Racemic Allylic Alcohols Research Articles

Dynamic Kinetic Resolution of Racemic Allylic Alcohols via Hydrolase–Metal Combo Catalysis: An Effective Method for the Synthesis of Optically Active Compounds

Abstract This review focuses on the dynamic kinetic resolution (DKR) of racemic allylic alcohols to produce allylic esters in high chemical and optical yields, which was achieved by combining hydrolase-catalyzed kinetic resolution and in situ racemization of the remaining less reactive enantiomers. Two classes of racemization catalysts, e.g., Ru complexes and oxovanadium compounds, are mainly discussed. Typical examples of DKR are shown along with their application in the concise syntheses of optically active compounds as valuable synthetic intermediates. The domino process integrating DKR with the active use of the installed acyl moiety for subsequent intramolecular cyclization is also discussed, which has great potential for the asymmetric syntheses of optically active fused cyclic molecules possessing multiple stereogenic centers.

Stereodivergent α-Allylation of Linear Aldehydes with Dual Iridium and Amine Catalysis

We describe the fully stereodivergent, dual catalytic α-allylation of linear aldehydes. The reaction proceeds via direct iridium-catalyzed substitution of racemic allylic alcohols with enamines generated in situ. The use of an Ir(P,olefin) complex and a diarylsilyl prolinol ether as catalysts in the presence of dimethylhydrogen phosphate as the promoter proved to be crucial for achieving high enantio- and diastereoselectivity (>99% ee, up to >20:1 dr). The utility of the method is demonstrated in a concise enantioselective synthesis of the antidepressant (-)-paroxetine.

Iridium-Catalyzed Enantioselective Allyl–Alkene Coupling

The direct Ir-catalyzed cross-coupling between branched, racemic allylic alcohols and simple olefins is described. This transformation is catalyzed by an Ir-(P,olefin) complex and proceeds with high site selectivity and excellent enantioselectivity. The method allows rapid access to various 1,5-dienes or trienes and was used in the catalytic asymmetric synthesis of the γ-secretase modulator JNJ-40418677.

ChemInform Abstract: Iridium‐Catalyzed Enantioselective Allylic Alkynylation.

AbstractThis method allows the highly enantioselective substitution of racemic allylic alcohols with potassium alkynyltrifluoroborates with excellent branched‐to‐linear selectivity.

ChemInform Abstract: Iridium‐Catalyzed Enantioselective Polyene Cyclization.

AbstractA new enantioselective polyene cyclization reaction from unactivated branched racemic allylic alcohols in the presence of an iridium catalyst is described.

ChemInform Abstract: Enantioselective Allylic Thioetherification: The Effect of Phosphoric Acid Diester on Iridium‐Catalyzed Enantioconvergent Transformations.

AbstractThe effect of phosphate as a catalyst in combination with its properties as a leaving group is exploited in an enantioconvergent thioetherification of racemic allylic alcohols.

Iridium-Catalyzed Enantioselective Allylic Vinylation

The first example of Ir-catalyzed asymmetric substitution reaction with vinyl trifluoroborates is described. The direct reaction between branched, racemic allylic alcohols and potassium alkenyltrifluoroborates proceeded with high site selectivity and excellent enantioselectivity (up to 99%) mediated by an Ir-(P,olefin) complex. This method allows rapid access to various 1,4-dienes or trienes including the biologically active natural products (-)-nyasol and (-)-hinokiresinol.

Iridium-Catalyzed Enantioselective Polyene Cyclization

A highly enantioselective polycyclization method has been developed using the combination of Lewis acid activation with iridium-catalyzed allylic substitution. This strategy relies on direct use of branched, racemic allylic alcohols and furnishes a diverse and unique set of carbo- and heteropolycyclic ring systems in good yields and ≥99% ee.

