Palladium-catalyzed glycosylations

Feringa and coworkers [258] and O Doherty et al. [259] independently reported palladium-catalyzed glycosylations of 2-substituted 6-acyl-2H-pyran-3(6H)-one derivatives and alcohols (Scheme 5.98). This reaction presumably involves electrophilic Pd 7t-allyl complex intermediate, which was generated by the reaction of 2-substituted 6-acyl-2Ff-pyran-3(6H)-one and Pd(0)/PPh3. It is noteworthy that 2-substituted 6-acyl-2H-pyran-3(6H)-one derivatives were stereoselectively converted into 2-substituted 6 - a I k o x y - 2 H - p y r an - 3 (6 H) -o n e derivatives with complete retention of configuration by this reaction. A two-step reduction/oxidation manipulation after the glycosylation can install new stereocenters in the obtained glycosides. 

H. Guo and G. A. O Doherty, De novo asymmetric synthesis of the anthrax tetrasaccharide by a palladium-catalyzed glycosylation reaction, Angew. Chem., Int. Ed., 46 (2007) 5206-5208. 

In an effort to address the medicinal chemist s need for new synthetic methods for the preparation of unnatural carbohydrates, new de novo methods for carbohydrate synthesis have been developed. These routes use asymmetric catalysis to set the sugar absolute stereochemistry, a palladium-catalyzed glycosylation reaction to stereoselectively control the anomeric center, and subsequent diastereoselective post-glycosylation to install the remaining sugar stereocenters. The utility of this method has been demonstrated by the syntheses of several classes of mono-, di- and tri-saccharides. 

This de novo approach to carbohydrates has also been applied to oligosaccharides (Schemes 9 to 14). Key to the success of this approach is the development of a mild palladium-catalyzed glycosylation (Scheme 6) in combination with the use of the previously developed highly stereoselective enone reduction and dihydroxylation reaction (Scheme 3) as post-glycosylation transformation for the installation of manno stereochemistry 19). 

This reaction has great potential for the preparation of various D- and L-sugars in either the a- or P-configuration. For instance, we have found that nitrogen nucleophiles like 6-chloro-9//-purine 8.1 also work well in this palladium-catalyzed glycosylation (8.1 8.2 to 8.3). This can be seen in our... 

Scheme 7 Liu and coworkers iterative palladium-catalyzed glycosylation approach to trisaccharide 21.

Another approach involving the palladium-catalyzed glycosylation was developed by O Doherty et al. The glycosylation of the pyranone substrate 170, which was obtained from 2-acyl furan 165 in 3 steps, with a glycosyl-acceptor 171 in the presence of a 2.5mol% Pd catalyst and 10mol% PhsP smoothly proceeded to provide the a-glycoside 172 in excellent yield as a... 

SCHEME 38.38. De novo synthetic approach using the palladium-catalyzed glycosylation of a pyranone substrate. 

Bahu RS, Zhou M, O Doherty GA. De novo synthesis of oh-gosaccharides using a palladium-catalyzed glycosylation reaction. J. Am. Chem. Soc. 2004 126 3428-3429. 

Zhou M, O Doherty GA. A Stereoselective synthesis of digi-toxin and digitoxigen mono- and bisdigitoxoside from digi-toxigenin via a palladium-catalyzed glycosylation. Org. Lett. 2006 8 4339-4342. 

Sulfonylated glycals are also useful precursors of 1-unsaturated C-glycosyl compounds. For example, treatment of 52 with an excess of tri-n-butyltin hydride in the presence of a free radical initiator (AIBN) in refluxing toluene leads to exchange of the anomeric sulfonyl group resulting in 1-stannyl glycal 53, which in turn can be coupled with bromoaryl substrates in a palladium-catalyzed reaction to 54 (O Scheme 17) [153]. 

Palladium-catalyzed arylation and vinylation of alkene is referred to as the Mizoroki-Heck reaction and is one of the most widely used Pd(0)-catalyzed C-C bond formations in organic synthesis. However, the reaction has not been extensively employed for C-glycosylation [96]. The example shown in O Scheme 67 outlines the reaction of iodopyridine and furanose gly-cal for the synthesis of C-nucleoside [97]. The mechanism began with the oxidative addition of iodopyridine to Pd(0) catalyst, and the resulting organo-palladium species was inserted by... 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

P. De Shong, M. E. Mowery, E. D. Soli, A. S. Manoso, M. C. Patterson, C. J. Handy, and M. -R. Brescia, Transmetalation in palladium-catalyzed cross-coupling and Staudinger imination reaction of glycosyl acceptors using hypervalent silane and siloxane derivatives, US Patent, US 6,414, 173 B1 (July 2, 2002) Chem. Abstr., 137 (2002) 63421. 

In a series of recent contributions, Liu and coworkers have evaluated the potential of the palladium-catalyzed decarbo)q lative reaction in the synthesis of allylic glycosyl derivatives. In this context, they described a palladium-catalyzed stereo- and regioselective C-glycosylation process based on an intramolecular decarboiq lative coupling. Initial studies with glycal derived p-ketoesters, e.g. 4, allowed the authors to identify... 

Scheme 2 Liu and coworkers stereoselective palladium-catalyzed decarboxylative C-glycosylation leading to p-C-glycosyl derivatives 6.

Scheme 5 Palladium-catalyzed O-glycosylation of glycal carbonates 11 leading to disaccharides 12.

O-Picoloyl glycal derivative 22 has also been successfully used as the glycosyl donor on a palladium-catalyzed allylation reaction with various N-heterocyclic nucleophiles leading to p-ALglycosyl derivatives type 28, (Scheme 11). ... 

Scheme 9 Palladium-catalyzed O-glycosylation of alcohols and phenols with 22, leading to p- or a-glycosides, 27 and 24, respectively.

Scheme 10 Palladium-catalyzed O-glycosylation of alcohols and phenols with CZ-epi-22.

Scheme 11 Palladium-catalyzed A/-glycosylation of N-heterocycles with C-3-O-picoloyl D-glycal 22, leading to p-A/-glycosyl derivatives 28, in a stereoselective manner.

---