Propargyl alcohols, building block

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

Smith has employed a related process using the ligand 3 developed by Jiang to obtain a chiral propargyl alcohol. This served as a key building block in an elegant synthesis of (-)-indolizidine 223AB (Eq. 21) [26],... 

In this synthesis (Scheme 6), the C2-symmetri-cal triacetonide of D-mannitol (32) is converted via the epoxide 33 and its nucleophilic addition product 34 to the propargylic alcohol derivative 35. From this intermediate, the Z-configured vinyl iodide 36 is stereoselectively obtained by hydroalumination/iodination. The Pd-catalyzed Heck cyclization then affords the isomerically pure product 37, which represents a potential building block for the synthesis of la,2y5,25-trihy-droxy-vitamin D, following the classical Wittig strategy of Lythgoe. 

In addition, the highly enantioenriched propargylic alcohols obtained in such a way are versatile building blocks. Theyhave been applied to the syntheses of the alkyl side chains of zaragozic acids A and C,"several metabolites isolated from marine sponges, and the octalactin A ring. ... 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

With a similar perspective aimed at unravelling enzymatie proeesses involving nucleic acids, Beal reported the synthesis of novel phosphoramidite for incorporation in 7-substituted-8-aza-7-deazaadenosine derivatives (36a-d) into RNA to examine the RNA-editing adenosine deaminase SAR. The 8-aza-7-deazaadenosine building block was found to be an excellent substrate while functionalisation of the C-7 hydrogen with bromine, iodine or propargyl alcohol resulted decreased rates of catalysis. 

Gold nanoparticles on ZnO were used as a catalyst for the rapid one-pot three-component condensation of amines (106), aldehydes (107), and phenyl acetylene (20), affording the selective synthesis of propargylamines (108) at room temperature (Scheme 9.32) (Gonzalez-Bejar et al. 2013). Propargylic alcohols constitute important building blocks for many biologically active compounds and natural products. 

The above approaches can also be applied to a range of other aromatic heterocycles, including furans, thiophenes and oxazoles [2, 15]. While these protocols typically require the initial assembly of the precursor for cyclization, Trost has demonstrated that palladium catalysis can also be employed to assemble the en-yn-ol 8 for cyclization to furans. (Scheme 6.11) [16]. This reaction, that proceeds via the palladium-catalyzed regioselective addition of terminal alkynes to internal propargyl alcohols, provides a biomolecular method to build up furans from these two alkyne building blocks. 

In early 2015, Loh and co-workers achieved an elegant Cu(0)- or Co(0)- catalyzed three component oxidative coupling of 1,3-enynes (or styrenes), simple alcohols, and TBHP (Scheme 2.19) [99]. The resulting P-peroxy alcohols and P-hydroxyketones are important building blocks. They can further be transformed into p-hydroxyynones and propargylic 1,3-diols. 

Propargylic alcohols, which possess inherent alkynyl and hydroxyl functional groups, are one of the most valuable bifunctional building blocks in the field of organic synthesis. Very recently, Zhan and co-workers described the synthesis of substituted pyrazoles 40 via AgOTf-catalyzed cascade propargylic... 

The second key building block, phosphonium salt 172, was prepared as outlined in Scheme 3.39. Iodide 163 was reacted in a copper(I)-catalyzed alkylation with the bisbromo-magnesium salt 164 to give triyne 165 in 90% yield. Reduction of the propargylic alcohol 165 to allylic alcohol 166 was achieved with lithium aluminum hydride (LAH), and then a... 

The mono- and dianions of [ C2]acetylene, readily accessible by deprotonation with n-BuLi (1 equivalent) and MeLi (2.5 equivalents), respectively, can be trapped with monomeric formaldehyde to give [2,3- C2]propargyl alcohol in 40% yield and 2-[2,3- C2]butyne-l,4-diol in 72% yield. Both compounds may serve as valuable intermediates for the preparation of additional low-molecular weight building blocks and intermediates. [2,3- C2]propargyl alcohol, for example, can be reduced with aqueous CrCl2 to [2,3- C2]allyl alcohol, which was shown to be activated through tosylate formation toward nucleophilic displacement of the hydroxy function to produce radio-... 

There have been significant discoveries of methods that enable the enantioselective addition of an alkyne to an aldehyde or a ketone [182]. The resulting chiral propargyl alcohols are amenable to a wide variety of subsequent structural modifications and function as useful, versatile chemical building blocks. In 1994, Corey reported the enantioselective addition reactions of boryl acetylides such as 292, prepared from the corresponding stannyl acetylenes (e.g., 291) in the presence of the oxazaborolidine 293 as the chiral catalyst (Scheme 2.36) [183]. Both aliphatic and aromatic aldehydes were demonstrated to participate in these addition reactions, which proceeded in high yields and with impressive enantioselectivity. The proposed transition state model 295 is believed to involve dual activation both of the nucleophile (acetylide) and of the electrophile (aldehyde). The model bears a resemblance to the constructs previously proposed for alkylzinc addition reactions (Noyori, 153) and borane reductions (Corey. 188). 

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