Enantioselective Allylic Thioetherification: The Effect of Phosphoric Acid Diester on Iridium‐Catalyzed Enantioconvergent Transformations

You'll take the high road and I'll take the low road: Enantioenriched allylic thioethers have been synthesized from chiral racemic allylic alcohols. The combination of an Ir-(P,alkene) complex and dibutyl phosphoric acid are required to attain high selectivities. Mechanistic studies uncover an enantioconvergent transformation in which substrate enantiomers react along different pathways to give the same product (see scheme; cod=1,5-cyclooctadiene).

Synthetic studies toward potent cytostatic macrolide bryostatin: an expedient synthesis of C1–C10 fragment

The stereoselective synthesis of C1–C10 fragment of cytostatic macrolide bryostatin is described. Two of the three chiral centers have been established via the Sharpless kinetic resolution of racemic allylic alcohol 15 followed by regioselective reduction of epoxy alcohol 8 with Red-Al. Diastereoselective Aldol reaction of an aldehyde 7 with methyl isobutyrate affords the corresponding β-hydroxyester 23 which is then transformed into tetrahydropyran ring system 3 via an intramolecular hemi-ketalization.

ChemInform Abstract: Development of Environmentally Benign Transformations via 1,3‐Transposition of Hydroxyl Group

AbstractReview: 24 refs.

Development of Environmentally Benign Transformations <i>via</i> 1,3-Transposition of Hydroxyl Group

This review article describes our recent efforts to develop environmentally benign transformations of allyl and propargyl alcohols via the 1,3-transposition of their hydroxyl groups using combined catalyst systems. This methodology allows for successful transformation under mild conditions, which has never been achieved using each catalyst. Representative examples of this methodology include the following three reactions. First, the combination of oxo-vanadium compounds and lipases resulted in the dynamic kinetic resolution of racemic allyl alcohols to give optically active allyl esters in high yields. Second, Mo-Au-Ag combination catalysis dramatically accelerated the rearrangement of diverse propargyl alcohols into α,β-unsaturated carbonyl compounds. Finally, the choice of suitable heteropoly acids for the rearrangement of propargyl alcohols led to the selective preparation of both (Z)- and (E)-enones.

Kinetic resolution of allylic alcohols via stereoselective acylation catalyzed by lipase PS-30

By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic allylic alcohols has been achieved via stereoselective acylation. The value of kinetic enantiomeric ratio ( E) reached up to 968. Substituent effect is briefly discussed.

Ruthenium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution with Water: Direct Synthesis of Chiral Allylic Alcohols

Enantioselective allylic substitution catalyzed by transitionmetal complexes is an important process in organic synthesis. For many years, mainly palladium complexes that contain chiral ligands have been employed as efficient catalysts in these reactions. Recent studies have demonstrated that chiral catalysts based on other transition metals show different regioselectivity in the synthesis of branched allylic products via monosubstituted p-allyl intermediates. Although a variety of carbon and nitrogen nucleophiles can be used in those reactions, applicable oxygen nucleophiles are still limited to phenols and alcohols, which produce allylic ethers. Thus, enantioenriched branched allylic alcohols, which serve as useful chiral building blocks, are often synthesized by other processes, such as the hydrogenation of a,b-unsaturated ketones, the nucleophilic addition of vinylmetal reagents to aldehydes and ketones, and the kinetic resolution of racemic allylic alcohols. Recently, new ways to access these compounds have been developed, and they involve allylic substitution by a two-step conversion involving allylic esters and silyl ethers (Scheme 1; OPG= ester or silyl

Asymmetric synthesis of highly functionalized cyclopentanes by a rhodium- and scandium-catalyzed five-step domino sequence

A domino sequence has been developed between vinyldiazoacetates and racemic allyl alcohols, involving five distinct steps. The sequence generates highly functionalized cyclopentanes with four new stereogenic centers as single diastereomers in 64-92% ee. The first step is a rhodium-catalyzed oxygen ylide formation, which is then followed by a [2,3]-sigmatropic rearrangement, an oxy-Cope rearrangement, a keto/enol tautomerization, and then finally a carbonyl ene reaction. With appropriate substrates, a further silyl deprotection and a 6-exo-trig cyclization can be added to the domino process.

