Ethers, acetylenic cleavage

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield.Under these cleavage conditions i,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, r-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

As with alkenes we consider first those oxidations which do not cleave the acetylenic bond giving a-diketones, or oxidation of alkynyl amines and ethers to a-keto amides and esters, and then consider oxidative alkyne cleavage to acids. 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

Solutions of these metals in liquid ammonia effect (i) the reduction of a range of functional groups such as carbonyl and acetylenic and also conjugated and aromatic systems, and (ii) cleavage of benzyl and allyl ethers and thioethers. These reactions are usually carried out by the general procedure of adding the metal to a solution of the substrate in liquid ammonia to which dry methanol or ethanol or t-butanol has been added to provide a ready proton source (alcohols are more acidic than ammonia).34... 

RC = CCH,X — RCX = C==CH,. /S.y- and 7,S-Acetylenic alcohols can be transformed to the halides in better yields by an alternative procedure, which consists in their esterification with p-toluenesulfonyl chloride and subsequent cleavage of the ester by the action of sodium iodide, lithium chloride, or calcium bromide in an appropriate solvent (60-90%). Halo ethers are prepared by the action of phosphorus tribromide on hydroxy ethers, as in the preparation of /3-ethoxyethyl bromide (66%). In a similar manner, /3-halo esters have been prepared without appreciable dehydration of the /3-hydroxy ester (40-60%). The reaction of cyanohydrins leads to a-halo nitriles. Treatment of 2-nitro-l-propanol with phosphorus pentachloride gives l-chloro-2-nitropropane (47%). ... 

Stereospecific synthesis of 1,3-dienes. Corey et a .3 have described a new synthesis of 1,3-dienes based on the highly stereospecific cis addition of alkylcopper reagents to a, -acetylenic carbonyl compounds (3, 108). Thus the reaction of methyl 4-trimethyl-siloxy-2-nonynoate (l)4 in THF with divinylcopperlithium (1.25 eq) at —90° and then at — 78° affords the pure e(r adduct (2) in > 90% yield. Treatment of (2) with methanolic hydrochloric acid effects cleavage of the trimethylsilyl ether and lactonization to give (3). 

Photolysis at 365 nm in CH3CN improves the rate of DDQ promoted cleavage of benzyl ethers in that under these conditions cleavage occurs at rt. The MPM groups is still cleaved more rapidly and good selectivity can be achieved over benzyl ether cleavage. Unfortunately, olefins and acetylenes are incompatible with this protocol." ... 

Acetylenic cobalt complexes greatly facilitate the heterolytic cleavage of adjacent alcohols or ethers. On treatment with Lewis acids, these complexes afford cobalt stabilized carbenium ions, which can be captured by nucleophiles such as enolates. Jacobi and Zheng have employed chiral boron enolates of Evans s oxa-zolidinone 6.91 (R = i-Pr). After removal of the chiral auxiliary, they obtained anti adds 11.43 with a high selectivity [1677] (Figure 11.9). The reaction can be extended to the boron enolates of related oxazolidinones and to a-branched propargyl derivatives. This reaction has been applied to the synthesis of P-aminoacids after Curtius rearrangement and oxidation of the triple bond [1677]. 

Another approach to carrying out tin-free radical fragmentation processes, developed by Fuchs, utilizes trifluoromethyl sulfone, or triflone, derivatives. Fuchs first reported examples of free radical alkynylation reactions using acetylenic triflone 102 [62]. What is most remarkable about these reactions is that the radicals being alkynylated are formed from the cleavage of C-H bonds standard radical precursors are not required. For example, when tetrahydrofuran is mixed with triflone 102 at room temperature, alkynylation occurs a to the ether oxygen in 92% yield (Scheme 21). In this case, the radical chain process is most likely initiated by traces of peroxides in the THF. Similarly, unactivated alkanes such as cyclohexane will react with triflone 102 in good yield (83% for cyclohexane) when heated with a catalytic amount of AIBN. 

With this key union effected, only a few operations separated 48 from the substrate needed to test enyne metathesis (i.e. 12, Scheme 9). First, the controlled exposure of this compound (48) to 2 equivalents of TBAF in THF at 0°C effected the lysis of both the phenolic silyl ether and the TMS group append onto the terminal position of the alkyne, but, importantly, not the TIPS group on the other acetylene group. As such, in the next operation partial reduction with Lindlar s catalyst (Pd on BaS04 poisoned with quinoline) was accomplished selectively on only one alkyne to provide the needed terminal olefin. Finally, cleavage of the alky-nyl TIPS moiety under more forcing conditions (TBAF, THF, 25 °C), followed by silylation of both the allylic hydroxy and the phenolic groups (TBSCl, imid, DMF), then completed the assembly of enyne metathesis precursor 12 in 62% overall yield from 48. 

An improved method has been described for the preparation of glyoxylic acid esters by oxidative cleavage of the corresponding tartrates use of ethereal periodic acid necessitates no work-up procedure, obviating the problem of water solubility of the lower glyoxylates. j8-Keto-csters are dehy ated to the corresponding acetylenic esters by oxidation of the derived 5-pyrazolones with thallium(in) nitrate (Scheme 36). 

The reaction of a,co-diyne with monoene instead of monoyne also gave an aromatic compound (Scheme 5.4) [9], The reaction included cleavage of a C—O bond. Diyne 7 reacted with 50 equiv of 2,3-dihydrofuran to give aromatic alcohol 8 in 97% yield. Acyclic vinyl ether such as n-butyl vinyl ether could be used in place of 2,3-dihydrofuran. The reaction of 7 with 25 equiv of n-butyl vinyl ether gave 9 and 10. The combined yield was nearly quantitative. n-Butyl vinyl ether acted as an acetylene equivalent when the reaction gave 9. Based on this result, an enol ether could be used as an acetylene equivalent in Rh-catalyzed [2 -j- 2 -j- 2] cycloaddition [11]. 

---