Kinetic resolution of allylic alcohols using a chiral phosphine catalyst

[reaction: see text] The kinetic resolution of racemic allylic alcohols 3, 6, and 12--17 has been explored using the PBO catalyst 7 for activation of isobutyric anhydride. Trisubstituted allylic alcohols (12--15; 17) are the best substrates and react with an enantioselectivity of s = 32--82 at -40 degrees C.     

Ultrasound-accelerated synthesis of chiral allylic alcohols promoted by indium metal

The 2-iodomethyl-O-isopropylidine acetals undergo smoothly β-elimination by indium metal in methanol under sonication to afford the corresponding allylic alcohols in excellent yields with high selectivity. This method tolerates both acid and base labile functional and protecting groups and also free hydroxyl groups present in the molecule. Improved yields and enhanced rates are the remarkable features obtained by ultrasound.     

A chiral electrophilic selenium reagent to promote the kinetic resolution of racemic allylic alcohols

[reaction: see text] The first example of a kinetic resolution process promoted by electrophilic selenium reagents is reported. Racemic allylic alcohols react with half equivalents of a selenenylating agent in methanol leading to the regiospecific formation of the corresponding addition products with a very high level of facial selectivity (from 95:5 to 98:2 dr). The unreacted alcohols can be recovered in an optically enriched form (from 90 to 94% ee).     

One-pot synthesis of cage alcohols

An efficient one-pot procedure has been developed for the synthesis of cage alcohols with hydroxy groups in the bridgehead positions. The procedure includes initial nitroxylation with nitric acid or a mixture of nitric acid with acetic acid and subsequent hydrolysis in the presence of urea.     

One-pot asymmetric synthesis of acyclic chiral epoxy alcohols via tandem vinylation-epoxidation with dioxygen

[reaction: see text] We have developed a one-pot procedure for the asymmetric synthesis of a synthetically challenging class of acylic secondary epoxy alcohols with three contiguous stereocenters from simple achiral starting materials. The epoxy alcohols are synthesized via a tandem catalytic asymmetric vinylation of an aldehyde coupled with a diastereoselective epoxidation reaction. A vinylzinc reagent generated in situ undergoes enantioselective addition to an aldehyde in the presence of a zinc catalyst to provide an allylic zinc alkoxide. This species is then epoxidized by addition of dioxygen and a titanium tartrate catalyst to give epoxy alcohols with excellent enantioselectivities, in most cases, and with diastereoselectivities up to 4.5:1 in favor of the threo-diastereomer. The system described herein represents a significant advance in terms of synthetic efficiency and selectivity.     

Liquid-phase synthesis of chiral tartrate ligand library for enantioselective sharpless epoxidation of allylic alcohols

This paper reports a successful development of a group of efficient soluble polymer-supported chiral tartrate ligands by liquid-phase synthesis for Sharpless epoxidation of a variety of allylic alcohols through ligand diversity. The influence of substituent in chiral tartrate ligands on the enantioselectivities of the reaction was disclosed. Moderate chemical yields and good enantiomeric excesses were obtained by using soluble polymer-supported tartrate ester in the epoxidation of allylic alcohols with Ti(O-i-Pr)(4)/tert-butyl hydroperoxide.     

Enzymatic resolution of racemic secondary cyclic allylic alcohols

The resolutions of five racemic cyclic alcohols: 6,6-dimethylcyclohex-2-en-1-ol (±)-5, 4,4-dimethylcyclohex-2-en-1-ol (±)-7, 5,5-dimethylcyclohex-2-en-1-ol (±)-11 and isomeric trans-(±)-13 and cis-piperitols (±)-14 are presented. They were resolved by enzymatic esterification with vinyl esters or by enzymatic hydrolysis of their racemic esters in phosphate buffer. The following lipases were used as biocatalysts: Novozyme 435 (Candida antarctica), Amano PS (Burkholderia cepacia) and lipase from Candida cylindracea. All isomers of alcohols were obtained with at least 96% ee.     

Diastereoselective zinco-cyclopropanation of chiral allylic alcohols with gem-dizinc carbenoids

The highly diastereoselective zinco-cyclopropanation of chiral allylic alcohols using gem-dizinc carbenoids is described. The reaction produces three contiguous stereogenic centers, and the resulting chiral cyclopropylzinc derivatives can be trapped with electrophiles with retention of configuration. Simple functional group manipulations lead to the efficient synthesis of orthogonally protected 1,2,3-substituted cyclopropane derivatives.     

Preparation of optically active allylic hydroperoxy alcohols and 1, 3-diols by enzyme-catalyzed kinetic resolution and photooxygenation of chiral homoallylic alcohols

All four possible enantiomers of the 3-hydroperoxy-4-penten-1-ols 2a, b and their corresponding 4-pentene-1,3-diols 4a,b have been prepared for the first time in high enantiomeric purity (up to 98% ee) and in preparative amounts according to two distinct ways: First the photooxygenation of the racemic homoallylic alcohols 1 gave the racemic hydroperoxy alcohols 2, which have subsequently been kinetically resolved by horseradish peroxidase (HRP); alternatively, first the lipase-catalyzed resolution afforded the optically active homoallylic alcohols 1 and subsequent photooxygenation led to the enantiomerically enriched hydroperoxy alcohols 2.     

