Alcohols palladium catalyzed

Coupling of vinyl halides with allyl alcohols/ Palladium-catalyzed coupling of vinyl halides with allylic alcohols under usual Heck conditions results in a complex mixture of products. Addition of silver carbonate and a phase-transfer catalyst can result in a palladium-catalyzed coupling of vinyl halides with a primary allylic alcohol to give a y, -enal, with retention of configuration of the vinyl halide. 

The benzyl group has been widely used for the protection of hydroxyl functions in carbohydrate and nucleotide chemistry (C.M. McCloskey, 1957 C.B. Reese, 1965 B.E. Griffin, 1966). A common benzylation procedure involves heating with neat benzyl chloride and strong bases. A milder procedure is the reaction in DMF solution at room temperatiue with the aid of silver oxide (E. Reinefeld, 1971). Benzyl ethers are not affected by hydroxides and are stable towards oxidants (e.g. periodate, lead tetraacetate), LiAIH, amd weak acids. They are, however, readily cleaved in neutral solution at room temperature by palladium-catalyzed bydrogenolysis (S. Tejima, 1963) or by sodium in liquid ammonia or alcohols (E.J. Rcist, 1964). 

Oxidative Carbonylation of Ethylene—Elimination of Alcohol from p-Alkoxypropionates. Spectacular progress in the 1970s led to the rapid development of organotransition-metal chemistry, particularly to catalyze olefin reactions (93,94). A number of patents have been issued (28,95—97) for the oxidative carbonylation of ethylene to provide acryUc acid and esters. The procedure is based on the palladium catalyzed carbonylation of ethylene in the Hquid phase at temperatures of 50—200°C. Esters are formed when alcohols are included. Anhydrous conditions are desirable to minimize the formation of by-products including acetaldehyde and carbon dioxide (see Acetaldehyde). 

A low temperature catalytic process has been reported (64). The process involves the divalent nickel- or zero-valent palladium-catalyzed self-condensation of halothiophenols in an alcohol solvent. The preferred halothiophenol is -bromothiophenol. The relatively poor solubiHty of PPS under the mild reaction conditions results in the synthesis of only low molecular weight PPS. An advantage afforded by the mild reaction conditions is that of making telecheHc PPS with functional groups that may not survive typical PPS polymerization conditions. 

An unusual by-product was obtained in small yield in palladium-catalyzed reduction of 2-amino-4,5-dimethoxyindanone hydrochloride, The reduction was done in two stages first, a rapid absorption of 1 mol of hydrogen at 38 C to give the amino alcohol, and then a much slower reduction in the presence of HCIO4 at 70 "C. The rearranged by-product was shown to arise from attack of acid on the amino alcohol (50), Resistance to hydrogenolysis is characteristic of / -amino aromatic alcohols (56), a fact that makes reduction of aromatic oximino ketones to amino benzyl alcohols a useful synthetic reaction. 

Recently, Y. Yamamoto reported a palladium-catalyzed hydroalkoxylation of methylene cyclopropanes (Scheme 6-25) [105]. Curiously, the catalysis proceeds under very specific conditions, i.e. only a 1 2 mixture of [Pd(PPh3)4] and P(o-tolyl)3 leads to an active system. Other combinations using Pd(0 or II) precursors with P(o-tolyl)3 or l,3-bis(diphenylphosphino)propane, the use of [Pd(PPh3)4] without P(o-tolyl)3 or with other phosphine ligands were all inefficient for the hydroalkoxylation. The authors assumed a mechanism in which oxidative addition of the alcohol to a Pd(0) center yields a hydrido(alkoxo) complex which is subsequently involved in hydropal-ladation of methylenecyclopropane. 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

A solid-phase version of the palladium-catalyzed carbonyl allylation of aldehydes by allylic alcohol has been described. Thus, allylation of resin-bound aldehyde (P = Merrifield resin) with allylic alcohols (e.g., MeCH=CHCH2OH) in the presence of SnCl2 afforded the homoal-lylic alcohols under different solvent conditions, in DMSO and aqueous DMSO respectively (Eq. 8.45).102... 

Diazonium salts react with various nucleophiles in water (Eq. 11.62).106 In acidic aqueous solution, p-pheny I e ncbis di azo ni um ion reacts with alcohols more rapidly than it does with water.107 In the presence of nucelophiles such as halides, the substitution products are obtained. Furthermore, diazonium salts of aromatic compounds are excellent substrates for palladium-catalyzed coupling reactions such as the Heck-type reactions in water. 

Balme and coworkers reported on a procedure for the preparation of highly functionalized furans of type 2-940 (Scheme 2.210) [480]. Their approach is based on a nucleophilic Michael addition of propargyl alcohols 2-937 to alkylidene or aryl-idenemalonates 2-938, followed by a palladium-catalyzed cydization via the carban-ion 2-939. The reactions with propargyl alcohol led to the formation of only one di-... 

