Propargyl alcohols coupling

Phenyl-substituted propargyl alcohol couples with 3-iodopyridine to furnish (49) (Scheme 10). On reaction of the 2-iodopyridine (50), however, it was found that the initial alkynylation product (51) rearranged to form the corresponding chalcone (52). The same rearrangement occurs in pyrimidines when the iodine is located in an electrophilic position. In reactions with the corresponding methylpropargyl alcohol, the reaction stops after... 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

Scheme 5.1-27 The zinc triflate-catalyzed coupling of alkynes with aldehydes to give propargyl alcohols in an ionic liquid.

Eventually, indole acetic acid 2 was prepared from iodoaniline 28 and propargyl alcohol derivative 61 via the newly developed coupling reaction followed by a cyanide displacement-hydrolysis sequence, as shown in Scheme 4.16. 

The C,0-bis-TES side chain 61 was prepared quantitatively from propargyl alcohol and TESC1 using n-BuLi as a base. Pd-catalyzed coupling of iodoaniline 28 with bis-TES side chain 61 in the presence of 1.5equiv of MgS04 and 5equiv of... 

The final example demonstrates that microwave irradiation allows a perfect fine-tuning of reaction conditions to obtain different products from the same starting materials. In the procedure developed by Garcfa-Tellado and coworkers [41], two domino processes were coupled. The first process consists of a high-yielding synthesis of enol-protected propargylic alcohols 10-111 starting from alkyne 10-109 and aldehyde 10-110 (Scheme 10.28). In the second process, transformation into... 

Tejedor and coworkers have utilized a combination of two domino processes for a microwave-promoted synthesis of tetrasubstituted pyrroles [344]. The protocol combines two coupled domino processes the triethylamine-catalyzed synthesis of enol-protected propargylic alcohols and their sequential transformation into pyrroles through a spontaneous rearrangement from 1,3-oxazolidines (Scheme 6.183). Overall, these two linked and coupled domino processes build up two carbon-carbon bonds, two carbon-nitrogen bonds, and an aromatic ring in a regioselective and efficient manner. The tetrasubstituted pyrroles could be directly synthesized from the enol-protected propargylic alcohols and the primary amines by microwave irradia-... 

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>. 

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 . 

Denmark pursued intramolecular alkyne hydrosilylation in the context of generating stereodefined vinylsilanes for cross-coupling chemistry (Scheme 21). Cyclic siloxanes from platinum-catalyzed hydrosilylation were used in a coupling reaction, affording good yields with a variety of aryl iodides.84 The three steps are mutually compatible and can be carried out as a one-pot hydro-arylation of propargylic alcohols. The isomeric trans-exo-dig addition was also achieved. Despite the fact that many catalysts for terminal alkyne hydrosilylation react poorly with internal alkynes, the group found that ruthenium(n) chloride arene complexes—which provide complete selectivity for trans-... 

Dimethyl propargyl alcohol 95 serves as a mask for the corresponding terminal acetylene. Therefore, basic cleavage of 95 unveiled the terminal acetylene, which was coupled in situ with 2-bromobenzothiazole in the presence of a phase-transfer catalyst to afford the unsymmetrical diarylbutadiyne 96 [53],... 

This CrCl2/NiCl2-mediated coupling can also be used to obtain a propargylic alcohol with high diastereoselectivity (equation I). The aldehyde in this case under-... 

Coupling of excess (Z)-l,2-dichloroethene (217) with propargyl alcohol first led to the enyne 218, which, when subjected to a second Pd-catalyzed coupling step with trimethylsilylacetylene, provided the mixed diacetylene 219. With all carbon atoms assembled, the allene function was generated by first producing the (unprotected) hydrazine derivative 220, which on treatment with either diethyl azodicarboxylate (DEAD) or 4-methyl-l,2,4-triazoline-3,5-dione (MTAD) under anaerobic conditions at 0 °C yielded the hydrocarbon 27. According to mechanistic studies, the latter process leads first to a mixture of ( )- and (Z)-diazenes. Sigmatropic elimination of... 

The propargylic alcohol 102, prepared by condensation between 100 and the lithium acetylide 101, was efficiently reduced to the hydrocarbon 103, which on treatment with potassium tert-butoxide was isomerized to the benzannulated enyne-allene 104 (Scheme 20.22) [62], At room temperature, the formation of 104 was detected. In refluxing toluene, the Schmittel cyclization occurs readily to generate the biradical 105, which then undergoes intramolecular radical-radical coupling to give 106 and, after a prototropic rearrangement, the llJ-f-benzo[fo]fluorene 107. Several other HJ-f-benzo[fo]fluorenes were likewise synthesized from cyclic aromatic ketones. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

From unsymmetrical propargyl alcohol and propargyl amine derivatives as coupling partners of diynes, the corresponding axially chiral alcohols and amines were obtained in almost perfect diastereo- and enantioselectivities (Scheme 11.13). 

Scheme 18 Coupling of an allenylidene ligand with allyl and propargyl alcohol...

Scheme 7.32 Reductive coupling reactions of propargylic alcohols.

This side-reaction is most serious in the case of acetylenes RC=CH with a relatively low acidity aliphatic 1-alkynes, e.g. 1-octyne, and acetylenic alcohols HCaC(CH2)nOH with n > 2, give reduced yields (40-50%) in the coupling reaction. In many other reactions, yields are high. Since the bromoalkyne usually has the highest "added value", economical considerations prescribe the use of an excess of the free acetylene, especially when it is inexpensive, e.g. propargyl alcohol. The mechanism of the Cadiot-Chodkiewicz reaction has not been studied in detail, but is seems likely that a copper acetylide ROCCu is formed first it often appears as a yellowish suspension. 

Coupling or2-Iodothiophene with O-Protected Propargyl Alcohol in the Presence of Catalytic Amounts oT PdfPPhj) and Cul... 

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