Palladium-catalyzed asymmetric synthesis of allylic alcohols from unsymmetrical and symmetrical racemic allylic carbonates featuring C-O-bond formation and dynamic kinetic resolution

Described is the asymmetric synthesis of the allylic alcohols 11 (85% ee), 15 (99% ee), 17 (93% ee), 19 (61% ee), and 21 (69% ee) through a Pd-catalyzed reaction of the unsymmetrical carbonates rac-10, rac-12, rac-14, rac-16, rac-18, and rac-20, respectively, with KHCO₃ and H₂O in the presence of bisphosphane 6. Similarly the allylic alcohols 23 (99% ee) and 25 (97% ee) have been obtained from the symmetrical carbonates rac-22 and rac-24, respectively. Reaction of the meso-biscarbonate 26 with H₂O and Pd(0)/6 afforded alcohol 27 (96% ee), which was converted to the PG building block 32. The unsaturated bisphosphane 33 showed in the synthesis of alcohols 36, 37, and 39 a similar high selectivity as 6. The formation of alcohols 11, 15, and 17 involves an efficient dynamic kinetic resolution.     

One-pot synthesis of chiral nonracemic amines

One-pot five-component reactions of oxathiazolidine-S-oxides with mesitylmagnesium bromide, lithium bis(trimethylsilyl)amide, aldehydes and Grignard reagents afford chiral nonracemic amines or sulfinamides in good yields and high stereoselectivities.     

Stereoselectivity in the hydroboration of chiral cyclohexane-derived allylic alcohols

The isomeric 2-ethylidenecyclohexanols are hydroborated by t-hexylborane with weak stereoselectivity whilst 1-(1′-hydroxyalkyl)cyclohexenes show up to 50:1 discrimination.     

One-pot synthesis of chiral multifunctionalized aziridines

A direct synthetic procedure to obtain chiral aziridines is reported, involving a diastereoselective aza-MIRC (Michael Initiated Ring Closure) reaction. Multifunctionalized aziridines are obtained in high overall yields (82-92%) and with a diastereomeric ratio up to 99:1. Further synthetic elaboration can lead to the formation of interesting biochemical molecules, such as amino glycosides. The diastereomeric induction seems to be strongly controlled both by the choice of chiral moiety and by the electron withdrawing groups (EWG) present on the starting alkenes.     

Pd-catalyzed asymmetric synthesis of allylic tert-butyl sulfones and sulfides: Kinetic resolution of the allylic substrate by a chiral Pd-complex

The acyclic and cyclic allylic tert-butyl sulfones 3, ent-3, 11a, 11b and 15a–c of 89–98% ee were synthesized in 40–92% yield by a Pd-catalyzed reaction of the respective allylic acetates and carbonates rac-1a, rac-1b, rac-10a, rac-10b and rac-14a–c with LiO₂St-Bu in the presence of the chiral ligands 2a, ent-2b and 12. Formation of the n-butyl sulfones 13a and 13b of 95% ee was observed. Reactions of rac-1a and 1b/ent-1b with LiO₂St-Bu in the presence of 2a and ent-2b, respectively, in THF under heterogeneous conditions were accompanied by a kinetic resolution of the allylic substrates. The faster reacting allylic substrate and the preferentially formed sulfone had the same absolute configuration. The allylic tert-butyl sulfide 17 of 92% ee was obtained in 63% yield by the Pd-catalyzed reaction of rac-1b with Me₃SiSt-Bu in the presence of ent-2b.     

One-pot synthesis of chiral azetidines from chloroaldehyde and chiral amines

A variety of chiral azetidinepiperidines have been synthesized utilizing an expedient one-pot union of piperidine chloroaldehyde with chiral amines. This two step one-pot procedure provides access to an interesting set of compounds that retain the chiral purity of the starting chiral amine.     

One-pot synthesis of tetrahydrofuran derivatives from allylic alcohols and vinyl ethers by means of palladium(II) acetate

Treatment of a mixture of allylic alcohol and vinyl ether in the presence of Pd(OAc)₂ provides 2-alkoxy-4-alkenyltetrahydrofuran in good yield.     

Lipase-catalyzed kinetic resolution of aryltrimethylsilyl chiral alcohols

Lipase-catalyzed kinetic resolution of aryltrimethylsilyl chiral alcohols through a transesterification reaction was studied. The optimal conditions found for the kinetic resolution of m- and p-aryltrimethylsilyl chiral alcohols, led to excellent results, high conversions (c = 50%), high enantiomeric ratios (E > 200) and enantiomeric excesses for the remaining (S)-alcohol and (R)-acetylated product (>99%). However, kinetic resolution of o-aryltrimethylsilyl chiral alcohols did not occur under the same conditions applied to the other isomers.     

Catalytic asymmetric synthesis of chiral allylic esters

Trichloroacetimidate derivatives of prochiral (Z)-2-alken-1-ols react at room temperature with carboxylic acids to give chiral 3-acyloxy-1-alkenes in high enantiopurity in the presence of di-mu-acetatobis[(eta5-(S)-(pR)-2-(2'-(4'-methylethyl)oxazolinyl)cyclopentadienyl,1-C,3'-N)(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium (COP-OAc) or its enantiomer. This reaction has broad scope, proceeds with predictable high stereoinduction, is accomplished at room temperature using high substrate concentrations and low catalyst loadings, and likely proceeds by a novel mechanism.