Chemoselective functionalization

Such a methodology is also useful for the chemoselective functionalization of internal voids of dendrimers. This can be accomplished for example by adding 2 equiv. of allyl, propargyl or phosphonate trifluoromethane sulfonate on the dendrimer of generation 1 71-lGj] (Scheme 34). Functionalization occurs on the sulfur atom of the two P=N-P(S) units with the quantitative formation of the... 

While a variety of techniques are available for the monoprotection of symmetrical diols, there are few methods that allow for the chemoselective functionalization of the more hindered hydroxyl in an unsymmetrical 1,3-diol.5 The acid-catalyzed reaction of an unsymmetrically substituted cyclic formal with acetyl chloride described here invariably proceeds via preferential rupture of the less congested C(2)-0 bond to give a product having an acetate at the less congested site... 

The authors apphed this new concept to chemoselective functionalization of carbonyls rather than acetals [194], which is usually quite difficult to achieve because of the high reactivity of the acetal counterparts with Lewis acids. Reaction of a mixture of 1 equiv. each of acetophenone and its dimethyl acetal with ketene silyl acetal 191 under the influence of bidentate aluminum Lewis acid 188 in CH2CI2 at -78 °C for 3 h afforded aldol products 195 exclusively (88 % yield). It is worth noting that employment of dibutyltin bis(triflate) (DBTT) (10 mol%) as catalyst [195], which is quite useful for activation of aldehyde carbonyls rather than acetals, gave unsatisfactory results, producing the y3-methoxy ester preferentially (Sch. 147). 

In the Lewis acid-promoted allylation of aldehydes with allyltributyltin, virtually complete chemoselective functionalization of aldehyde carbonyls is also observable and the opposite chemoselectivity is easily accessible by use of TiCU as promoter, as shown in Sch. 148 [106],... 

Chemoselective Function(iUz.ution of Different Carbonyl Group... 

MAPH is another possibility available for the chemoselective functionalization of ketones (Scheme 2-12) [12]. The alkylation involved in mode F3 is almost inoperative because the aldehydic carbon is steiically, i.e., kinetically, deactivated by the cooperation of the MAPH ligands, thereby presumably forming a sort of sandwich stmcture (1-4). The reaction rate of RLi (R Bu, Ph, etc.) with ketones consequently becomes faster. 

Table 2-4. Chemoselective functionalization between two different aldehydes with ATPH. ...

Table 2-6. Chemoselective functionalization of two different conjugated aldehydes.

Table 2-7. Chemoselective functionalization of carbonyls over acetals or ketals.

Table 2-8. Chemoselective functionalization of carbonyls over acetals. Entry Nucleophile (Nu ) Products yield (ratio)...

Aluminum tris(2,6-diplienylphenoxide) (ATPH), an aluminum-based Lewis acid with bulky substituents, is valuable as an extremely selective activator of less hindered aldehyde carbonyls (Scheme 10.8) [36]. In competitive aldol reactions of two different aldehydes, more fhan one equivalent of ATPH achieves highly chemoselective functionalization of less hindered aldehydes. Unfortunately, catalytic use of ATPH reduces the chemical yield and chemoselectivity. In contrast, a catalytic quantity of aluminum bis(trifluoromethanesulfonyl)amide 13 can promote the chemoselective aldol reaction. 

This unusual stabilization effect of MAPH has been successfully utilized for discrimination between two structurally different aldehyde carbonyls, thereby allowing the chemoselective functionalization of sterically more hindered aldehydes [44]. 

In 2013, Law and McErlean demonstrated the intramolecular vinylogous Stetter reaction as a new addition to the collection of NHC-catalyzed transformations. The products of this new transformation possess multiple sites for chemoselective functionalization, including (but not limited to) ketones, esters, and alkenes. Utilizing chiral triazolium salts as the NHC catalyst precursor, aromatic aldehydes or aliphatic aldehydes proceeded with various heteroatom tethered vinylogous Michael acceptors to give five- and sk-membered rings (up to 88% yield, 96% ee) (Scheme 7.20). 

Zhang reported a Au(I)-catalyzed diastereo- and enantioselective domino cycHzation/[3+3] cycloaddition of 2-(l-aIkynyl)-2-alken-l-one 216 with nitrone 217, affording the corresponding chiral heterobicyclic furo[3,4-d][l,2]oxazine 218 [67]. This reaction is attractive by its easy scale-up possibility (gram scale) and the chemoselective functional group transformation in the product (Scheme 11.46). 

Keywords Aldehydes, malononitrile, C-H activated acids, urea, organocatalyst, ethanol-water (1 1), room temperature, tandem Knoevenagel-cyclocondensation, one-pot three-component reaction, chemoselectivity, functionalized 2-amino-3-cyano-4//-pyrans and pyran annulated heterocycles... 

Chemoselective functionalization of 1,6-enynes [124] and 1,4-eneallenes [129] have also been reported. In the former case (equation (65)), only the products resulting from the initial addition of tosyl radical to the alkyne are isolated. 

Scheme 3.12 Chemoselective functionalization of more hindered aldehyde carbonyls with the methylaluminum bis(2,6-diphenylphenoxide/alkyllithium system.

Larre C, Donnadieu B, Caminade AM, Majoral JP (1998) Phosphorus-containing dendrimers chemoselective functionalization of internal layers. J Am Chem Soc 120 4029-4030... 

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