Alkynyl alcohols synthesis

Asymmetric synthesis of stavudine and cordycepin, anti-HIV agents, and several 3 -amino-3 -deoxy-P-nudeosides was achieved utilizing this cycloisomerization of 3-butynols to dihydrofuran derivatives [16]. For example, Mo(CO)6-TMNO-promoted cyclization of the optically active alkynyl alcohol 42, prepared utilizing Sharpless asymmetric epoxidation, afforded dihydrofuran 43 in good yield. Iodine-mediated introduction of a thymine moiety followed by dehydroiodination and hydrolysis of the pivaloate gave stavudine in only six steps starting from allyl alcohol (Scheme 5.13). 

The rhodium-catalysed addition of alkynes to 1,2-diketones, 1,2-keto esters, and aldehydes has provided a method for the synthesis of tertiary alkynyl alcohols under... 

The trans allylic alcohol needed to make this compound was made using one of the methods we introduced in Chapter 3i reduction of an alkynyl alcohol with LiAlEL]. Here is the full synthesis alkylation of an ester enolate with prenyl bromide gives a new ester, which itself is turned into an alkylating agent by reduction and tosylation. The alkyne is introduced as its lithium derivative with the alcohol protected as a THP acetal. Hydrolysis of the acetal with aqueous acid gives the hydroxy-alkyne needed for reduction to the E double bond, which is then epoxidized. 

A one-pot synthesis of benzolactones and lactams via a cobalt-catalyzed regioselective [2-f2-f2] co-cyclotrimeriza-tion of alkynyl alcohols and amines with methyl propiolate has been described (Equation 54) <2005CC4955>. 

Some other alkynylcerium reagents have been generated and used for the synthesis of alkynyl alcohols and related compounds in good yields. An example is illustrated in Scheme 23. 

Furthermore, optically active alkynyl alcohols, useful intermediates for the synthesis of several optically active natural products, were obtained by the asymmetric addition of lithium acetylides to aldehyde in the presence of chiral ligand 2a Enhanced enantioselectivity in this reaction depends apparently on the substituent group in the acetylene moiety. As shown in Table 8, use of trialkylsilylacetylides gave the best results Various optically active ethynyl alcohols were obtained by the reaction of lithium trimethylsilylacetylide with aliphatic aldehydes, as summarized in Table 9... 

The alkynyl alcohols are successfully converted to y-ethyl-y-butyrolactone, an insect pheromone of Trogoderma, and (R)-5-octyI-2[5H]-furanone, an important synthetic intermediate for the synthesis of naturally occurring avenaciolide (Scheme 4)... 

As with cyanide, Sn2 reactions of alkyne anions can be done with substrates other than halides or sulfonate esters. Epoxides are opened by acetylides at the less sterically hindered carbon to give an alkynyl alcohol. A synthetic example is the reaction of epoxide 38 with the indicated lithium alkyne anion gave an 85% yield of 39, an intermediate in the Sinha et al. synthesis of squamotacin.49... 

The other major synthetic use of alkyne anions is their reaction with ketones and aldehydes to give an alkynyl alcohol via nucleophilic acyl addition. The lithium salt of 1-propyne, for example, reacted with aldehyde 40 to give alcohol 41 as part of Smith s synthesis of (+)-acutiphycin.50 The reaction is selective for ketones and aldehydes in the presence of acid derivatives, if the acetylide is not present in large excess. l... 

Another synthesis of D-oUvose derivative exploited a tungsten carbonyl catalyzed alkynyl alcohol cycloisomerization reaction [54,55]. This useful method allows for synthesis of variety of glycals from an achiral precursor (35), which after enantioselective reduction and Sharpless epoxidation afforded intermediates 39 and 42 (by Mitsunobu inversion), precursors of unnatural D-rhamnal (40) and valuable L-fucal (43) derivatives, respectively (Scheme 4). 

Synthesis of Indoles from Aminoalcohol and Alkynyl Alcohols by Ir-Pt Catalyst... 

My first paper in chemoenzymatic synthesis appeared in the fall of 1978 under the title "Synthesis of optically active alkynyl alcohols by microbial asymmetric hydrolysis of the corresponding acetates" [2,3]. As shown in Figure 24.1, asymmetric hydrolysis of ( )-l with Bacillus subtilis var. niger was only moderately successful, yielding the recovered (1 )-1 and the hydrolyzed (S)-2 of 7-96% ee [2, 3]. After 35 years of cooperative endeavor by biochemists as the suppliers of enz5unes and synthetic chemists as the users, it is now possible to employ various lipases and esterases as commercially available and bottled reagents for enantioselective synthesis of natural products, pharmaceuticals, and agrochemicals. 

Terminal-functionalized polymers such as macromonomers and telechelics are very important as prepolymer for construction of functional materials. Single-step functionalization of polymer terminal was achieved via lipase catalysis. Alcohols could initiate the ring-opening polymerizahon of lactones by lipase catalyst. The lipase CA-catalyzed polymerizahon of DDL in the presence of 2-hydroxyethyl methacrylate gave the methacryl-type polyester macromonomer, in which 2-hydroxyethyl methacrylate acted as initiator to introduce the methacryloyl group quanhtatively at the polymer terminal ( inihator method ).This methodology was expanded to the synthesis of oo-alkenyl- and alkynyl-type macromonomers by using 5-hexen-l-ol and 5-hexyn-l-ol as initiator, respechvely. 

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