The first palladium-catalyzed formation of aryl alkyl ethers in an intermolecular fashion occurred between activated aryl halides and alkoxides (Equation (28)), and the first formation of vinyl ethers occurred between activated vinyl halides and tin alkoxides (Equation (29)). Reactions of activated chloro- and bromoarenes with NaO-Z-Bu to form /-butyl aryl ethers occurred in the presence of palladium and DPPF as catalyst,107 while reactions of activated aryl halides with alcohols that could undergo /3-hydrogen elimination occurred in the presence of palladium and BINAP as catalyst.110 Reactions of NaO-/-Bu with unactivated aryl halides gave only modest yields of ether when catalyzed by aromatic bisphosphines.110 Similar chemistry occurred in the presence of nickel catalysts. In fact, nickel catalysts produced higher yields of silyl aryl ethers than palladium catalysts.108 The formation of diaryl ethers from activated aryl halides in the presence of palladium catalysts bearing DPPF or a CF3-subsituted DPPF was also reported 109... 

The palladium-catalyzed cross-coupling reaction featured in this procedure occurs under neutral conditions in the presence of many synthetically useful functional groups (e.g. alcohol, ester, nitro, acetal, ketone, and aldehyde). The reaction works best in N,N-dimethylformamide with bis(triphenylphosphine)palladium(ll) chloride, PdCI2(PPh3)2, as the catalyst. Lithium chloride is added to prevent decomposition of the catalyst.143 13 It is presumed that conversion of the intermediate aryl palladium triflate to an aryl palladium chloride is required for the transmetallation step to proceed.9... 

A gallium metal-mediated allylation of pyrrole led selectively to the formation of the 3-substituted pyrroles <06TL3535>. In contrast, a palladium-catalyzed allylation of pyrrole with allylic alcohols performed in the presence of triethylborane led to 2-substituted pyrroles <06H(67)535>. 

As part of the same study, the capacity of this novel resin to act as an allyl cation scavenger was demonstrated in a palladium-catalyzed O-alloc deprotection of O-alloc benzyl alcohol (Scheme 7.107) [125], Benzyl alcohol was obtained in high yield with only trace amounts of by-product, thereby eliminating the need for further purification. The resulting C-allylation of the resin was evident from the presence of C-allyl signals in the relevant MAS-probe 1H NMR spectrum. 

Scheme 7.107 Palladium-catalyzed deprotection of O-alloc benzyl alcohol employing the scavenging resin CHD-SR.

Another route to the diol monomer is provided by hydroformylation of allyl alcohol or allyl acetate. Allyl acetate can be produced easily by the palladium-catalyzed oxidation of propylene in the presence of acetic acid in a process similar to commercial vinyl acetate production. Both cobalt-and rhodium-catalyzed hydroformylations have received much attention in recent patent literature (83-86). Hydroformylation with cobalt carbonyl at 140°C and 180-200 atm H2/CO (83) gave a mixture of three aldehydes in 85-99% total yield. 

The stereochemistry of the dialkoxylation arises from two external attacks by the alcohol, one on the rr-diene complex and the second on the intermediate jr-allyl complex. This is in accordance with the other palladium-catalyzed 1,4-syn additions discussed above. 

If the side chain with the nucleophile is situated in the 1-position of the conjugated diene, a palladium-catalyzed spirocyclization occurs. In this case stereoselective oxa-spirocyclizations were obtained from the diene alcohols 59 and 60 (equation 23 -25)58. The reaction worked well for the formation of a tetrahydrofuran and tetrahydropyran in the spirocyclization. In the absence of chloride ions 59 gave high yields of the acetoxy oxaspirocyclic compound 61 via a 1,4-anti addition across the diene (equation 23). In the presence of stoichiometric amounts of LiCl a 1,4-syn oxychlorination took place and allylic chloride 62 was obtained (equation 24). Under chloride-free conditions, cyclohep-tadiene alcohol 60 afforded oxaspirocyclic acetate 63 (equation 25). 

The oxaspirocyclization was applied to the synthesis of theaspirone and vitispirane (equations 26 and 27)59. Under slightly modified reaction conditions where water is employed as the major solvent, palladium-catalyzed 1,4-oxidation of 64 afforded 65. Alcohol 65 was oxidized to theaspirone, which was obtained as a 1 1 isomeric mixture of cis and trans isomers. When the analogous reaction was performed at a lower pH by the use of trifluoroacetic acid, vitispirane was formed in high yield, again as a 1 1 isomeric mixture of stereoisomers. 

Trifluoroethylfurans can be obtained from (Z)-2-alkynyl-3-trifluoromethyl allylic alcohols 75 through palladium-catalyzed cyclization-isomerization procedures <00JOC2003>. 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

Several examples of transition metal catalysis for the synthesis of piperidines appeared this year. Palladium catalyzed intramolecular urethane cyclization onto an unactivated allylic alcohol was described as the key step in the stereoselective synthesis of the azasugar 1-deoxymannojirimycin . A new synthetic entry into the 2-azabicyclo[3.3.1]nonane framework was accomplished through a palladium mediated intramolecular coupling of amine tethered vinyl halides and ketone enolates in moderate yields . A palladium catalyzed decarboxylative carbonylation of 5-vinyl... 

Muller and co-workers reported the three-component one-pot synthesis of various pyrimidines through the in situ generation of unsaturated carbonyl compounds. The palladium catalyzed coupling of aryl halides bearing electron withdrawing substituents 7 with propargyl alcohols 8 produced unsaturated carbonyl compounds 9 after isomerization, which condensed with amidines 10 to form triaryl pyrimidines 11 . 

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