Reactions with triflates

2 Cross-coupling of Organoboron Compounds with Organic Halides 

The order of reactivity of halides and triflates for the cross-coupling reaction of boron reagents is I Br OTf Cl. Thus, the sequential cross-coupling reaction of haloaryl 

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After extensive experimentation, a simple solution for avoiding catalyst deactivation was discovered, when testing an Ir-PHOX catalyst with tetrakis[3,5-bis (trifluoromethyl)phenyl]borate (BArp ) as counterion [5]. Iridium complexes with this bulky, apolar, and extremely weakly coordinating anion [18] did not suffer from deactivation, and full conversion could be routinely obtained with catalyst loadings as low as 0.02 mol% [19]. In addition, the BArp salts proved to be much less sensitive to moisture than the corresponding hexafluorophosphates. Tetrakis (pentafluorophenyl)borate and tetrakis(perfluoro-tert-butoxy)aluminate were equally effective with very high turnover frequency, whereas catalysts with hexafluorophosphate and tetrafluoroborate gave only low conversion while reactions with triflate were completely ineffective (Fig. 1). 

The key compounds in the synthesis of 4,4 -dithiocello- and -xylotrioses are the per-acetylated 1,4-dithiodisaccharides (43 a, 43 b) (Scheme 14) which are obtained from acylated (39 a, 39 b) by hydrogen bromide treatment and displacement of the halide by potassium or tetrabutylammonium thioacetate. Total deacetylation of the donors and reaction with triflated acceptors (34 a) or (34b) afforded the expected trisaccharides which can be converted after conventional treatment, into free trisaccharides (44d,44e,44g and 44 h) [40]. Using the same stepwise procedure, but with activation of the donor by selective in situ S-de-acetylation and activation, the cellotetraoside (44 i) and cellopentaoside (44j) were obtained in good yield [41]. 

So far the reactivity of epoxides has involved their use as an electrophile. However, oxtranyl anions can serve as functionalized nucleophiles in their own right. Thus, the sulfonyl substituted epoxide 107 can be deprotonated with -butyllithium to provide a stabilized anion which engages in facile Sn2 reaction with triflate 108 <03JOC9050>. Other examples of such stabilized epoxide anions include those derived from oxazolinyloxiranes (e.g., 110), which react with nitrones to provide the spirotricyclic heterocycles of type 112, Hydrolysis provides the epoxy amino acids 113, in which the carboxylic acid moiety was provided by the oxazoline nucleus and the amine functionality was derived from the nitrone <03OL2723>. A recent report has demonstrated that oxiranyl anions can also be stabilized by the amide functionality <03H(59)137>. 

Related Reagents. Optically active trisubstituted sulfonyl-stabilized oxiranyllithiums can be generated by deprotonation of the corresponding epoxy sulfones (eq 9). Due to the diminished reactivity of the reagents by steric hindrance, the reaction with triflates requires HMPA to obtain a high yield of product (eq 10). ... 

Ready availability of cycloalkenyl triflates from ketone precursors often renders them superior to the corresponding halides in synthesis. The syntheses of arylated cycloalkenes [164] and 2-substituted carbapenems (Scheme 2-59) [165] have been achieved in excellent yields by the reaction with triflates. 

An interesting and efficient method of converting dimethyl (5)-malate (2) to dimethyl (i )-malate (203) uses dimethylformamide as the nucleophile in an Sn2 reaction with triflate 197a [71]. The displacement is rapid, and is complete within 15 min at room temperature. The intermediate formate 202 can either be isolated and purified prior to conversion to 203, or... 

The tetracyclic A/B/C/D ring core of (205)-camptothecin, one of the most potent antitumor natural products isolated from Camptotheca acuminate, was prepared by a combined directed ortho metallation/cross-coupling strategy. Snieckus showed that 2-bromo-6-methoxypyridine (152) could be sequentially treated with ter/-butyllithium (2 equiv) at -78 °C and anhydrous zinc bromide. The resulting organozinc species was then subjected to palladium-catalyzed cross-coupling reaction with triflate 153 to afford the biaryl 154, a precursor to the tetracyclic A/B/C/D ring core 155. 

Thioglycosides can be activated for gfycosylation reactions with sulfur electrophiles, e.g., with dimethyl(methylthio)sulfonium triflate or with methanesulfenyi bromide and silver(l +) to form reactive sulfonium intermediates (F. Dasgupta, 1988). 

For coupling, the cheaper aryl fluorosulfonate 713 is used as an alternative to the expensive aryl triflates to give the same results[473]. The arenesulfonates 714 are active for the reaction with vinylstannanes when dppp and LiCI are used in DMSO[583], The bromide 715 attacks the arylstannane moiety selectively without reacting with the organoboron moiety in 716 in the absence of a base[584]. 

Although the Lewis acids used as co-reagents in Friedel-Crafts acylations are often referred to as catalysts, they are, in fact, consumed in the reaction, with the generation of strong acids. There has been considerable interest in finding materials which could function as true catalysts. Considerable success has been achieved using lanthanide triflates. ... 

Skraup/Doebner-von Miller-type reactions with lanthanide catalysts under microwave radiation are efficient for a variety of different anilines. For example, cyclisation of aniline 44 with acetone in the presence of scandium triflate gave the desired product 45 in excellent yield. 

Compound 40 has not yet been synthesized. However, there is a large body of synthetic data for nucleophilic substitution reactions with derivatives of 41 [synthesized from aliphatic and aromatic aldehydes, pyridine, and trimethylsilyl triflate (92S577)]. All of these experimental results reveal that the exclusive preference of pathway b is the most important feature of 41 (and also presumably of 40). 

Besides a polymerization of the Michael acceptor, a double alkylation of the starting ketone, by reaction with a second Michael acceptor molecule, may take place as a side reaction, and thus further reduce the yield. The polymerization of the enone 2 as well as the double alkylation of the starting ketone can be avoided by application of a modern procedure for the Robinson annulation that uses an organotin triflate as catalyst." ... 

The boronic acid 2 is first converted to an activated species 8 containing a tetravalent boron center by reaction with a base. Halides or triflates (OTf = trilluoromethanesulfonate) are used as coupling partners R-X for the boronic acids. In many cases the rate-limiting step is the oxidative addition. With respect to the leaving group X, the rate decreases in the order ... 

Larhed et al. investigated enantioselective Heck reactions with 2,3-dihydrofuran as alkene [86]. In the coupling with phenyl triflate, conditions previously reported by Pfaltz [87] were attempted under microwave irradiation. Interestingly, the catalytic system Pd2(dba)3/(4S)-4-t-butyl-2-[2-(diphenylphosphanyl)phenyl]-4,5-dihydro-l,3-oxazole, identified by the Swiss team, was found suitable for high-temperature microwave-assisted enantioselective Heck reactions (Scheme 76). Using a proton sponge as a base and benzene as a solvent gave the best conversions (Scheme 76). At tempera-... 

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