Hydroxylation alkynes

Very recently, Monteiro and Jia [85] reported a thiol-ene reaction for the preparation of cyclic polymer with inherent alkyne functionality from RAFT polymerization. An alkyne-hydroxyl-RAFT agent, through post-polymerization functionalization, was used to introduce an acrylate to the polymer via the reaction of the hydroxyl group with acryloyl chloride. Through the successive aminolysis of the RAFT and thiol-ene reaction between the acrylate group and thiol group, which was generated from aminolysis under hexylamine, alkyne functional monocyclic PSTY, PDMA, PNIPAM, and P BA were obtained (Scheme 37). 

The reaction works for aldehydes and ketones, aromatic or aliphatic or conjugated, and tolerates functional groups such as alkene, alkyne, hydroxyl, ester, ether, acetal, ArNOj, halogen, and... 

By analogy to the hydration of alkenes hydration of an alkyne is expected to yield an alcohol The kind of alcohol however would be of a special kind one m which the hydroxyl group is a substituent on a carbon-carbon double bond This type of alcohol IS called an enol (the double bond suffix ene plus the alcohol suffix ol) An important property of enols is their rapid isomerization to aldehydes or ketones under the condi tions of their formation... 

Among the tasks remaining is the replacement of the C-16 hydroxyl group in 16 with a saturated butyl side chain. A partial hydrogenation of the alkyne in 16 with 5% Pd-BaS04 in the presence of quinoline, in methanol, followed sequentially by selective tosylation of the primary hydroxyl group and protection of the secondary hydroxyl group as an ethoxyethyl ether, affords intermediate 17 in 79% overall yield from 16. Key intermediate 6 is formed in 67 % yield upon treatment of 17 with lithium di-n-butylcuprate. 

With the exocyclic alkylidene at C-13 properly in place, the elaboration of the l,5-diyn-3-ene moiety can now be addressed. Cleavage of both acetate and trimethylsilyl functions in 86 with basic methanol, followed by triethylsilylation of the newly formed tertiary hydroxyl group, efficiently affords alkyne 25 (86 % overall yield). This substance was regarded as a viable candidate for a Pd-catalyzed coupling reaction.12 Indeed, treatment of 25 with (Z)-chloroenyne 26 in the presence of a catalytic amount of Pd(PPh3)4 and Cu1 results in the formation of enediyne 24 in 91 % yield. 

The generality and functional group compatibility were also excellent with regard to the alkynes (Table 2). Free hydroxyl groups and even a remote double bond were compatible and give very good yields and purities. 

The anti-Markovnikov product was formed with >95% regioselectivity at 35°C. The examples in Scheme 5-21, Eq. (1) show that cyano and hydroxyl functional groups are tolerated by the catalyst, and diphenylphosphine oxide can be added to both C=C bonds in a di-alkyne. The reaction also worked for internal alkynes (Scheme 5-21, Eq. 2). Unusual Markovnikov selectivity was observed, however, for 1-ethynyl-cyclohexene (Scheme 5-21, Eq. 3) [17]. 

Pal et al. explored an efficient Pd/C-catalyzed reaction of 2-iodophenols with terminal alkynes in water without the use of any organic cosolvents in the presence of PPh3, Cul, and prolinol to give the expected benzofuran products (Eqs. 4.42, 4.43).78 The hydroxyl group was well tolerated during reactions. When used as a base, prolinol afforded better yields of products than triethylamine, a common organic base, possibly due to its better miscibility with water. 

Trost and coworkers [131] synthesized oxaheterocycles by a Pd-catalyzed addition of terminal alkynes onto hydroxyalkynoates, followed by an intramolecular addition of the hydroxyl functionality on the triple bond. Simple lactonization may take place as a side reaction. 

Fiirstner and coworkers developed a new Pt- and Au-catalyzed cycloisomerization of hydroxylated enynes 6/4-141 to give the bicylo[3.1.0]hexanone skeleton 6/4-143, which is found in a large number of terpenes [317]. It can be assumed that, in the case of the Pt-catalysis, a platinum carbene 6/4-142 is formed, which triggers an irreversible 1,2-hydrogen shift. The complexity of the product/substrate relationship can be increased by using a mixture of an alkynal and an allyl silane in the presence of PtCl2 to give 6/4-143 directly, in 55 % yield (Scheme 6/4.36). 

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>. 

The synthetic approach to the benzo[fo]furan is similar to that of the thiophenes described in Scheme 39. The synthetic approach was described by Flynn et al. [73], and an example synthesis is given in Scheme 40. The appropriate iodophenol 104 is coupled to the aryl alkyne 111. The intermediate 155 is subsequently cyclized in the presence of an appropriately substituted aryl iodide, e.g., 107 under an atmosphere of carbon monoxide gas, to give the benzo[fr]furan chalcone derivative 156. Deprotection of the hydroxyl produces the target compound 157. 

The palladium-catalyzed C-Se bond formation79-81 and the platinum-catalyzed carboselenation of alkynes with selenoesters have been reported in analogy with the thiolate chemistry. An electron-withdrawing or electron-donating group on the aromatic residue leads to the formation of the desired carboselenation product with acceptable yields. Functionalities like benzyl, hydroxyl, or nitrile group are tolerant with the reaction conditions. This method provides a new access to the functionalized vinylselenide 60,82 molecules of interest as key intermediate (Scheme 19) 85... 

Carbo-oxylation (carbohydroxylation and carboalkoxylation), whereby an organic group and an oxy (hydroxyl or alkoxy) group add across a carbon-carbon double bond or a triple bond, is an important transformation in organic synthesis. We found that the reaction of a cation pool with an alkene or alkyne followed by the trapping of the resulting carbocation by water led to the... 

Some interesting modifications with respect to the base-induced isomerization have recently been developed. For example, conversion of 4-hydroxy-l-thiophenyl-2-alkynes 299 into the corresponding 4-hydroxy-substituted thiophenylallenes 300 was achieved by treatment with potassium hexamethyldisilazide at low temperature (Scheme 8.79) [165], If the hydroxyl group is protected as the THP ether an elimination reaction occurred, resulting in the formation of an enyne instead of allene 300. 

A combination of RuH2(PPh3)4 and ferrocenylphosphines catalyzes the crosscoupling reaction of a-hydroxyallenes and 1-alkynes to give exo-enynes selectively (Scheme 16.96) [102]. From the observation that O-protected allenes and 5-phenyl-1,2-pentadiene are inert to the cross-coupling reaction, the a-hydroxyl group in allenes plays an important role in this exo-selective reaction. 

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. 

The analogous hydroxylation of alkynes to produce ketones is enhanced by the co-catalytic effect of Aliquat and platinum(IV) chloride-carbon monoxide [3] it is assumed that HPtCI(CO) is the active hydration species. C-S and C-Br bonds are cleaved under the reaction conditions. 

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