Diastereoselective Addition Research Articles

Total synthesis of thioamycolamide A using diastereoselective sulfa-Michael addition as the key step

The total synthesis of the antitumor natural product thioamycolamide A has been accomplished in 19.1% overall yield featuring a diastereoselective sulfa-Michael reaction.

Rh-Catalyzed diastereoselective addition of arylboronic acids to α-keto N-tert-butanesulfinyl aldimines: synthesis of α-amino ketones

Herein we present a diastereoselective addition of arylboronic acids to α-keto N-tert-butanesulfinyl aldimines catalyzed by a Rh(i) catalyst.

Diastereoselective addition of redox active esters to azomethine imines by electrosynthesis.

Thanks to metal- and catalyst-free electrochemical conditions in an undivided cell, a series of readily available redox-active N-(acyloxy)phthalimide esters led to an efficient and highly stereoselective addition (85 : 15 to 95 : 5 dr) of putative radical species to chiral (racemic and enantioenriched) C5-substituted azomethine imines to provide an array of 31 polyaminated hydrazine derivatives as a single diastereoisomer.

Diastereoselective additions of H-phosphinates to alkenyl ketones under phase-transfer conditions.

Additions of bulky H-phosphinates to β,β-disubstituted alkenyl ketones under the action of a phase transfer-catalyst led to a new class of carbon quaternary center-containing phosphinates with unprecedented control of the relative configuration of the adjacent carbon and phosphorous chiral centers with high diastereoselectivity in most cases.

Four-Step Total Synthesis of (+)-Euphococcinine and (±)-Adaline.

A four-step enantiospecific total synthesis of bicyclic homotropinone alkaloid euphococcinine and a racemic synthesis of adaline were reported. Key reactions in the synthesis are the diastereoselective addition of a Wittig phosphorene to the ketimines derived from Davis-Ellman sulfinamides, ring-closing metathesis, and intramolecular Michael reactions.

Diastereoselective Synthesis of Morpholine Derivatives from Grignard Reagents and N-Sulfinyl Imines

AbstractThe stereoselective synthesis of substituted morpholine derivatives has been achieved through a two-step process involving diastereoselective addition of a Grignard reagent to a sulfinyl imine, followed by cyclization.

Cobalt-Catalyzed C-H Activation and [3 + 2] Annulation with Allenes: Diastereoselective Synthesis of Indane Derivatives.

An unprecedented bidentate directing-group-assisted cobalt-catalyzed oxidative C-H activation of aryl hydrazones followed by a syn-diastereoselective [3 + 2] annulation reaction has been achieved, employing allenes as the annulation partners. The selective 2,3-migratory insertion of allenes with arylcobalt(III) species and the subsequent intramolecular diastereoselective nucleophilic addition of η1-allylcobalt onto the imine resulted in [3 + 2] annulation over the alternative [4 + 2] annulation. Furthermore, the oxidative annulation obviates the need for stoichiometric metal oxidants and proceeds under aerobic conditions.

The Catalytic Regio- and Stereoselective Synthesis of 1,6-Diazabicyclo[4.3.0]nonane-2,7-diones.

A straightforward synthesis of original 1,6-diazabicyclo[4.3.0]nonane-2,7-diones was achieved through a DBU-organocatalyzed multicomponent Knoevenagel-aza-Michael-Cyclocondensation reaction which takes advantage of an unprecedented highly regio- and diastereoselective conjugate addition of pyridazinones to alkylidene Meldrum's acid intermediates. The key reactive intermediates of this complex process were analyzed by means of electrospray ionization mass spectrometry coupled to ion mobility spectrometry, allowing us to validate the proposed mechanism.

Diastereoselective photochemical radical addition of a cyclic ether to olefins: addition of THF radicals to dialkyl maleates

Diastereoselective photochemical radical addition of a cyclic ether to olefins: addition of THF radicals to dialkyl maleates

Synthesis of the C1−C16 Polyol‐Containing Macrolactone of 13‐Desmethyl Lyngbouilloside, an Unnatural Analog of the Originally Assigned Structure of (−)‐Lyngbouilloside

AbstractThe synthesis of the C1−C16 polyol‐containing macrolactone of 13‐desmethyl lyngbouilloside, an unnatural analog of the originally assigned structure of (−)‐lyngbouilloside is reported. Synthesis of the C1−C16 acyclic backbone is achieved via iterative use of a phosphate tether‐mediated one‐pot sequential, RCM/CM/chemoselective diimide reduction, with concomitant use of a regio‐ and diastereoselective cuprate addition using Me2Zn/CuCN ⋅ 2LiCl or Pd‐catalyzed reductive allylic transposition, respectively on bicyclo[4.3.1]phosphate‐containing subunits. Subsequent oxidative cleavage and Roskamp homologation completes the pathway to the C1−C16 acyclic fragment. Two routes to the macrocyclic core were explored with mixed success, (i) a Boeckman‐type acylketene trapping of the C13 secondary carbinol and (ii) an alternative route employing acid‐catalyzed pyran‐mixed ketal formation via reaction of the C7 secondary carbinol with the β‐keto ester using trimethylorthoformate, and subsequent Yamaguchi cyclization.

