Multifunctionalized synthesis

Synthesis of camptothecin (163) is another example[133]. The iboga alkaloid analog 164 has been synthesized smoothly by the intramolecular coupling of iodoindole and unsaturated ester to form an eight-membered ring. Af-Methyl protection of the indole is important for a smooth reaction[134]. An efficient construction of the multifunctionalized skeleton 165 of congeners of FR900482 has been achieved[135]. 

Carboxylic acids are produced in water. Selection of solvents is crucial and the carbonylation of the enol triflate 480 can be carried out in aqueous DMF, and that of the aryl triflate 481 in aqueous DMSO using dppf as a ligand[328,334]. The carbonylation of the enol triflate 482 to form the a, 0. unsaturated acid 483 using dppf as a ligand in aqueous DMF has been applied in the total synthesis of multifunctionalized glycinueclepin[335]. 

In conclusion, there is interest for bioethanol upgrading to fuel additives and some research is active in this direction, but much more effort is needed to demonstrate the validity and the viability of the concept of preparing oxygenated diesel fuel additives from bioethanol and glycerol. The key to success is to develop selective multifunctional solid catalysts, in which interest is more general, because similar multifunctionality is necessary in the catalytic synthesis of fine chemicals [67]. There is, thus, the possibility of cross-fertilization between the two research areas. 

Another approach for the synthesis of networks relies on the polycondensation of multifunctionalized polyesters with the appropriate multifunctionalized agent, provided that one of the partner is at least tri-functionalized. Toward this end, several reaction have been reported, such as the Michael addition of amines onto acrylates [184], the coupling of ketones and oxyamines [185], the click copper(II)-catalyzed azide-alkyne cycloaddition [186], and esterification reactions [25, 159, 187]. Interestingly, if esterification reactions are used, the crosslinks are then degradable. 

While the early examples of this cyclocondensation process typically involved a / -ketoester, aromatic aldehyde and urea, the scope of this heterocycle synthesis has now been extended considerably by variation of all three building blocks, allowing access to a large number of multifunctionalized pyrimidine derivatives. For this particular heterocyclic scaffold the acronym DHPM has been adopted in the literature and is also used throughout this chapter. Owing to the importance of multi-component reactions in combinatorial chemistry there has been renewed interest in the Biginelli reaction, and the number of publications and patents describing... 

Our interest in expanding the acylative pyrrole annulation approach to additional heterocyclic systems has led to an efficient synthesis of pyrrolo[3,2-c]pyridin-2-ones and pyrido[3,4-6]pyrrolizidin-l-ones starting from 4-chloro-N-benzyl-2(l//)-pyridinone and amino acid salts.811 Over the years pyrrolo[3,2-c]pyridines (5-azaindoles)41 have been of interest for applications as elements in new drug design, nucleotide analogues,42 and biochemical tools. However, available synthetic routes to multifunctionalized members from this class of heterocyclic structures are limited.41 43... 

The high diastereoselective synthesis of multifunctionalized 3,4-dihydro-coumarins bearing a quaternary stereocenter was developed through tandem Michael additions of indole and its derivatives (1-methyl, 2-methyl, 4-methoxy, 5-methoxy, 5-bromo, 6-benzyloxy) to 3-nitrocoumarines (3-nitro-chromen-2-one, 6- and 7-methyl-3-nitro-chromen-2-one) followed by methyl vinyl ketone in a one-pot step. For the tandem Michael additions, after the first Michael reaction of indole (2) with 3-nitrocoumarine (51) catalyzed... 

In conclusion, it is obvious that A-heterocyclic carbenes and their unique, but concurrently versatile reactivity have already proven wide applicability. The offered catalytic (and enantioselective) access to important reactive intermediates such as homoenolates or enolates as well as their additional catalytic properties will smooth the way for mild and sustainable synthesis of multifunctionalized compounds. 

In order to make use of the (potential) multifunctionality of cyclopropenes (cf. Fig. 1) in synthesis, their reactivities have to be tuned. All efforts to achieve this goal finally focussed on the use of transition metal catalysts. Before we discuss the various transition metal catalyzed reactions of cyclopropenes in detail, we will briefly summarize their stoichiometric reactions with transition metal complexes (Scheme 1). These may be regarded as equivalents of important elementary steps in a catalytic cycle. Four different types of reactions have been observed. Reactions at the double bond involve... 

As outlined in Scheme 10.23, this catalytic strategy could be applied for the synthesis of multifunctionalized cyclohexanes 18 and cyclopentanes 19 with two quaternary stereocenters in excellent enantioselectivities (up to >99% ee) and high diastereoselectivities (93 7-99 1). 

Figure 2.66 Multifunctionality of solid catalysts synthesis of maleic anhydride from n-butane over a (V0)2P207 catalyst.

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