Amine with allyl vinyl ethers

REPPE PROCESS. Any of several processes involving reaction of acetylene (1) with formaldehyde to produce 2-butync-l,4-diol which can be converted to butadiene (2) with formaldehyde under different conditions to produce propargyl alcohol and, form this, allyl alcohol (3) with hydrogen cyanide to yield acrylonitrile (4) with alcohols to give vinyl ethers (5) with amines or phenols to give vinyl derivatives (6) with carbon monoxide and alcohols to give esters of acrylic acid (7) by polymerization to produce cyclooctatetraene and (8) with phenols to make resins. The use of catalysis, pressures up to 30 atm, and special techniques to avoid or contain explosions are important factors in these processes. 

A more concise route to ( )-cherylline was also devised and commenced with the reductive animation of isovanillin with methylamine followed by reaction of the intermediate benzylamine with vinyl triphenylphosphonium bromide to provide the aminophosphonium salt 619. Sequential treatment of 619 with n-butyllithium and the quinone ketal 615 followed by reaction of the resulting crude allylic amine 620 with boron trifluoride etherate gave the phenolic amine 618 in good overall yield (225). 

Allylic double bonds can be isomerized by some transition metal complexes. Isomerization of alkyl allyl ethers 480 to vinyl ethers 481 is catalysed by Pd on carbon [205] and the Wilkinson complex [206], and the vinyl ethers are hydrolysed to aldehydes. Isomerization of the allylic amines to enamines is catalysed by Rh complexes [207]. The asymmetric isomerization of A jV-diethylgeranylamine (483), catalysed by Rh-(5)-BINAP (XXXI) complex to produce the (f )-enaminc 484 with high optical purity, has been achieved with a 300 000 turnover of the Rh catalyst, and citronellal (485) with nearly 100% ee is obtained by the hydrolysis of the enamine 484 [208]. Now optically pure /-menthol (486) is commerically produced in five steps from myrcene (482) via citronellal (485) by Takasago International Corporation. This is the largest industrial process of asymmetric synthesis in the world [209]. The following stereochemical corelation between the stereochemistries of the chiral Rh catalysts, diethylgeranylamine (483), diethylnerylamine (487) and the (R)- and (5)-enamines 484... 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

Olefination of the aldehyde of 196 installed an additional carbon necessary for advancement to the natural products, giving methyl vinyl ether 197. Treatment with dimethyldioxirane at low tenperature acconplished oxidation at sulfur in the presence of the electron-rich vinyl ether, and the resulting sulfoxides (mixture of diastereomers at sulfur) underwent high-yielding Mislow-Evans rearrangement to allylic alcohol 198 under mild conditions in methanol containing trimethylphosphite and di-zso-propyl amine. The product 198 of this sequential Claisen/Mislow-Evans process was converted to either (-)-joubertinamine or (-)-mesembrine in a short series of steps. 

---