Functional group compatibility

Ethers and halogens do not interfer in hydrozirconation. However zirconium hydrides can reduce several types of carbonyl groups to alcohols. Nitriles are reduced to aldehydes. Consequently, these functions have to be protected. 

The low valent Zr species prepared by reduction of ZrCl4 with Na amalgam in the presence of a 1,3-diene and of a phosphine are highly efficient catalysts for the reduction of mono and disubstituted olefins and acetylenes to the corresponding alkanes. The same species also catalyze the metathesis of 1,3-cyclohexadiene into cyclohexane and benzene [49], a reaction that is also very efficiently achieved with cobalt-based Ziegler-type catalysts [50]. 

Laboratoire de Chimie Macromolecutaire et de Catalyse Organique, and Laboratoire de Synthese Organique et de Catalyse, 

Me Quillin, Homogeneous Hydrogenation in Organic Chemistry, D. Reidel (1976) C. Master, Homogeneous Transition-Metal Catalysis, Chapman and Hall (1981). 

Hayashi, K. Kabeta, I. Hamachi and M. Kumada, Tetrah. Lett., 2865 (1983). 

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The generality and functional group compatibility were also excellent with regard to the alkynes (Table 2). Free hydroxyl groups and even a remote double bond were compatible and give very good yields and purities. 

The Stille reaction has developed as a popular protocol for the formation of C-C bonds due to the air- and moisture-stability as well as functional group compatibility of organotin compounds. Together with the Suzuki-Miyaura coupling it is one of the most powerful methods for the synthesis of molecules containing unsymmetrical biaryl moieties. However, despite its efficiency, this versatile reaction has slowly been displaced by other procedures that avoid the use of highly toxic organostannanes. 

The chemoselectivity of Schwartz s reagent (1) toward alkynes, alkenes, nitriles, and carbonyl groups, and thus its general functional group compatibility, can be modulated. However, it is important to keep in mind that the presence of functional groups may have regiochemical consequences on the hydrozirconation reaction. 

Scheme 20 Mechanism, functional group compatibility, and selectivity within enyne cy-clizations catalyzed by 70 Cy = cyclohexyl...

Scheme 22 Functional group compatibility and diastereoselectivity within diene cycliza-...

Six-membered rings were formed in good to excellent yields via cycli-zation of 1,7-dienes 107 and 109 when the reaction was performed in 1,2-dichloroethane at room temperature (Scheme 23) [65]. Similar functional group compatibility and olefin substitution tolerance was observed as found... 

The palladium-catalyzed reductive coupling reactions were used in the synthesis of several natural products, including laurene [75], ceratopicanol [80], and dihydrostreptazolin 141 [81]. The cyclization leading to dihydrostrepta-zolin shown in Eq. 26 highlights the diastereoselectivity and functional group compatibility seen with this catalytic system. 

The range of functional groups compatible with the molybdenum initiators includes fluoroalk-yls, esters, acetals and maleimides.531,532 However, protic functionalities such as alcohols and acids are not tolerated, and aldehydes terminate the polymerization. 

In conclusion, the ene reaction has undergone a synthetic renaissance with the advent of Lewis acid and transition metal-catalyzed protocols. The carbonyl-ene, imino-ene, and Alder-ene reactions have all experienced tremendous growth due to the mild conditions in which these reactions can be performed, the high functional group compatibility and high stereoselectivity. As a confirmation of the synthetic utility of the ene reaction, there are many applications to natural product synthesis, and some of these are highlighted in Section 10.12.6. Finally, it should be mentioned that these catalyzed ene reactions are still in their infancy, so much remains to be learned. 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

In addition to the examples laid out in the above schemes, the sulfoxide method has been employed in the synthesis of numerous natural products. The examples presented below are chosen to illustrate the power of the method and the broad functional group compatibility. 

As evidenced by the plethora of reviews cited in the preceding paragraphs, certain substrates and transition metals that affect the intra- and intermolecular Alder-ene reaction have been extensively studied. However, new ways to attain this synthetically useful reaction are valuable since some of these processes are completely substrate-dependent and involve metal catalysts with low functional group compatibility. This chapter details the role of rhodium(I) catalysts in achieving the formal Alder-ene reaction. 

Enhanced reaction rates, improved yields, and high functional group compatibility are the features demonstrated by these ionic liquids. The products are weakly soluble in the ionic phase, so that they are easily separated by simple extraction with ether. 

These syntheses provide further examples of the efficient nucleophilic displacement of halide from ot-halo boronic esters, even by very hindered strong bases, as well as the functional group compatibility of the synthesis. 

For a survey of functional group compatibility in olefin metathesis, refer to Armstrong, S. K. /. Chem. Soc., Perkin Trans. 1 1998, 54, 371-388. 

Subsequently, direct incorporation of GO by titanocene(ii) catalyst, Gp2Ti(GO)2, under a GO atmosphere was reported.This catalytic system showed substantially higher TON and broader functional group compatibility. However, this catalyst fails to react with sterically hindered olefins and alkynes. In a recent contribution from the same group, a series of aryloxide titanium complexes 22 (figure 4) are prepared and shown to promote PKR with some sterically hindered enynes." ... 

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