Epoxides with acetylides

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

The ring opening of epoxides with carbon nucleophiles represents a Scheme 2.21 useful way of making C-C bonds. Grignard, organolithium and organocopper reagents and alkali metal acetylides have all been used for this purpose. This type of reaction has been used to form carbocyclic systems. 

The proton of terminal acetylenes is acidic (pKa= 25), thus they can be deprotonated to give acetylide anions which can undergo substitution reactions with alkyl halides, carbonyls, epoxides, etc. to give other acetylenes. 

Starting from 3,4,6-tri-O-benzyl-D-glucal epoxide 93 (Scheme 31), a-C-glycosyl compounds 94 are obtained in good stereoselectivity by treatment with a lithium acetylide and zinc chloride.103... 

Ethyl 2,3-epoxypropanoate is a very interesting chiron. It may be opened by various organometallic compounds such as dialkyl, diaryl, and divinyl lithium cuprates, dialkylmagnesium cuprates, trialkylalanes and aluminum acetylides.5 6 The epoxide ring is attacked regiospecifically at the p-position and produces a-hydroxy esters exclusively without racemization. The same result is observed with... 

A second approach (472) to 512 started with trans-2-buitnc epoxide (524) (Scheme 67). Opening of the epoxide ring of 524 with lithium acetylide gave an acetylenic alcohol, which was converted to the acetylenic acid (525) by carbox-ylation with gaseous carbon dioxide. Partial hydrogenation of 525 followed by lactonization afforded the a,3-unsaturated lactone (526) which was transformed to the nitrolactone (527) by a Michael addition reaction of nitromethane. The Nef reaction of 527 gave the tetrahydrofuranyl acetal (528) which was converted to... 

Excellent yields can be obtained when the mixture of RC=CLi and the epoxide in ammonia is allowed to stand for 12 to 24 hours [2]. With sodium acetylides, there is some risk of subsequent attack of the acetylenic alcoholate on the epoxide, especially when the latter compound is used in excess. The reaction of acetylenic magnesium halides, RCsCMgX, with epoxides also leads to homopropargylic alcohols, but this is generally not recommended as a satisfactory method, as impure products are often obtained [62], Coordination of the epoxide-oxygen atom with the Lewis acid may give rise to a Sjql-like attack of RCaC on... 

In the presence of (a sufficient amount of) DMSO or HMPT, alkali acetylides react smoothly and cleanly with epoxides to give the desired alcohols [2],... 

Diels-Alder reactions of a -ethenylidenecyclanonesJ These dienophiles (1) are readily obtained by reaction of lithium acetylide with epoxides followed by oxidation, but tend to polymerize when heated. Fortunately catalysts, such as BF3 etherate or ZnCl2, permit Diels-Alder reactions to proceed at low temperatures. This cycloaddition provides a regio- and stereoselective route to spirocylic dienones (2) in fair to good yield. 

Silver acetylides also reacted with epoxides yielding propargylic alcohols.27 As for related alkylations with silver acetylides (see Section 10.6.1), this reaction required zirconocene dichloride and catalytic amount of silver triflate. This method proved useful for both electron-rich and electron-deficient alkynes and compatible with various acid- and base-sensitive functional groups (Table 10.2). 

TABLE 10.2. Epoxide Opening with Silver Acetylides... 

Since such reactivity has recently been reviewed,8 only a few examples are reported here. Acyl halides or epoxides can be alkynylated with preformed silver acetylides. Such processes have been applied to the total synthesis of the antibiotic macrolide (+ )-methynolide,96 and in the total synthesis of the antitumor agent FR901464 isolated from a Pseudomonas species (Scheme 10.62).97... 

Cuprates derived from compound 604 and Cul911,912 or from copper acetylide and compound 605913,914 underwent alkylation with epoxides. 

Of course, one could also think about opening the epoxide 33 with lithium acetylide to the enyne 38, which could eventually be further reacted by Trost s method (e.g. with the vinyl bromide 27). 

Terminal alkynes are readily converted to acetylide anions with strong base. These anions are strong nucleophiles, capable of reacting with electrophiles such as alkyl halides and epoxides. 

A Sn2 reaction of an alkyl halide with an acetylide anion, C=CR 11.11B Opening of an epoxide ring with an acetylide anion, C=CR... 

This interesting result may be rationalized by transmetallation with ZnCl2 of the lithium acetylide to 23 and formation of an alkynyl-zinc complex 24 with the 1,2-epoxide 15... 

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