Alkenyl triflates coupling reactions

Although few examples of alkenyl chlorides are involved, the corresponding bromides and iodides are generally useful electrophiles. The cross-coupling of alkenyl iodides is often stereospecific, but that of the bromides sometimes involves ElZ isomerizations due to the required elevated reaction temperatures. The tolerance of alkenyl Inflates has quite enhanced the potential of this protocol as a useful synthetic tool owing to the ready availability of isomerically pure alkenyl triflates. Their reactions usually require the addition of excess LiCl, while it is not necessary when AsPhj and NMP are used as a ligand and a solvent, respectively, as described in SecL Some reactions are shown in Schemes 29-33. 

Heck reaction, palladium-catalyzed cross-coupling reactions between organohalides or triflates with olefins (72JOC2320), can take place inter- or intra-molecularly. It is a powerful carbon-carbon bond forming reaction for the preparation of alkenyl- and aryl-substituted alkenes in which only a catalytic amount of a palladium(O) complex is required. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Tributylstannyl)-3-cyclobutene-1,2-diones and 4-methyl-3-(tributylstan-nyl)-3-cyclobutene-l,2-dione 2-ethylene acetals undergo the palladium/copper-catalyzed cross coupling with acyl halides, and palladium-catalyzed carbon-ylative cross coupling with aryl/heteroaryl iodides [45]. The coupling reaction of alkenyl (phenyl )iodonium triflates is also performed by a palladium/copper catalyst [46],... 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

In addition, aryl triflates have proven to be viable substrates for the Pd-catalyzed Csp2—P bond formation reactions [87-90], Intriguingly, phosphorylation can be achieved from the Pd-catalyzed coupling of alkenyl triflate with not only dialkylphosphites, but also with hypophosphorous acid [88]. Thus, phosphinic acid 87 was obtained when triflate 86 was treated with hypophosphorus acid in the presence of Pd(Ph3P)4. Due to the abundance of alkenyl triflates and milder reaction conditions, alkenyl triflates have certain advantages over the corresponding alkenyl halides as substrates for Pd-catalyzed phosphorylations to make alkenyl phosphonates or phosphinates. 

GRIGNARD-TYPE COUPLING REACTIONS BETWEEN ALKENYL HALIDES (OR TRIFLATES) AND ALDEHYDES, MEDIATED BY THE CrCI2-NiCI2 SYSTEM3... 

The palladium-catalyzed arylation and alkenylation of terminal alkynes with aryl or alkenyl hahdes in presence of a copper(l) co-catalyst is called Sonogashira reaction. In the same way as in the other cross-coupling reactions described before, it is possible to immobihze the alkyne or the aromatic bromides, iodides or triflates on sohd supports (Scheme 3.15). 

Organobismuth compound 1" was also used for the cross-coupling reaction with alkenyl triflates. CC Et-substituted cyclopentenyl triflate afforded the coupling product quantitatively, while the sterically hindered triflate gave the product in poor yield (Scheme 39) [44], Azabismocine 2 reacted with activated alkenyl chlorides to give the coupling products in moderate to good yields (Scheme 40) [54],... 

Scheme 39 Cross-coupling reaction of phenylbismuth alkoxide with alkenyl triflates...

The addition of LiCl and Cul, and triphenylarsine as ligand are required to suppress side-reactions in the carbonylative cross-coupling of geminally substituted alkenyl triflate in the synthesis of sarcodictyin. Stereochemical configuration of the double bond of organotin compound was completely lost in this reaction (Equation (5)). " ... 

Lithium triethyl(l-methylindolyl-2)borate has been introduced as a convenient source of indolyl residue for carbonylative cross-coupling with aryl iodides, alkenyl iodides, or triflates. The reaction requires elevated CO pressure and high loading of catalyst (5mol.%) (Equation (15)). Aryl and alkenyl bromides, as well as aryl iodides... 

