Strategy 11 Chemoselectivity

Types of reaction N-H bond formation Reaction conditions Water, room temperature Synthetic strategy Chemoselective reduction of nitroaromatics Catalyst Zn dust/NH4Cl/TPGS-750-M (surfactant)... 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

Ballini and coworkers have developed a new strategy for alkenylation of carbonyl compounds based on the Michael addition followed by elimination of HN02 (see Section 7.3). A variety of 2-alkylidene 1,4-dioles have been conveniently prepared, in two steps, by the Michael addition of a nitroalkane to the appropriate enedione derivatives under basic conditions, followed by chemoselective reduction with LiAlH4 (Eq. 4.123).170... 

Four years later, Nelson and Stoddart designed di- and tetra-valent lactosylated dendrons according to a convergent pathway and under mild and chemoselective conditions (Scheme 46).320 The strategy was based on the photochemical addition of hepta-0-acetyl-l-thio-/j-lactose (448) onto bisallyl trisaccharide 449 to form divalent adduct 450. Two nearly quantitative deprotection steps consisting in standard... 

Scientific, Cellomics). For these applications, the use of azide/alkyne reagents in a click chemistry strategy is entirely appropriate and may be the best choice of all conjugation reactions, because of its exquisite chemoselectivity, bioorthogonality, and excellent reaction kinetics. 

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. 

Another efficient strategy, the armed-disarmed approach, developed by Fraser-Reid is based on the chemoselectivity principle [193,202]. According to this... 

Glycosylation Strategies Using Thioglycosides 4.1.6.1 Chemoselective Glycosylations... 

Scheme 4.23 Chemoselective glycosylation by preactivation strategy using Ph2S0/Tf20 promoter.

The concept of armed/disarmed glycosyl donors was subsequently extended by other groups to thioglycosides21 and selenoglycosides.64 A similar strategy has been used by Friesen and Danishefsky to achieve chemoselectivity in electrophilic addition to glycal double bonds.65... 

For the quinone imine cyclization of iron complexes to carbazoles the arylamine is chemoselectively oxidized to a quinone imine before the cyclodehydrogenation [99]. The basic strategy of this approach is demonstrated for the total synthesis of the 3-oxygenated tricyclic carbazole alkaloids 4-deoxycarbazomycin B, hyellazole, carazostatin, and 0-methylcarazostatin (Scheme 17). 

Strategies for functionalization have been developed that exploit the naturally occurring amino acids as well as the non-natural ones. Post-synthetic modifications have been reported that are based on reactive sites that self catalyze the incorporation of the new functionality at the side chains of Lys residues [24,25] and on the chemoselective ligation reaction [26-29]. These developments in combination with new methodology for the synthesis of large proteins [30] provide access to a highly versatile pool of new polypeptides and proteins. 

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