Direct conversion of benzylic and allylic alcohols to phosphonates

Benzyl phosphonate esters often serve as reagents in Horner-Wadsworth-Emmons reactions. In most cases, they can be prepared from benzylic alcohols via formation of the corresponding halide followed by an Arbuzov reaction. To identify a more direct synthesis of phosphonate esters, we have developed a one-flask procedure for conversion of benzylic and allylic alcohols to the corresponding phosphonates through treatment with triethyl phosphite and ZnI(2).     

Improved synthesis of isocarbacyclin using regioselective alkylation of allylic alcohols

Two efficient syntheses of isocarbacyclin (1) have been realized using highly regioselective direct alkylation of both - and -allylic alcohols (2 and 3)     

Stepwise conversion of oxiranes to allylic alcohols by iodotrimethylsilane and DBU

Iodotrimethylsilane, prepared from hexamethyldisilane and iodine reacts smoothly with oxiranes to give (2-iodoalkoxy)trimethylsilanes which can be converted to allylic alcohols with DBU in good yields. The whole conversion can be carried out in one-pot operation.     

Highly efficient, catalytic bis addition reactions of allyl phenyl sulfone to vinyl sulfones

Highly efficient, electrocatalytic additions of allyl phenyl sulfone to a variety of vinyl sulfones have been accomplished. The additions are catalyzed by electrogenerated bases derived from the reactant itself, and furnish 90-94% yields of highly polar molecules in which 1 mol of allyl phenyl sulfone has added consecutively, selectively, and in a linear addition mode to 2 mol of the vinyl sulfone. Essentially no products are observed which incorporate other than 2 mol of the vinyl sulfone. An addition to a difunctional alkene, divinylsulfone, yields a novel cyclization product, albeit in more moderate yield (41%). The use of tetraalkylammonium salts, as opposed to lithium salts, as electrolytes has been found to provide electrogenerated bases of especially high reactivity.     

Heteropolyacid-catalyzed direct deoxygenation of propargyl and allyl alcohols

The combination of H(3)[PW(12)O(40)]·nH(2)O (1 mol %) and Et(3)SiH led to the direct catalytic deoxygenation of propargyl alcohols, in which proper solvent selection Cl(CH(2))(2)Cl vs CF(3)CH(2)OH was the key to obtaining better product yields. Under similar conditions, the deoxygenation of allyl alcohols proceeded to give thermodynamically stable alkenes with migration of the double bonds in good yields.     

One-pot conversion of allyl alcohols into selenochroman derivatives

A one-pot conversion of allyl alcohols into selenochroman derivatives was achieved by treatment with a phenyl trimethylsilyl selenide (TMSSePh)-AIBr3 reagent system.     

Asymmetric epoxidation via phase-transfer catalysis: direct conversion of allylic alcohols into alpha,beta-epoxyketones

Studies into the use of a chiral phase-transfer catalyst in conjunction with sodium hypochlorite to effect the enantio-selective formation of alpha,beta-epoxyketones from allylic alcohols are described.     

Stereo- and regioselective routes to allylic silanes

The Ni- or Pd-catalyzed reaction of alkenyl iodides with Me₃SiCH₂Mgcl provides various types of allytrimethylsilanes in excellent yields in a highly stereo- and regioselective manner, while the Zr-catalyzed carboalumination of Me₃SiCH₂CCH followed by replacement of Al with carbon groups by known reactions produces allylsilanes represented by $\text{2}$.     

Pd-catalyzed nucleophilic allylic alkylation of aliphatic aldehydes by the use of allyl alcohols

Under catalysis of Pd(OAc)₂-(P-n-Bu)₃, Et₂Zn promotes a variety of allyl alcohols to undergo nucleophilic allylation of aliphatic aldehydes and ketones at room temperature and provides homoallyl alcohols in 60-90 and ca. 60% isolated yield, respectively. The reaction is irreversible and kinetically controlled, and unique regio- and stereoselectivities observed for the allylation with unsymmetrically substituted allyl alcohols are discussed.     

Palladium-catalyzed regio- and enantio-selective allylic substitution reaction of monosubstituted allyl substrates with benzyl alcohols

Regio- and enantio-selectivities in Pd-catalyzed allylic substitution reaction of monosubstituted allylic substrates with substituted benzyl alcohols were realized, affording the corresponding products in high regioselectivity (up to 93/7) and enantioselectivity (up to 96%).     