Three types of reaction systems have been designed and applied for the enantioposition-selective asymmetric cross-coupling reactions so far. First example is asymmetric induction of planar chirality on chromium-arene complexes [7,8]. T vo chloro-suhstituents in a tricarhonyl("n6-o-dichlorobenzene)chromium are prochiral with respect to the planar chirality of the 7t-arene-metal moiety, thus an enantioposition-selective substitution at one of the two chloro substituents takes place to give a planar chiral monosubstitution product with a minor amount of the disubstitution product. A similar methodology of monosuhstitution can be applicable to the synthesis of axially chiral biaryl molecules from an achiral ditriflate in which the two tri-fluoromethanesulfonyloxy groups are enantiotopic [9-11]. The last example is intramolecular alkylation of alkenyl triflate with one of the enantiotopic alkylboranes, which leads to a chiral cyclic system [12], The structures of the three representative substrates are illustrated in Figure 8F.1. 

TMS group is used for protection of terminal alkynes. However, alkynylsilanes themselves can be used for the coupling with aryl and alkenyl triflates using Pd-CuCl as a catalyst [74], Thus the internal alkyne 160 is prepared by stepwise reactions of two different triflates 157 and 159 with trimethylsilylacetylene (134) via 158. 

Primary alkylboranes derived by hydroboration of terminal alkenes with 9-BBN-H are coupled with aryl and alkenyl triflates and halides under properly selected conditions. The reaction proceeds smoothly without elimination of /1-hydrogen using PdCTklppf) or Pd(Ph3P)4 and K3PO4 in dioxane or DMF [132]. The intramolecular cross-coupling of the alkenyl triflate with the alkylborane in 292, prepared by in situ hydroboration of the double bond in 291 with 9-BBN-H, is applied to the annulation to... 

Optimum conditions for the coupling of the alkenyl triflates 330 with the arylstannanes 331 have been studied. Ligandless Pd complexes such as Pd(dba)2 are most active in the reaction of the enol triflate. PI13P inhibits the reaction. NMP as a polar solvent gives the best results. The use of tri(2-furyl)phosphine and Ph As in the coupling of stannanes with the halides and triflates increases the rate of the transmetallation of the stannanes to Pd, which is thought to be the rate-... 

Terminal alkynes can be alkenylated by alkenyl triflates (bromides, iodides) in the presence of catalytic amounts of a palladium(O) complex (or a precursor thereof) and usually an additional substoichiometric amount of copper(I) iodide (Cul), and they can be arylated by aryl triflates (bromides, iodides). These reactions are called Cacchi coupling reactions if triflate reagents are employed, and Sonogashira-Hagihara coupling reactions if halides are used. 

Although the Heck reaction may be efficiently employed for synthesis, it has its limits that should not go unmentioned the Heck reaction can not—at least not intermolecularly—couple alkenyl triflates (-bromides, -iodides) or aryl triflates (-bromides, -iodides) with metal-free aromatic compounds in the same way as it is possible with the same substrates and metal-free alkenes. The reason is step 4 of the mechanism in Figure 16.35 (part II). If an aromatic compound instead of an alkene was the coupling partner the aromaticity with this carbopallada-tion of a C=C double bond would have to be sacrificed in step 4. Typically, Heck reactions can only be run at a temperature of 100 °C even if they proceed without any such energetic effort. This is why this additional energetically demanding loss of aromaticity is not feasible. 

In reactions of alkenyl triflates with stereogenic C=C double bonds, coupling reactions of these kinds convert the Csp2—X bond of the alkenyl triflate into the Csp2—C bond of the substitution product with complete retention of configuration. The stereoselective synthesis of a 1,3-diene from an alkenyl triflate and (vinyl)2CuLi provides an example (Figure 13.1). 

One of the things the Heck reaction cannot do, at least not in an intermolecular fashion, is couple alkenyl triflates (bromides, iodides) with metal-free aromatic compounds,... 

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