Kinetic propargylic alcohols

Jacobs and Fenton (202) were the first to suggest the possible intermediacy of ion 242 in the hydrolysis of trisubstituted allenyl halides to give the corresponding propargyl alcohols as products. A detailed and elegant study of the solvolysis of a series of triarylchloroallenes, 243, has recently been carried out by Schiavelli and co-workers (203). Excellent first-order kinetics... 

Tao B, Ruble JC, Hole DA, Fu GC (1999) Nonenzymatic kinetic resolution of propargylic alcohols by a planar-chiral DMAP Derivative crystallographic characterization of the acylated catalyst. J Am Chem Soc 121 5091-5092... 

The methanolic cupric bromide oxidation of propargyl alcohol to trans-BrCH-CBrCH20H (30%) and Br2C=CBrCH20H (18%) and, under other reaction conditions, Br2C-CBr-CH20H (93 %) follows simple second-order kinetics with a rate coefficient of 1.5 x 10 l.mole . sec at 64 °C. A mechanism of ligand-transfer in a 7t-complex is proposed. ... 

Cr(II) readily reduces a wide range of (but not all) acetylenic compounds to give mainly the corresponding rra/ij-olefin. Propargyl alcohol is reduced with kinetics ... 

Benzotetramisole 213 has been identified as an effective catalyst for kinetic resolution of sec-benzylic and propargylic alcohols 214 to give 215 in excellent enantioselectivity O60L1351 06OL4859>. The benzotetramisole-catalyzed kinetic resolution has been extended to 2-oxazolidinone 217 via enantioselective /V-acylation <06JA6536>. 

From the electronic populations on the vinylic hydrogens, the acidity of vinylic C—H was estimated to be higher in cyclopropenone than in cyclopropene (0.684 e/ 0.776 e). This agrees with kinetic measurements of the H-D-exchange at n-propyl cyclopropenone23 which showed an acidity of the vinylic C—H even higher than that of the acetylenic C—H in the reference compound propargyl alcohol. 

Equation (81)), while the other two C=C double bonds in the structure are intact. Under the same reaction conditions, the racemic carvone is also resolved kinetically with a KR/KS ratio of 33 1. Asymmetric hydrogenation of a,/Tacetylenic ketones to chiral propargylic alcohols is still unavailable. 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

The coupling of propargyl alcohol with copperfii) acetate in pyridine constitutes a notable exception to the kinetic behaviour described above , but it has been shown that the behaviour is peculiar to this particular system Thus normal kinetic behaviour is found for Cu(OAc)o-pyridine coupling of acetals and ethers of propargyl alcohol, and for propargyl alcohol itself when Cu(n) in aqueous ammonia is used . 

Here is a simple example in the field of prostaglandin synthesis where 9-BBN was used on a protected optically active propargyl alcohol.12 The starting material is identical to the alkyne 78 that we reacted with Bu3SnH above and the result is the same - cis hydrometallation with the metal atom at the terminus. However that was a thermodynamically controlled stereoselective radical chain reaction while this is a kinetically controlled stereospecific electrophilic addition to give the vinyl borane -87. 

Resolution by transesterification. Using vinylic acetates to esterify allyl alcohols, propargyl alcohols, 2-phenylthiocycloalkanols, a-hydroxy esters," methyl 5-hydroxy-2-hexenoates, and 2-substituted 1,3-propanediols, the enantioselective esterification provides a means of separation of optical isomers. Vinyl carbonates are also resolved by lipase-mediated enantioselective conversion to benzyl carbonates. Other esters that have also been used in the kinetic resolution include 2,2,2-tri-fluoroethyl propionate. There is a report on a double enantioselective transesterification" of racemic trifluoroethyl esters and cyclic meso-diols by lipase catalysis. 

Garratt and coworkers " studied the addition of benzeneselenenyl chloride to a large number of propargyl alcohols. The reaction was performed in dichloromethane with the alcohol in excess. Essentially quantitative yields of anti addition products were obtained, some of them pure Markovnikov, others pure anti-Markovnikov and a few a mixture of both. The anti-Markovnikov products are formed by kinetic control. They slowly isomer-ized to the Markovnikov products. 