Highly selective palladium catalyzed kinetic resolution and enantioselective substitution of racemic allylic carbonates with sulfur nucleophiles: asymmetric synthesis of allylic sulfides,allylic sulfones,and allylic alcohols

We describe the highly selective palladium catalyzed kinetic resolutions of the racemic cyclic allylic carbonates rac-1 a-c and racemic acyclic allylic carbonates rac-3 aa and rac-3 ba through reaction with tert-butylsulfinate, tolylsulfinate, phenylsulfinate anions and 2-pyrimidinethiol by using N,N'-(1R,2R)-1,2-cyclohexanediylbis[2-(diphenylphosphino)-benzamide] (BPA) as ligand. Selectivities are expressed in yields and ee values of recovered substrate and product and in selectivity factors S. The reaction of the cyclohexenyl carbonate 1 a (>/=99 % ee) with 2-pyrimidinethiol in the presence of BPA was shown to exhibit, under the conditions used, an overall pseudo-zero order kinetics in regard to the allylic substrate. Also described are the highly selective palladium catalyzed asymmetric syntheses of the cyclic and acyclic allylic tert-butylsulfones 2 aa, 2 b, 2 c, 2 d and 4 a-c, respectively, and of the cyclic and acyclic allylic 2-pyrimidyl-, 2-pyridyl-, and 4-chlorophenylsulfides 5 aa, 5 b, 5 ab, 6 aa-ac, 6 ba and 6 bb, respectively, from the corresponding racemic carbonates and sulfinate anions and thiols, respectively, in the presence of BPA. Synthesis of the E-configured allylic sulfides 6 aa, 6 ab, 6 ac and 6 bb was accompanied by the formation of minor amounts of the corresponding Z isomers. The analogous synthesis of allylic tert-butylsulfides from allylic carbonates and tert-butylthiol by using BPA could not be achieved. Reaction of the cyclopentenyl esters rac-1 da and rac-1 db with 2-pyrimidinethiol gave the allylic sulfide 5 c having only a low ee value. Similar results were obtained in the case of the reaction of the cyclohexenyl carbonate rac-1 a and of the acyclic carbonates rac-3 aa and rac-3 ba with 2-pyridinethiol and lead to the formation of the sulfides 5 ab, 6 ab, and 6 bb, respectively. The low ee values may be ascribed to the operating of a "memory effect", that is, both enantiomers of the substrate give the substitution product with different enantioselectivities. However, in the reaction of the racemic carbonate rac-1 a as well as of the highly enriched enantiomers 1 a (>/=99 % ee) and ent-1 a (>/=99 % ee) with 2-pyrimidinethiol the ee values of the substrates and the substitution product remained constant until complete conversion. Similar results were obtained in the reaction of the cyclic carbonates rac-1 a, ent-1 a (>/=99 % ee) and ent-1 c (>/=99 % ee) with lithium tert-butylsulfinate. Thus, in the case of rac-1 a and 2-pyrimidinthiol and tert-butylsulfinate anion as nucleophiles the enantioselectivity of the substitution step is, under the conditions used, independent of the chirality of the substrate; this shows that no "memory effect" is operating in this case. Hydrolysis of the carbonates ent-1 a-c, ent-3 aa and ent-3 ba, which were obtained through kinetic resolution, afforded the enantiomerically highly enriched cyclic allylic alcohols 9 a-c (>/=99 % ee) and acyclic allylic alcohols 10 a (>/=99 % ee) and 10 b (99 % ee), respectively.     

Fast and highly regioselective allylation of indole and pyrrole compounds by allyl alcohols using Ru-sulfonate catalysts

New Ru-sulfonate catalysts have been synthesized and shown to very rapidly allylate indole and pyrrole compounds using allyl alcohols as substrates. The observed regioselectivity is exceptionally high (up to 100% of the branched isomer). Density functional theory calculations explain these results.     

Density functional theory studies on the mechanisms of regioselective allylic and cis-vinylic deprotonation of allyl amides and allylamines

A density functional theory (B3LYP/6-31+G) study was undertaken in an effort to learn more about the mechanisms controlling the regioselective deprotonations of the synthetically versatile N-lithio-N-(tert-butyl)allylamide 1 and N-lithio-N-(trimethylsilyl)allylamine 2 compounds. The calculations suggest that deprotonation of 1 occurs exclusively at the allylic position. This agrees with experimental results. The calculations also suggest that deprotonation of allylamine 2 exclusively at the cis-vinylic position is due to kinetic control.     

3,5-bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination

3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 degrees C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anti-beta-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step.     

Enantio- and regioselective iridium-catalyzed allylic hydroxylation

The first enantioselective allylic hydroxylation to prepare branched allylic alcohols directly is described. Bicarbonate was used as nucleophile in conjunction with new single component Ir-catalysts, which are stable to air and water. Excellent regio- and enantioselectivities have been achieved with a representative set of substrates.