1,2-bifunctionalization

The nucleophilic acylation of aldehydes is a short and efficient pathway to 1,2-bifunctionalized building blocks. This reaction type is extremely valuable, since it allows the catalytic formation of a-hydroxy ketones, which are important synthetic intermediates in organic chemistry. 

Various 1,2-bifunctionalized alkenes containing heteroatoms are prepared by addition to alkynes. Thiophosphorylation of 1-octyne with phosphorothiolate 131 provided (Z)-l-(diphenoxyphosphinyl)-2-(phenylthio)-l-octene in good yield [40]. A useful synthetic method for (Z)-3-phenylthioacrylate derivative is the Pd-catalyzed thioesterification of 1-alkynes with 6)-methyl S-phenyl thiocarbonate (132). Addition of 132 to 1-octyne using Pd(PCy3)2 as a catalyst afforded methyl (Z)-3-phenylthio-2-nonenoate in 86% yield [41]. (Z)-l,2-Bis(phenylthio)alkene was prepared in good yield by stereoselective Pd-catalyzed addition of (PhS)2 (3) to 1-alkyne [2]. 

The bifunctionality of the bis-diene and bis-dienophile monomers is apparent from the condensation product, structure [XXI], which still contains a diene and a dienophile in the same molecule. This polymer is crystalline, indicating a high degree of stereoregularity in the condensed rings. It decomposes to a graphitic material before melting. 

Synthesis of heterocycles on the basis of (3,(3-bifunctionalized ketene N,N-acetals 98UK1013. 

Yamazaki, Kondo and coworkers [78] reported on a combination of a Heck reaction and an animation on solid phase for the synthesis of indole carboxylate 6/1-148, employing an acetylated immobilized enamide 6/1-145 and a bifunctionalized... 

Christov et al. [118-120] have described the synthesis of oxaphosphole derivatives 128 and 130 from bromination of bifunctionalized allenes (Scheme 53). 

Recently, novel bifunctionalized zinc catalysts have been developed (compounds (N) and (P), Scheme 55). They have both Lewis-acid and Lewis-base centers in their complexes, and show remarkable catalytic activity in direct aldol reactions.233-236 A Zn11 chiral diamine complex effectively catalyzes Mannich-type reactions of acylhydrazones in aqueous media to afford the corresponding adducts in high yields and selectivities (Scheme 56).237 This is the first example of catalytic asymmetric Mannich-type reactions in aqueous media, and it is remarkable that this chiral Zn11 complex is stable in aqueous media. 

In the original paper, Eddowes and Hill (1977) had reported that, in addition to 4,4 bipyridine, 1,2 bis(4-pyridyl) ethylene (2) was a more effective promoter of cytochrome c electrochemistry than the 4,4 bipyridine and SSBipy was better than both. This lead Allen and colleagues (1984) to postulate that the prerequirement for successful promoter activity was bifunctionality of the form ... 

Frisbie et al. [120] and Findsay et al. [28] introduced CP-AFM for conductance measurements in (single) molecular junctions. CP-AFM allows precise control of the AFM probe, employing the feedback of the force signal and the simultaneous acquisition of the molecular current response. In order to achieve a better electric contact between the conducting AFM tip and the target molecules of interest, Cui et al. proposed contacting bifunctionalized target molecules embedded in inert... 

Alexandratos, S. D., Natesan, S., Ion-selective polymer-supported reagent principle of bifunctionality, Eur. Polym. J. 35,1999,431-436. 

Several different approaches have been employed in order to build the bifunctionality concept into known dye chromogens. In the case of bis(dichlorotriazine) dyes, which were not exploited commercially, only the arrangement 7.55 is feasible. The difficulty of introducing sufficient extra sulphonic acid groups into the chromogen to compensate for the presence of these two reactive systems and provide adequate solubility and mobility at the low dyeing temperature necessary for such highly reactive molecules proved insuperable. 

Mukerjee, S. and Urian, R.C., Bifunctionality in Pt alloy nanocluster electrocatalysts for enhanced methanol oxidation and CO tolerance in PEM fuel cells electrochemical and in situ synchrotron spectroscopy, Electrochim. Acta, 47, 3219, 2002. 

No by-product is formed. The product has the same elemental composition as that of the monomer. The bifunctionality is provided by the double bond present in the monomer. Compounds containing reactive double bonds can undergo this type of reactions. Typical examples are vinyl compounds (CH2 = CHX),... 

Hydrogels can be made by a number of methods, but one of the most widely used methods is free radical polymerization of vinyl monomers. Examples of vinyl monomers used in our laboratory are shown in Table 1. Monomers are crosslinked with divalent monomers such as A,A -methyl-enebisacrylamide. Biodegradable crosslinking agents can also be used as long as they have bifunctionality. 

A number of different products may be formed, depending on the symmetry of the bifunctionalized building blocks. When at least one of the bifimc-tionalized building blocks is symmetrical, only one structural isomer of the macrocycle is formed. When both are unsymmetrical, head-to-head and head-... 

The steroid may be bifunctionalized with any of the functional groups participating in the Ugi reaction, i.e., isonitrile, amine, aldehyde (ketone), and carboxylic acid, and having two different functionalities on one steroid building block even increases the possibilities. 

A variety of bifunctionalized steroid building blocks were synthesized from the cheap, commercially available lithocholic acid (107, see Fig. 22). 

In addition to this fourfold Ugi macrocyclization using two equivalents of one bifunctionalized steroid building block and another (simpler) bifunc-tionalized building block, two different steroid building blocks can be combined to form a macrocycle in a combined Ugi 5-CR/Ugi 4-CR. For example, diacid 108 and diisonitrile 110, generated by condensation of a steroidal keto-acid with o-(carboxymethyl)-hydroxylamine, react with isobutyraldehyde and isopropylamine to form macrocycle 115 (Scheme 21). 

On the Bifunctionality of Chiral Thiourea Tertiary-Amine Based Organocatalysts Competing Routes to C-C Bond Formation in a Michael-Addition... 

The asymmetric conjugate additions with thiol nucleophiles was further expanded to 2-mercaptobenzaldehydes [98]. Wang had previously developed a domino Michael-aldol reaction promoted by Cinchona alkaloids, and now illustrated the utihty of cyclohexane-diamine bifunctionalized catalysts for the domino... 

The barbiturates were widely used as sedative-hypnotic drugs. Barbital was introduced as a drug in 1903. The method of synthesis for thousands of its analogs has undergone little change. Urea reacts with various derivatives of malonic acid, usually a diethyl ester of a dialkyl substituted malonic acid. This is a classic example of a nucleophilic acyl substitution. A derivative of ammonia reacts with esters to form an amide, only in this case a cyclization to a strainless six-membered ring results because of the proximity of the bifunctionality. 

Figure 6.36 Bifunctionality of cinchona alkaloids (A) and Wynberg s proposal for the transition state of the cinchonidine-catalyzed Michael addition of 4-tert-butylthiophenol to 5,5-dimethyl-2-cyclohexenone (B).

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