A method of making spirogalbanone includes the steps of: (a) subjecting ethynylspirodecanol to a Rupe rearrangement to give a compound of the formula I

##STR00001## (b) converting the compound of (a) to a C1-C4 alkyl acetal; (c) subjecting the acetal to a trans-acetalisation reaction with allyl alcohol in the presence of a mild acid catalyst; (d) heating the product of (c) in the presence of an acid catalyst to give an allylenolether; and (e) subjecting the product of (d) to a Claisen rearrangement to give spirogalbanone.

The method affords an easier and more efficient method of preparation.

The invention relates to improved method of synthesis for Treprostinil comprising condensation reaction of the carbonyl compound having allyl, alkyl, crotyl or MEM-protected phenolic hydroxyl group, compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gave the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents was governed by protecting groups, gave the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yielded the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts, having desired purity.

The invention relates to improved method of synthesis for Treprostinil comprising condensation reaction of the carbonyl compound having allyl, alkyl, crotyl or MEM-protected phenolic hydroxyl group, compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gave the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents was governed by protecting groups, gave the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yielded the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts, having desired purity.

Provided are methods for the meta-selective CH arylations of arene alcohol-based substrates. The methods combine the transient norbornene strategy with a quinoline-based acetal scaffold to achieve the formation of biaryl compounds. These processes establish a foundation for catalytic polyfunctionalization of alcohol-based compounds. The method comprises attaching a heterocyclic hemiacetal scaffold to an aromatic alcohol or a substituted aromatic alcohol; reacting the aromatic or substituted aromatic alcohol having the heterocyclic hemiacetal scaffold attached with an alkyl or aryl iodide in a reaction mix comprising a palladium catalyst, a silver salt, and carboxymethyl norbornene to generate a meta-arylated arene conjugated to the heterocyclic hemiacetal scaffold; and then cleaving the heterocyclic hemiacetal scaffold from the meta-arylated arene alcohol.

Provided are methods for the meta-selective CH arylations of arene alcohol-based substrates. The methods combine the transient norbornene strategy with a quinoline-based acetal scaffold to achieve the formation of biaryl compounds. These processes establish a foundation for catalytic polyfunctionalization of alcohol-based compounds. The method comprises attaching a heterocyclic hemiacetal scaffold to an aromatic alcohol or a substituted aromatic alcohol; reacting the aromatic or substituted aromatic alcohol having the heterocyclic hemiacetal scaffold attached with an alkyl or aryl iodide in a reaction mix comprising a palladium catalyst, a silver salt, and carboxymethyl norbornene to generate a meta-arylated arene conjugated to the heterocyclic hemiacetal scaffold; and then cleaving the heterocyclic hemiacetal scaffold from the meta-arylated arene alcohol.

Provided are methods for the meta-selective CH arylations of arene alcohol-based substrates. The methods combine the transient norbornene strategy with a quinoline-based acetal scaffold to achieve the formation of biaryl compounds. These processes establish a foundation for catalytic polyfunctionalization of alcohol-based compounds. The method comprises attaching a heterocyclic hemiacetal scaffold to an aromatic alcohol or a substituted aromatic alcohol; reacting the aromatic or substituted aromatic alcohol having the heterocyclic hemiacetal scaffold attached with an alkyl or aryl iodide in a reaction mix comprising a palladium catalyst, a silver salt, and carboxymethyl norbornene to generate a meta-arylated arene conjugated to the heterocyclic hemiacetal scaffold; and then cleaving the heterocyclic hemiacetal scaffold from the meta-arylated arene alcohol.

A method of preparing ortho-alkenyl and ortho-acetyl benzylic alcohols is disclosed.

A method of preparing ortho-alkenyl and ortho-acetyl benzylic alcohols is disclosed.

A polyether diol compound represented by the following formula (3): ##STR00001##
where R.sup.5, R.sup.6, R.sup.7 and R.sup.8, which may be the same as or different from each other, each represent a linear or branched alkyl group having 1 to 6 carbon atoms.

A polyether diol compound represented by the following formula (3): ##STR00001##
where R.sup.5, R.sup.6, R.sup.7 and R.sup.8, which may be the same as or different from each other, each represent a linear or branched alkyl group having 1 to 6 carbon atoms.