Allyl chloride enol ether preparation

The cyclic enol ether 255 from the functionalized 3-alkynoI 254 was converted into the furans 256 by the reaction of allyl chloride, and 257 by elimination of MeOH[132], The alkynes 258 and 260, which have two hydroxy groups at suitable positions, are converted into the cyclic acetals 259 and 261. Carcogran and frontalin have been prepared by this reaction[124]. 

The same strategy has been used by Williams (90JA808) in his synthesis of brevianamide B. The aldehyde (82), prepared enantioselectively from L-proline, was converted to the silyl ether. Acylation of this (BuLi, ClC02Me) gave the carbomethoxy derivative as a mixture of diastereo-mers, which was alkylated by gramine. As before, an enolate alkylation (Sn2 ) on an allyl chloride derived from the above gave the tricyclic compound, which could be transformed to brevianamide B (Scheme 24). 

Allyl silanes react with a wide variety of electrophiles, rather like the ones that react with silyl enol ethers, provided they are activated, usually by a Lewis acid. Titanium tetrachloride is widely used but other successful Lewis acids include boron trifluoride, aluminium chloride, and trim ethyls ilyl tri-flate. Electrophiles include the humble proton generated from acetic add. The regiocontrol is complete. No reaction is observed at the other end of the allylic system. All our examples are on the allyl silane we prepared earlier in the chapter. 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

The enol precursor 151 was prepared in three steps by addition of Steri-col 150 onto trichloroethylene, which was followed by the formation of a sensitive ynol through addition of n-BuLi and excess allyl iodide (Scheme 43). The ynol was then partially hydrogenated with Pd on barium sulfate, furnishing the required enol ether 152 contaminated with 8% of the corresponding dihydro enol ether. [2+ 2]-Cycloaddition between 152 and dichloroketene, generated in situ from trichloroacetyl chloride, led to the cyclobutanone 153 as the major diastereomer with a 93 7 diastereocontrol. 

Enol ethers are prepared by acid-catalyzed transesterification or transetherification from other enol ethers, orthoesters, ketone acetals and similar precursors with allyl alcohol. The intermediate isopyrocin (the same holds for pyrocin) [48] is cleaved with thionyl chloride to afford the substrate 35 for cyclizing 1,3-elimination (Reaction scheme 21) in the presence of base [49] without significant P-elimination. 

Cross-coupling reactions leading to the formation of C-X (X = heteroatom) bonds catalyzed by Pd(dba)2 have been reported. Aniline derivatives have been prepared via reaction of amine nucleophiles with aryl halides in the presence of Pd(dba)2 and phosphines, especially P( Bu)3. Likewise, diaryl and aryl alkyl ethers are produced from aryl halides (Cl, Br, I) and sodium aryloxides and alkoxides under similar conditions. Conditions effective for the coupling of aryl chlorides with amines, boronic acids, and ketone enolates using an easily prepared phosphine chloride as a ligand have recently been uncovered (eq 22). The preparation of aryl siloxanes and allyl boronates via Pd(dba)2-catalyzed C-Si and C-B coupling have been reported as well. 

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