The ophcally active Pd complex with a chiral allenyl ligand undergoes epimer-izahon in the presence of a catalytic amount of Pd(0) complex. This reaction does not involve the isomerization to the propargyl complex, but takes place via a dinuclear intermediate as depicted in Scheme 5.39. The -allenyl ligand in the dinuclear palladium intermediate may racemize via a vinyl-vinyidene intermediate. This type of reaction is prohahly involved in a kinetic resolution of racemic propargyl alcohols promoted hy chiral transihon metal complex [203]. The intermolecular allyl ligand transfer from Pd to Ee complexes occurs under... 

These observations have been found to be of general nature in different hydrochloric acid as well as varying propargyl alcohol concentrations. While most of the observed effects in Fig.19 could be explained in terms of conventional electrochemical kinetics, the factis that in the presence of oxygen and propargyl alcohol the cathodic curve shows a limiting current behavior and is rather difficult to understand. However, if one were to assume an iron - inhibitor chelate film... 

Tanaka et al. developed a Rh-catalyzed asymmetric one-pot transesterification and [2+2+2] cyclotrimerization using nonracemic ligand 415 in the synthesis of enantio-enriched 3,3-disubstituted phthalides (R R ) (Scheme 2-39)P The chiral Rh complex with 415 efficiently desymmetrized dipropargyl alcohols 413 (R = R -OC-) in the reaction with 412 to give phthalides 414 (R = R -C=C-) in up to 87% yield and 93% ee. Also, the kinetic resolution of racemic tertiary propargylic alcohols... 

The greatest advantage of this approach is the circumvention of the use of optically active tertiary propargylic alcohols. The chiral Rh complex could efficiently desymmetrize the achiral alcohol to give the 3,3-disubstituted phthalides products in up to 87% isolated yield and 93% ee. The kinetic resolution of racemic tertiary propargylic alcohols provided disubstituted phthalides with up to 89% 3deld and up to 93% ee. 

Scheme 41.4 Kinetic resolution of propargylic alcohols by Birman et al...

Recently, Lin et al. demonstrated that the propargyl alcohol could participate in such a transformation for the synthesis of chiral dihydrofurans [53]. The reaction began with a challenging oxa-Michael addition to cinnamaldehyde derivatives, which was followed by a secondary amine/Pd complex-catalyzed nucleophilic addition/ isomerization of the alkyne moiety in excellent yields and enantioseleclivities (Scheme 9.58). Since the oxa-Michael addition of propargyl alcohol to 0[,P-unsaturated aldehydes was a slow process, this cascade reaction proceeded through a dynamic kinetic asymmetric transformation (DYKAT) process, whereby it made the overall reaction proceed efficiently and with high stereocontrol using the second reaction with precise stereocontrol to shift the first reversible oxa-Michael addition selectively. 

The kinetics of hydrogenation of propargyl alcohol on palladium black... 

Fig. 11. Effect of cadmium sulfate on hydrogenation kinetics of propargyl alcohol on palladium black at 20 C. 1) Water 2) 10 N cadmium sulfate 3) 10" N cadmium sulfate 4) 5-10 cadmium sulfate 5) 3 N cadmium sulfate.

In solutions of cadmium sulfate (10 to 0.1 N) the amount of hydrogen consumed in the hydrogenation of propargyl alcohol increases and approaches the theoretical value. This is due to lower isomeriz-ing ability of the catalyst modified with cadmium. In 0.1-1 N solutions of cadmium sulfate the kinetics of the process change as well. The... 

Upadhyaya, H.R, A. Kumar, RD. Naik, A.V. Sapre, and J.R Mittal (2001), Kinetics of OH radical reaction with allyl alcohol (H2CCHCH2OH) and propargyl alcohol (HCCCH2OH) studied by LIP, Chem. Phys. Lett., 349, 279-285. 

Various racemic secondary alcohols with different substituents, eg, a-hydroxyester (60), are resolved by PFL neady quantitatively (75). The effect of adjacent unsaturation on enzyme-catalyzed kinetic resolutions was thoroughly studied for a series of allylic (61), propargylic (62), and phenyl-substituted 2-alkanols (76,77). Excellent selectivity was observed for (E)-allylic alcohols whereas (Z)-isomers showed poor selectivity (76). 

The hydrolysis/alcoholysis of (309 R = Pr", Bu, allyl, propargyl) with various alcohols and water caused only a slight difference in the heat of activation for R but, for a fixed R die variation was much greater. The kinetics could be described by a Taft-Pavelich equation.283... 

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