Chemoselectivity and Functional Group Compatibility

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. 

The synthetic potential of alkenylzirconium complexes is partially due to the fact that the hydrozirconation of alkynes can be carried out in the presence of some synthetically useful functional groups such as halide [80,153, 211, 212], acetals, amides, imides, carbamates, sulfides [186], ester, cyano [95, 213] and chiral propargyl amino functionalities [214]. 

Enones and enoates undergo 1,2-reduction [115, 191]. Lipshutz et al. reported the effective protection of carbonyl functions by the triisopropylsilyl acyl silane group (TIPS), which allowed the selective conversion of alkenes or alkynes to the corresponding zirconocene complexes [24]. The aldehyde could subsequently be regenerated by desilylation with TBAF [186]. 

As described in the previous section for unsaturated functional groups, Schwartz s reagent (1) and most zirconocene(IV) hydrides readily deprotonate acidic moieties [183, 218]. 

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Building from Krause s study with allenes,it was discovered that Au(l) catalysts can effect intermolecular hydrothiolation of unactivated olefins (32) [12]. 2-Mer-captoethanol reacts exclusively with sulfur, demonstrating chemoselectivity and functional group compatibility. As with the other systems, both aliphatic and aromatic thiols work well. 

Asymmetric hydrosilylation of 2-phenyl-1-butene yields enantiomeric excess ee) values as high as 68% [149]. Products obtained by sequential cyclization/ silylation reactions of 1,5-dienes and 1,6-dienes feature in the suggested mechanistic scenario (Scheme 8) [149, 155]. Furthermore, hydrosilylation of terminal olefins achieved both excellent chemoselectivity in the presence of any internal olefin, and functional-group compatibility with halides, ethers, and acetals [155]. 

The CuI-TTTA catalyst system exhibits excellent functional group compatibility, and 5-iodotriazoles are obtained as exclusive products in excellent yield from structurally and functionally diverse azides and 1-iodoalkynes. Due to the mild reaction conditions, high chemoselectivity, and low copper catalyst loading, reaction work-up is usually as simple as trituration followed by filtration. The scale-up is easy, and a number of 5-iodotriazoles have been prepared in multigram quantities. 

Nitrile hydratases (NHases) catalyze the hydration of organic nitriles to amides under very benign reaction conditions (neutral aqueous environment and room temperature) and therefore offer a chemoselective alternative to classical approaches, where functional group compatibility is often limited due to the harsh acidic or basic solutions used [1], Starting with their application in acrylamide production [2,3], this enzyme class is one of the most prominent in industrial processes with respect to production volume (>3 X 10 kg/a for acrylonitrile hydration) [4]. Hence, Lonza (Switzerland) uses a nitrile hydratase to convert 3-cyanopyridine into nicotinamide (6 X 10 tons/year). Very recently, a one-pot industrial protocol for the synthesis of a chiral intermediate for dlastatin was published that employed a nitrile hydratease/amidase approach [5],... 

Glycopeptides contain many functional groups of different reactivity as well as O- and /V-glycosidic bonds. Therefore, the compatibility and chemoselectivity of the applied reactions is a fundamental prerequisite in glycopeptide synthesis. In this chapter, efficient and generally applicable methods and their combinations will be illustrated by examples [5,8,91. 

Chemoselectivity, high yields and compatibility of reactive functional groups with the reaction conditions are noteworthy features. 

The chemoselective oxidation of a saturated secondary alcohol in the presence of a saturated primary alcohol is possible with a number of reagents. N-Bromosuccinimide in an aqueous organic solvent has been used to carry out this type of selective oxidation and has found use in synthesis. The value of this reagent is exemplified by its use in the synthesis of isocyanopupukeanane and in work towards a total synthesis of gelsemine (equations (32) and (33) respectively). Clearly this reagent would not be compatible with all functional groups, given the well-known reactivity of N-bromosuccinimide towards unsaturated compounds. 

Although the polymerization prowess of organolanthanide complexes has been known for some time, efforts to apply these catalysts to small molecule synthesis have only recently begun. The selectivity of these metallocenes is predominantly steric in nature, and they are compatible with a wide variety of organic functional groups. A review of their use in olefin hydrogenation,hydrosilylation, and polyene cydization with emphasis on chemoselectivity and diastereoselectivity is presented here. The various ways in which the catalysts and reagents can be tuned to produce the desired products is also discussed. 

Radical methods are of central importance in organic synthesis [1], These reactions are performed under mild and neutral conditions, which usually avoids competing ionic side reactions. Carbon-centered radicals are compatible with a range of functional groups (e.g. aliphatic alcohols, amines, ketones, esters) and also show high chemoselectivity under carefully controlled reaction conditions. Furthermore, reactions involving loss of stereochemistry at the non-radical center are not problematic, and hence radical methods are emerging as a powerful synthetic tool in the field of carbohydrate chemistry. 

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