Chiral Tertiary Alcohols Research Articles

Addressing Challenges in the Stereospecific Lithiation-Borylation of Carbamates

The enantioselective synthesis of chiral tertiary alcohols remains a challenge in organic synthesis. The authors have previously developed an approach based on the lithiation of chiral secondary carbamates and their subsequent reaction with organoboron reagents (V. K. Aggarwal and co-workers Nature 2008, 456, 778). In the present report the authors address factors which are important to the enantio­selectivity of the process and provide solutions to overcome the poor selectivity observed with challenging substrates.

Formation of chiral tertiary homoallylic alcohols via Evans aldol reaction or enzymatic resolution and their influence on the Sharpless asymmetric dihydroxylation

Enantioenriched tertiary homoallylic alcohol derivatives ( S)- 2c and ( S)- 2a were obtained via Evans aldol methodology and enzymatic resolution of racemic tertiary acetate 2e, respectively. In order to study asymmetric 1,3-induction of the stereogenic center present in 2, congener ( R)- 2a as well as its O-protected derivatives ( R)- 2b– d were submitted to Sharpless asymmetric dihydroxylation to yield the diastereomeric 1,2,4-triol derivatives (2 R,4 R)- and (2 S,4 R)- 3a– d, revealing that neither the substrate nor the Sharpless catalyst exert any stereocontrol. Similar observations were made for the less bulky alkynyl-substituted derivative 12b. However, by using a directed dihydroxylation, the anti product (2 R,4 R)- 3a was favored.

Enantioselective alkynylation of ketones with trimethoxysilylalkynes using lithium binaphtholate as a catalyst

Abstract Chiral lithium 3,3′-diphenylbinaphtholate successfully catalyzed the alkynylation of ketone with trimethoxysilylalkyne, affording chiral tertiary propargylic alcohols in high chemical yields and high enantioselectivities. The present reaction could be extended to the alkynylation of acetylpyridine, which afforded a biologically active pyridyl propargylic alcohol in good enantioselectivity.

Synthesis of chiral tertiary trifluoromethyl alcohols by asymmetric nitroaldol reaction with a Cu(ii)-bisoxazolidine catalyst

A highly enantioselective and diastereoselective copper(II)-bisoxazolidine catalyzed nitroaldol reaction with aliphatic and aromatic trifluoromethyl ketones is described.

A Spirocyclic Chiral Borate for Catalytic Enantioselective Nozaki‐Hiyama Allylation of Ketones

AbstractA new class of chiral spirocyclic borate ligands 5a–d with a rigid borocycle has been developed. The catalyst formed from chromium(II)‐5a promotes the highly efficient enantioselective Nozaki–Hiyama allylation of alkyl and aryl ketones using allyl bromide. The scope of the present method is shown to be wide, and it affords an efficient access to chiral tertiary homoallylic alcohols.

Recent Advance in Asymmetric Alkynylation of Ketones

Asymmetric alkynylation of ketones can provide versatile chiral tertiary propargylic alcohols. A series of strategies have been achieved in the past few years. Relative optimal reaction conditions for obtaining the highest enantioselectivities and yields, as well as the practical scope of different types of catalytic systems are reviewed.

Enantioselective Aldol Reaction of Tetrasubstituted Ketene Silyl Acetals with Achiral Aldehydes for the Construction of Asymmetric Tertiary Alcohols: An Application for the Divergent Total Syntheses of Buergerinins F and G

The asymmetric aldol reaction of heteroatom-substituted ketene silyl acetals with achiral aldehydes has been developed by the promotion of tin(II) triflate coordinated with a chiral diamine to afford the corresponding aldols having chiral tertiary alcohols at the α-positions. This reaction has been successfully applied to the construction of the basic skeletons of buergerinins F and G starting from achiral materials. (+)-Buergerinin G, a potentially antiphlogistic and febrifuge agent having a unique trioxatricyclo[5.3.1.0 1,5 ]undecane skeleton, is stereoselectively prepared by means of the enantioselective aldol reactions via ten linear steps from crotonaldehyde in 18% overall yield including an effective intramolecular Wacker-type ketalization of the dihydroxy-γ-lactone as a key step. In addition to the former establishment for the synthesis of (+)-buergerinin F, effective divergent methods for the preparation of buergerinins F and G were developed through a unified optically active aldol-type intermediate, which was generated from the tetrasubstituted ketene silyl acetal with crotonaldehyde by the asymmetric Mukaiyama aldol reaction.

Direct Asymmetric Catalytic Thienylaluminum Addition to Ketones: A Concise Approach to the Synthesis of (S)-Tiemonium Iodide

A direct asymmetric addition of a (2-thienyl)aluminum reagent to ketones catalyzed by a titanium catalyst of (S)-BINOL to afford chiral tertiary 2-thienyl alcohols is reported. The catalytic system works excellently for aromatic ketones and for 1-acetylcyclohexene, furnishing products in excellent enantioselectivities of up to 97% ee. However, the additions to dialkyl ketones afford products in low enantioselectivities of 8-17% ee. Importantly, a concise 3-step synthesis of (S)-tiemonium iodide with an 84% yield is demonstrated.