One-Pot Synthesis of Optically Active Allyl Esters via Lipase−Vanadium Combo Catalysis

The combination of vanadium-oxo compounds (3 or 4) with a lipase produced the regio- and enantioconvergent transformation of racemic allyl alcohols (1 or 2) into optically active allyl esters. In this system, the vanadium compounds catalyzed the continuous racemization of the alcohols along with the transposition of the hydroxyl group, while the lipase effected the chemo- and enantioselective esterification to achieve the dynamic kinetic resolution.

ChemInform Abstract: Chemical Resolution of Allylic Alcohols.

Abstract Asymmetric epoxydation of a racemic allylic alcohol followed by acetylation, chromatography, and deoxygenation (WCl6, n-BuLi) has led to the individual optically active enantiomers.

Enantioselective C−C Bond Formation by Rhodium-Catalyzed Tandem Ylide Formation/[2,3]-Sigmatropic Rearrangement between Donor/Acceptor Carbenoids and Allylic Alcohols

The rhodium-catalyzed reaction of racemic allyl alcohols with methyl phenyldiazoacetate or methyl styryldiazoacetate results in a two-step process, an initial oxonium ylide formation followed by a [2,3]-sigmatropic rearrangement. This process competes favorably with the more conventional O-H insertion chemistry as long as donor/acceptor carbenoids and highly substituted allyl alcohols are used as substrates. When the reactions are catalyzed by Rh(2)(S-DOSP)(4), tertiary alpha-hydroxycarboxylate derivatives with two adjacent quaternary centers are produced with high enantioselectivity (85-98% ee).

Tandem reactions for streamlining synthesis: enantio- and diastereoselective one-pot generation of functionalized epoxy alcohols.

[Reaction: see text] In 1980, Sharpless and Katsuki introduced the asymmetric epoxidation of prochiral allylic alcohols (the Sharpless-Katsuki asymmetric epoxidation), which enabled the rapid synthesis of highly enantioenriched epoxy alcohols. This reaction was a milestone in the development of asymmetric catalysis because it was the first highly enantioselective oxidation reaction. Furthermore, it provided access to enantioenriched allylic alcohols that are now standard starting materials in natural product synthesis. In 1981, Sharpless and co-workers made another seminal contribution by describing the kinetic resolution (KR) of racemic allylic alcohols. This work demonstrated that small-molecule catalysts could compete with enzymatic catalysts in KRs. For these pioneering works, Sharpless was awarded the 2001 Nobel Prize with Knowles and Noyori. Despite these achievements, the Sharpless KR is not an efficient method to prepare epoxy alcohols with high enantiomeric excess (ee). First, the racemic allylic alcohol must be prepared and purified. KR of the racemic allylic alcohol must be stopped at low conversion, because the ee of the product epoxy alcohol decreases as the KR progresses. Thus, better methods to prepare epoxy alcohols containing stereogenic carbinol carbons are needed. This Account summarizes our efforts to develop one-pot methods for the synthesis of various epoxy alcohols and allylic epoxy alcohols with high enantio-, diastereo-, and chemoselectivity. Our laboratory developed titanium-based catalysts for use in the synthesis of epoxy alcohols with tertiary carbinols. The catalysts are involved in the first step, which is an asymmetric alkyl or allyl addition to enones. The resulting intermediates are then subjected to a titanium-directed diastereoselective epoxidation to provide tertiary epoxy alcohols. Similarly, the synthesis of acyclic epoxy alcohols begins with asymmetric additions to enals and subsequent epoxidation. The methods described here enable the synthesis of skeletally diverse epoxy alcohols.

Enantiomerically pure allylic alcohols: preparation by Candida parapsilosis ATCC 7330 mediated deracemisation

Biocatalytic deracemisation of racemic allylic alcohols by whole cells of Candida parapsilosis ATCC 7330 resulted in the formation of the ( R)-enantiomers in high enantiomeric excesses (up to >99%) and isolated yields (up to 79%).