Palladium catalysts lactonization

Trost has reported an elegant case of stereochemical relay in a conforma-tionally flexible system. In the presence of palladium catalysts, lactone 11 was shown to react with malonate in high yield (Equation 1) [45]. It is noteworthy that the putative. r-allylpalladium intermediate 12 is configurationally stable and affords product 13 with high diastereo- and regioselectivity (>95 5 dr, 90% yield). 

Intramolecular cycloadditions of substrates with a cleavable tether have also been realized. Thus esters (37a-37d) provided the structurally interesting tricyclic lactones (38-43). It is interesting to note that the cyclododecenyl system (w = 7) proceeded at room temperature whereas all others required refluxing dioxane. In each case, the stereoselectivity with respect to the tether was excellent. As expected, the cyclohexenyl (n=l) and cycloheptenyl (n = 2) gave the syn adducts (38) and (39) almost exclusively. On the other hand, the cyclooctenyl (n = 3) and cyclododecenyl (n = 7) systems favored the anti adducts (41) and (42) instead. The formation of the endocyclic isomer (39, n=l) in the cyclohexenyl case can be explained by the isomerization of the initial adduct (44), which can not cyclize due to ring-strain, to the other 7t-allyl-Pd intermediate (45) which then ring-closes to (39) (Scheme 2.13) [20]. While the yields may not be spectacular, it is still remarkable that these reactions proceeded as well as they did since the substrates do contain another allylic ester moiety which is known to undergo ionization in the presence of the same palladium catalyst. 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

Cyclic alkynyl carbonates undergo carbonylation in the presence of a palladium catalyst and carbon monoxide (5 MPa) in MeOH to give allenic carboxylates (Eq. 9.118) [92], Bu3P proved superior to Ph3P as the catalyst ligand. An enynyl cyclic carbonate underwent double vicinal carbonylation at 80 °C to produce a five-membered lactone product in 52% yield (Eq. 9.119). When the reaction was performed at 50 °C, the bicyclic enone lactone was produced in 75% yield along with 10% of the y-lactone. 

A highly efficient method for the synthesis of medium-sized rings (examples of 17-, 15-, 10- and 5-membered carbocycles, lactones and lactams) without high-dilu-tion conditions was developed by Trost et al. for example, precursor 204 with a palladium catalyst led to an E-Z mixture of 205 in 86% yield, and subsequent hydrogenation then provided the 10-membered lactam ring 206 in 85% yield (Scheme 15.66) [132],... 

Hydrogenation of endiandric acid (555) with an aged palladium catalyst afforded the dihydro derivative 556 which isomerized to the triquinane lactone 557 when heated with HBr in acetic acid... 

Lactone synthesis.2 Carbonylation of simple organic halides can be carried out readily with several palladium catalysts such as bis(diphenylphosphinoethane)-his(triphenylphosphine)palladium(0) and dichlorobis(triphenylphosphinc)pal-ludium(ll). The latter catalyst is preferred because it is stable and easily converted to Pd(0) in situ. Carbonylation of halo alcohols provides a useful synthesis of various lactones. 

Arene(tricarbonyl)chromium complexes, 19 Nickel boride, 197 to trans-alkenes Chromium(II) sulfate, 84 of anhydrides to lactones Tetrachlorotris[bis(l,4-diphenyl-phosphine)butane]diruthenium, 288 of aromatic rings Palladium catalysts, 230 Raney nickel, 265 Sodium borohydride-1,3-Dicyano-benzene, 279 of aryl halides to arenes Palladium on carbon, 230 of benzyl ethers to alcohols Palladium catalysts, 230 of carboxylic acids to aldehydes Vilsmeier reagent, 341 of epoxides to alcohols Samarium(II) iodide, 270 Sodium hydride-Sodium /-amyloxide-Nickel(II) chloride, 281 Sodium hydride-Sodium /-amyloxide-Zinc chloride, 281 of esters to alcohols Sodium borohydride, 278 of imines and related compounds Arene(tricarbonyl)chromium complexes, 19... 

Tritiated GAs of very high specific radioactivity have been prepared by catalytic reduction. The 1,2 double bond of GAq can be selectively reduced, using a partially poisoned palladium catalyst, to give [1,2-3h2]GA] (7 -,(75,76), although some reduction of the 16,17 double bond and the lactone also occurs (76). Introduction of 3h at sites other than carbon atoms 1 and 2 has also been found (76). [3h]GAI has been prepared from GAy by a similar method JT7). [3h]GA was converted... 

The unsaturated 3a-acetoxy-17-formyl-16-etiocholen-lip-ol-18-one lip,18-lactol is hydrogenated in the presence of palladium catalyst to saturate the 16,17-double bond, and then saturated aldehyde are oxidized by treatment with chromic oxide in pyridine to give 3a-acetoxy-lip-ol-18-one-pregnane lip,18-lactone 17-carboxylic acid. 

This is ordinary electrophilic addition, with rate-determining protonation as the first step. Certain other alkynes have also been hydrated to ketones with strong acids in the absence of mercuric salts. Simple alkynes can also be converted to ketones by heating with formic acid, without a catalyst.Lactones have been prepared from trimethylsilyl alkenes containing an hydroxyl unit elsewhere in the molecule, when reacted with molecular oxygen, CuCla, and a palladium catalyst. ... 

Allene carboxylic acids have been cyclized to butenolides with copper(II) chloride. Allene esters were converted to butenolides by treatment with acetic acid and LiBr. Cyclic carbonates can be prepared from allene alcohols using carbon dioxide and a palladium catalyst, and the reaction was accompanied by ary-lation when iodobenzene was added. Diene carboxylic acids have been cyclized using acetic acid and a palladium catalyst to form lactones that have an allylic acetate elsewhere in the molecule. With ketenes, carboxylic acids give anhydrides and acetic anhydride is prepared industrially in this manner [CH2=C=0 + MeC02H (MeC=0)20]. 

A bis(dicyclohexylphosphino)butane (DCPB)-based palladium catalyst was found to catdyze the analogous reaction between isoprene and CO2 [11]. A mixture of lactones 7 and 8 is obtained but the yield of co-oligomerization products is significantly lower (8%) than for the reaction of 1,3-butadiene. 

In Figure 6 this principle is demonstrated for the telomerization of butadiene with carbon dioxide yielding a d-lactone (Eq. 4). The reaction is carried out in a homogeneous acetonitrile solution using a palladium catalyst. After distillation of the acetonitrile in the second unit, the product/catalyst mixture is treated with the extractant, 1,2,4-butanetriol, which dissolves the product but not the catalyst [55]. The catalyst is then recycled to the reactor in a small amount of the liquid product. The main quantity of the lactone is separated from the extractant by a second distillation step. 

Carbonylation of o-allylbenzyl halides.1 Carbonylation (600 psi) of o-allylbenzyl chloride (1) in the presence of triethylamine (2 equiv.) and in the presence of this palladium catalyst (5 mol %) provides the benzoannclatcd cnol lactone (2) in 78% yield. 

---