From allylic alcohols to chiral tertiary homoallylic alcohol: palladium-catalyzed asymmetric allylation of isatins

A palladium-catalyzed asymmetric allylation of isatins with allylic alcohols as an allyl donor was developed by using chiral spiro phosphoramidite ligands. A variety of chiral tertiary homoallylic alcohols 3-allyl-3-hydroxy-2-oxindoles were prepared directly from allylic alcohols in one step with excellent yields and moderate enantioselectivities. This represents the first catalytic asymmetric allylation of ketones with allylic alcohol as the allylating agent.

L-Proline-derived tertiary amino alcohol as a new chiral ligand for enantioselective alkynylation of aldehydes

The easily prepared chiral tertiary amino alcohol 1a was found to catalyze the reaction of alkynylzinc reagents with various aldehydes to generate chiral propargylic alcohols with moderate-to-good enantioselectivities. The mechanism of the reaction is also discussed in this Letter. A novel theoretical computation of those evaluated ligands was introduced which may supply valuable experience to help designing new chiral ligands.

Rearrangement rules

Both enantiomers of chiral tertiary alcohols can be made in a highly selective fashion from a single enantiomer of a secondary alcohol

Asymmetric total synthesis of (+)-curcutetraol and (+)-sydonol

The asymmetric total syntheses of (+)-curcutetraol and (+)-sydonol, phenolic bisabolane-type sesquiterpenoids having chiral tertiary alcohol moiety in the o-position of a phenol, were achieved in high enantiomeric excesses (99% ee). The chiral tertiary benzylic alcohol moiety of these compounds was constructed by an asymmetric synthesis using an easily available chiral aminal, (−)-(2 R,5 S)-2-methoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane. The absolute configurations of both (+)-curcutetraol and (+)-sydonol have been assumed to be S-configuration based on the stereochemical course of the well established asymmetric synthesis used in the syntheses.

Enantioselective Addition of 2-Furylaluminum to Ketones

The development of a new asymmetric 2-furyl addition of (2-furyl)aluminum to ketones is reported. The corresponding chiral tertiary furyl alcohols are versatile intermediates in organic synthesis and they are obtained in good to excellent yields.

ChemInform Abstract: Asymmetric Organocatalytic Nitroaldol Reaction of α‐Ketoesters: Stereoselective Construction of Chiral Tertiary Alcohols at Subzero Temperature.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Stereoselective Synthesis of Chiral Tertiary Alcohol Building Blocks via Neighboring Group Participation from Tri‐Substituted Olefins.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric Direct Aldol Reaction of Functionalized Ketones Catalyzed by Amine Organocatalysts Based on Bispidine

Organocatalysts containing primary-secondary amine based on bispidine and amino acid have been designed to catalyze the asymmetric direct aldol reaction of functionalized ketones including alpha-keto phosphonates, alpha-keto esters, as well as alpha,alpha-dialkoxy ketones as aldol reaction acceptors. The corresponding products with chiral tertiary alcohols were obtained in moderate to high yields (up to 97%) and high enantioselectivities (up to 98% ee). A theoretical study of transition structures demonstrated that protonated piperidine was important for the reactivity and enantioselectivity of this reaction.

Toward the continuous-flow synthesis of chiral tertiary alcohols by enantioselective addition of organozinc reagents to ketones using nanosize isoborneol ligands

The catalytic enantioselective addition of different organozinc reagents, such as alkyl or in situ generated phenylzinc derivatives to simple aryl ketones, was accomplished using titanium tetraisopropoxide and chiral ligands derived from trans-1-arenesulfonylamino-2-isoborneolsulfonylamidocyclohexane and Fréchet-type dendrons with up to 2.5 nm of diameter, giving the corresponding tertiary alcohols with enantioselectivities up to >99%. A simple and efficient procedure for the synthesis of the ligands used is also described, involving the radical addition of the corresponding thiol dendron to the chiral styryl-isoborneol derivative.

First asymmetric total synthesis of (+)-curcutetraol

The first asymmetric total synthesis of (+)-curcutetraol, a marine phenolic bisabolane-type sesquiterpene, was achieved in eight steps in ca. 50% overall yield. The chiral tertiary benzylic alcohol moiety in the o-position of a phenol was constructed in high optical yield (99% ee) by an asymmetric synthesis using a chiral aminal, (2 R,5 S)-2-methoxycarbonyl-3-phenyl-1,3-diazabicyclo[3.3.0]octane.

Asymmetric organocatalytic nitroaldol reaction of α-ketoesters: stereoselective construction of chiral tertiary alcohols at subzero temperature

Asymmetric nitroaldol reaction of α-ketoesters was explored using a guanidine–thiourea bifunctional organocatalyst at temperatures below the freezing point of water. The new reaction protocol can be applied to the nitroaldol reaction of nitroalkanes and α-ketoesters to construct the adjacent stereocenters of the chiral tertiary alcohol product with high diastereo- and enantioselectivity.

Catalytic enantioselective Reformatsky reaction with ketones

Chiral tertiary alcohols were obtained with good yields and enantioselectivities via a catalytic Reformatsky reaction with ketones, including the challenging diaryl ketones, using chiral BINOL derivatives.