Hydroxylation propargylic

Cyclizations. Cyclization of hydroxylated propargyl sulfones may involve isomerization to the corresponding allenyl sulfones which should behave as Michael acceptors. Access to the indolizidine skeleton by an intramolecular Michael reaction of 5-tosyl-4-pentenamide and subsequent alkylation at nitrogen and carbon is quite efficient. A synthesis of resorcinols from dimethyl acetonedicarboxylate and alkyl alkynoates involves a Michael reaction-Dieckmann cyclization sequence. 

PED. The triple-bond positional isomers of PED, lO-(l-propynyl) estr-4-ene-3,17-dione, and the 10-ethynyl, 10-cyano and 1-methyl cyanide analogs were not suicide inhibi-torsi2l,l3l,l32 10-[[li ]-l-hydroxy-2-propynyl], 10-[[lS]-l-hydroxy-2-propynyl] and 10-(l-oxo-2-propynyl) estr-4-ene-3,17-dione were prepared as potential PED metabolites (Scheme 16) and tested for their aromatase inhibitory activity on human placental enzyme. While the [Ii ]-hydroxy isomer was the only competitive inhibitor of aromatase, the other two oxidized analogs, [I S]-hydroxy and 1-oxo-derivatives, had very weak inhibitory properties compared to PED (Ki 27 jjM and 12 juM vs 23 nM for PED and ty/, of 4 min and 2.16 min vs 10.4 min for PED) . These observations were in contrast to the a priori assumption that 10-(l-oxo-2-propynyl)estr-4-ene-3,17-dione might be the most active derivative in the series, due to its Michael acceptor structure i8,121 similarly, the 19-hydroxylated propargyl derivatives of 3-deoxyandrost-4-ene-17-one and androst-4-ene-3,6,17-trione were very weak mechanism-based inhibitors of aromatase ". ... 

Rea.ctlons, Propargyl alcohol has three reactive sites—a primary hydroxyl group, a triple bond, and an acetylenic hydrogen—making it an extremely versatile chemical intermediate. 

Various halogenating agents have been used to replace hydroxyl with chlorine or bromine. Phosphoms trihaUdes, especially in the presence of pyridine, are particularly suitable (17,18). Propargyl iodide is easily prepared from propargyl bromide by halogen exchange (19). 

Methylbutynol. 2-Methyl-3-butyn-2-ol [115-19-5] prepared by ethynylation of acetone, is the simplest of the tertiary ethynols, and serves as a prototype to illustrate their versatile reactions. There are three reactive sites, ie, hydroxyl group, triple bond, and acetylenic hydrogen. Although the triple bonds and acetylenic hydrogens behave similarly in methylbutynol and in propargyl alcohol, the reactivity of the hydroxyl groups is very different. 

This study demonstrates that the addition of the 2-diazopropane with the triple bond of propargyl alcohols is regioselective, and affords new antibacterial 3H-pyrazoles. The photochemical reaction of these 3H-pyrazoles selectively leads to a- and 6-hydroxy cyclopropenes. The overall transformation constitutes a simple straightforward route to substituted cyclopropenyl alcohols without initial protection of the propargyl alcohol hydroxyl group. 

The key feature of the first total synthesis of (+)-homopumiliotoxin 223G 418 was a Lewis acid-induced, chelation-controlled propargylation of the trifluoroacetate salt of (. )-2-acetyl pi peri dine 415, derived from iV-Cbz-L-pipecolinic acid. Alkyne 416 thus formed was transformed after several steps into 417, which was cyclized by activation of the primary hydroxyl with the carbon tetrabromide-triphenylphosphine system to give the natural product (Scheme 98) <1998TL2149>. 

Interestingly, the [RuCl2(p-cymene)]2 catalyst used for selective synthesis of (Z)-vinylsilanes produces instead the a-vinylsilanes with appropriately positioned hydroxyl groups.57 For the homopropargylic system shown (Scheme 12), the selectivity is 98 2. For propargylic or bishomopropargylic systems, only small amounts (2-13%) of the a-product... 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

On the other hand, unsymmetrical internal alkynes usually lead to two different constitutional isomers. In compounds of type 18, selectivity in favor of 20 rather than 19 is observed (1 20) owing to the hydroxyl groups which might direct the deprotonation by directing the base to the closer propargylic methylene protons (Scheme 1.8) [37]. This chelate-like behavior, of course, becomes less significant as the tether increases for 21 and 22 the yield is better but the selectivity is reduced to only 1 5. 

Metal-catalyzed substitution reactions involving propargylic derivatives have not been studied in much detail until recently [311, 312]. In this context, the ability shown by transition-metal allenylidenes to undergo nucleophilic additions at the Cy atom of the cumulenic chain has allowed the development of efficient catalytic processes for the direct substitution of the hydroxyl group in propargylic alcohols [313]. These transformations represent an appealing alternative to the well-known and extensively investigated Nicholas reaction, in which stoichiometric amounts of [Co2(CO)g] are employed [314-317]. 

Whereas the Markovnikov addition of carboxylic acids to propargylic alcohols produces P-ketoesters, resulting from intramolecular transesterification [30, 31], the addition to propargylic alcohols in the presence of Ru(methallyl)2(dppe) 1 at 65 °C leads to hydroxylated alk-l-en-l-yl esters via formation of a hydroxy vinylidene intermediate [32, 33]. The stereoselectivities are lo ver than those obtained from non-hydroxylated substrates. These esters, which are protected forms of aldehydes, can easily be cleaved under thermal or acidic conditions to give conjugated enals, corresponding to the formal isomerization products of the starting alcohols (Scheme 10.6). 

The oxidation of the primary hydroxyl groups in 3-phenyl-2-lV-acetylamino propanol and propargylic alcohol by electrogenerated chromic acid has been reported. jV-Acetylphenylalanin and propargylic acid are both formed in 90% current yield. 

Primarily noted for its ability to oxidize (hydroxylate) saturated ally lie, propargylic or cabon atom alpha to a carbonyl group. 

Hu S, Hager LP (1999) Highly Enantioselective Propargylic Hydroxylations Catalyzed by Chloroperoxidase. J Am Chem Soc 121 872... 

CPO catalyzes the oxidation of 2-alkynes to aldehydes in the presence of H202 or tBuOOH via an alcoholic intermediate as depicted in Scheme 2.18 [242]. Propargylic alcohols are rapidly oxidized to the corresponding aldehydes [243] and there is a report about highly enantioselective propargylic hydroxylations catalyzed by CPO [244], In addition, a number of primary alcohols are selectively oxidized to aldehydes in a biphasic mixture of hexane and a buffer (Scheme 2.18) [245, 246]. 

The direct substitution of hydroxyl groups can also be extended towards propargylic alcohols. In the presence of FeCl3, a plethora of O-, N- or S-nudeophiles are able to react with substituted propargylic alcohols [17]. Amongst the variety of nucleophiles, allylsilanes occupy an important position since this example resembles a cross-coupling reaction between an organometallic compound and an alcohol (Scheme 7.12) [17]. 

The chemical properties and uses of propargyl alcohol has three potentially reactive sites (1) a primary hydroxyl group (i.e., CH2OH), (2) a triple bond (-C=C-), and (3) an acetylenic hydrogen (-C=CH) that makes the alcohol an extremely versatile chemical intermediate. The hydroxyl group can be esterified with acid chlorides, anhydrides, or carboxylic acids, and it reacts with aldehydes or vinyl ethers in the presence of an acid catalyst to form acetals. At low temperatures, oxidation with chromic acid gives propynal or propynoic acid ... 

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