Enol triflate carbonylation

Carbonylation of enol triflates. Carbonylation of enol triflates catalyzed by this Pd(II) complex in the presence of an alcohol or an amine results in one-carbon homologated a,0-unsaturated esters or amides in 70-95% yield.4 Example ... 

The most useful pseudo-halides are aryl triflates (trifluoromethylsulfonates) of phenols and enol triflates derived from carbonyl compounds[4,5,6]. 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

Carbonylation of enol triflates derived from ketones and aldehydes affords Q,/)-unsaturated esters[332]. Steroidal esters are produced via their aryl and enol triflates[328]. The enol triflate in 477 is more reactive than the aryl tritlate and the carbonylation proceeds stepwise. First, carbonylation of the enol triflate affords the amide 478 and then the ester 479 is obtained in DMSO using dppp[333]. 

Carboxylic acids are produced in water. Selection of solvents is crucial and the carbonylation of the enol triflate 480 can be carried out in aqueous DMF, and that of the aryl triflate 481 in aqueous DMSO using dppf as a ligand[328,334]. The carbonylation of the enol triflate 482 to form the a, 0. unsaturated acid 483 using dppf as a ligand in aqueous DMF has been applied in the total synthesis of multifunctionalized glycinueclepin[335]. 

Concealed within spirocyclic intermediate 16 are rings B and F of ginkgolide B. Intermediate 16 is readily formed in two steps from a readily available starting material and it contains a strategically placed ketone carbonyl group which provides several options for further advance. A particularly straightforward route to 15 includes the conversion of ketone 16 into enol triflate 21 by means of McMurry s protocol.16 Thus, enolization of 16 with LDA in dimethoxyethane at -78 °C followed by triflation of the enolate oxygen atom with /V-phenyltrifluoromethanesulfonimide furnishes enol triflate 21 in a yield of 80%. 

Alkenyl trifluoromethanesulphonates (enol triflates) undergo Heck coupling with alkenes efficiently (equation 123)209a 215. This reaction is a useful variation of the use of vinyl halides not only because they are easy to prepare from the corresponding carbonyl compounds, but also because yields are good, and the stereochemistry of the triflate is largely maintained. 

Hydroboration and oxidation of 160 yields an alcohol that is subsequently oxidized with PDC to give ketone compound 161. Enolization and triflation converts this compound to enol triflate 162, which can be further converted to x,/i-unsaturated ester 163 upon palladium-mediated carbonylation methox-ylation. The desired alcohol 164 can then be readily prepared from 163 via DIBAL reduction. Scheme 7 50 shows these conversions. 

The substrates with the alkenyl iodide (138-141) moiety could be totally converted into the desired products (138a, 139a, 138b-140b, 138c-141c) in4-8 h, while the enol triflate (142) reacted slowly. The bromo derivative (144) is unreactive and no carbonylation product was observed even after prolonged reaction times. 

The carbonylation of the same substrates (138-144) with several A-substituted hydrox-ylamines proceeds with the same order of substrate reactivity (Scheme 67). In particular, with steroidal alkenyl iodides 138-141 and enol triflates 142 and 143 complete conversion of the substrates could be achieved, in the latter cases (142 and 143) with long reaction times. The analogue bromo derivative 144 is completely unreactive. 

The carbonylation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356], Carbonylation of iodobenzene in the presence of odiaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357], The carbonylation of aryl iodides in the presence of pentafluor-oaniline affords 2-arylbenzoxazoles directly. 2-Arylbenzoxazole is prepared indirectly by the carbonylation of n-aminophenol[358]. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonylation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

Dialkylboron trifluoromethanesulfonates (triflates) are particularly useful reagents for the preparation of boron enolates from carbonyl compounds, including ketones, thioesters and acyloxazolidinones.4 Recently, the combination of dicylohexylboron trifluoromethanesulfonate and triethylamine was found to effect the enolization of carboxylic esters.5 The boron-mediated asymmetric aldol reaction of carboxylic esters is particularly useful for the construction of anti (3-hydroxy-a-methyl carbonyl units.6 The present procedure is a slight modification of that reported by Brown, et al.2... 

The conversion of carbonyl compounds to their enol triflates provides a very simple way to couple the carbonyl carbon to an alkene. In general, however, aryl... 

In addition to halides, some pseudohalides undergo facile oxidative addition to Pd and Ni complexes. Trifluoromethanesulfonates (triflates), namely aiyl triflates 3 derived from phenols and enol triflates of carbonyl compounds, are most useful. 

Alkenyl halides and their pseudohalides also react with Pd(0) to form the alkenylpalladium intermediates 11, and their transformations are summarized in Scheme 3.4. In addition to alkenyl halides, the enol triflates 12 undergo oxidative addition, showing that carbonyl compounds are useful starting compounds for Pd-catalysed reactions. 

Triflates derived from phenols are carbonylated to form aromatic esters by using Pd-Ph3P. The carbonylation of triflates is 500 times faster if DPPP (XLIV) is used [219]. This reaction is a good preparative method of benzoates from phenols and naphthoates from naphthols [220]. Carbonylation of enol triflates derived from ketones and aldehydes affords a,/Cunsaturated esters. The enol triflate in 451 is more reactive than the aryl triflate and the carbonylation proceeds stepwise chemoselectively. At... 

Similar hydrogenolysis (Pt02 or Raney Ni) of enol triflates provides a general method for conversion of a carbonyl group to a methylene group (60-90% yield). 

The Nazarov cyclization has been featured in a variety of synthetic endeavors involving both natural and unnatural products. In the area of polyquinane natural products ( )-hirsutene (88), ( )-mod-hephene (89), ( )-silphinene (90), ( )-A 2)-capnellene (91) and ( )-cedrene, have all been prepared (Scheme 37). The synthesis of (91) is noteworthy in the iterative use of the silicon-directed Nazarov cyclization. TIk divinyl ketones were constructed by the carbonylation-coupling of enol triflates (92) and (95) with the -silylvinylstannane (Scheme 38). llie diquinane (94), obtained from Nazarov cyclization of (93), was transformed into enol triflate (95) which was coupled with the -silylvinylstaimane as before. Silicon-directed Nazarov cyclization of (96) was highly diastereoselective to provide the cis,anti,cis isomer of (16). The synthesis was completed by routine manipulations. 

Another approach developed by the Vogel group relies on a carbonylative Stille cross-coupling between stannylated glucal derivative 410 and enol triflate 412 derived from isolevoglucosenone [152] (O Scheme 80). 

Ceccarelli, S., Piarulli, U., Gennari, C. Effect of ligands and additives on the palladium-promoted carbonylative coupling of vinyl stannanes and electron-poor enol triflates. J. Org. Chem. 2000, 65, 6254-6256. 

Enol triflates have emerged as attraetive alternatives to vinyl halides in the Stille coupling partner due to their ease of preparation from readily available carbonyl compounds. The addition of LiCI has been found to be beneficial to Stille enol triflate coupling reactions. Thus, it was not surprising that coupling 5-tributylstannylpyrimidine to enol triflate 134 proceeded in good yield in the presence of LiCI. In this case, the addition of Cul as cocatalysts was found to also be beneficial to the reaction outcome [57]. 

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