isonitriles (e.g., 3) with 13-dicarbonyl compounds 4 to afford the pyrroles 5 <01OL421>. This process is believed to proceed by chemoselective activation of the a-C-H bond of the isonitrile even in the presence of the more acidic dicarbonyl derivative. 

There are two digressions. The first describes a convergent strategy to multiple contiguous chiral centers which involves aldol condensation of two sugars. The second reports a procedure for chemoselective activation of the anomeric oxygen. 

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