An intramolecular oxa-Michael addition on prebuilt β-lactam tethered α, β-unsaturated ester: A remarkable synthesis of a unique scaffold of 2,3-fused β-lactam-1,4-dioxepane

An expeditious base assisted highly diastereoselective intramolecular oxy-Michael addition reaction in the synthesis of enantiomerically pure 1,4-dioxepane fused β-lactam has been described. This present study has been portrayed a rapid intramolecular 7-exo-trig oxy-Michael reaction involving chemoselective nucleophilic addition of 20 alcohol of the vic-diols to an α β-unsaturated ester. Furthermore, the developed methodology elaborates an extremely atom-economical approach in constructing the C–O bond in stereoselective fashion under mild reaction conditions.

Diastereoselective Copper-Mediated Conjugate Addition of Functionalized Magnesiates for the Preparation of Bisaryl Nrf2 Activators.

A two-step metal-halogen exchange and diastereoselective copper-mediated Michael addition onto a complex α,β-unsaturated system has been developed and applied toward the synthesis of bisaryl Nrf2 activators. Optimization of metal-halogen exchange using (n-Bu)3MgLi allowed for the preparation of custom aryl-functionalized magnesiate reagents at noncryogenic temperatures. Following transmetalation, these reagents were used in highly diastereoselective Michael addition reactions.

Photoredox Asymmetric Nucleophilic Dearomatization of Indoles with Neutral Radicals

The dearomatization of indoles represents the most efficient approach for accessing highly valued indolines. The inherent nucleophilic reactivity of indoles has dictated indole dearomatization development in both 1e– and 2e– processes. However, the dearomatization of electron-deficient indoles has been challenging. Herein, we introduce a conceptually distinct photoredox-mediated Giese-type transformation strategy, which is generally used for the conjugate addition of radicals to simple α, β-unsaturated systems, for chemoselectively breaking C═C bonds embedded in the aromatic structure. Moreover, highly diastereoselective addition of challenging neutral radicals has been achieved by Oppolzer camphorsultam chiral auxiliary. Structurally diverse amine-functionalized chiral indolines carrying distinct functional and stereochemical diversity are produced from a wide array of amines as radical precursors. Furthermore, the mild, powerful manifold is capable of the late-stage modification of complex natural products and pharmaceuticals. DFT studies are performed to elucidate the observed stereochemical outcomes.

Synthesis of Proline Analogues via Rh-Catalyzed Asymmetric Conjugate Addition

An enantio- and diastereoselective Rh-catalyzed conjugate addition reaction for the synthesis of proline analogues is reported. A high-throughput experimentation campaign was used to identify an ef...

Copper-Catalyzed Regio- and Diastereoselective Additions of Boron-Stabilized Carbanions to Heteroarenium Salts: Synthesis of Azaheterocycles Containing Contiguous Stereocenters

Nucleophilic addition of diborylalkyl reagents to N-alkyl or N-acylpyridinium and related heteroarenium salts has been developed as a key step for the synthesis of nonaromatic nitrogen heterocycles that contain contiguous stereogenic centers. Derivatization of the dihydropyridine products for the synthesis of tetrahydropyridines and piperidines have also been described.

Diastereodivergent Synthesis of 2-Ene-1,4-hydroxy Sulfides from 2-Sulfinyl Dienes via Tandem Sulfa-Michael/Sulfoxide-Sulfenate Rearrangement

The highly diastereoselective sulfa-Michael addition of thiolates to enantiopure 2-sulfinyl dienes leads to anti or syn 2-ene-1,4-hydroxy sulfides in good yields and selectivities dependent on the reaction conditions in a diastereodivergent process. Synthetic applications of these enantiopure hydroxy sulfides by subsequent sigmatropic rearrangements have been outlined.

Asymmetric Total Synthesis and Assignment of Absolute Configuration of Arbornamine.

The asymmetric total synthesis of arbornamine was accomplished in 13 steps, leading to the assignment of its absolute configuration. The key features of the strategy include construction of the C16 quaternary carbon center by a highly diastereoselective Grignard reagent addition to N-tert-butanesulfinylimine, sequential site-selective amidation and N-alkylation to form the C and E rings, and [Ni(COD)2]-mediated Michael addition to close the D ring.

General Synthesis of Cyclopropanols via Organometallic Addition to 1-Sulfonylcyclopropanols as Cyclopropanone Precursors.

The addition of organometallic reagents to ketones constitutes one of the most straightforward synthetic approaches to tertiary alcohols. However, due to the absence of a well-behaved class of cyclopropanone surrogates accessible in enantioenriched form, such a trivial synthetic disconnection has received very little attention in the literature for the formation of tertiary cyclopropanols. In this work, we report a simple and high-yielding synthesis of 1-substituted cyclopropanols via the addition of diverse organometallic reagents to 1-phenylsulfonylcyclopropanols, acting here as in situ precursors of the corresponding cyclopropanones. The transformation is shown to be amenable to sp-, sp2-, or sp3-hybridized organometallic C-nucleophiles under mild conditions, and the use of enantioenriched substrates led to highly diastereoselective additions and the formation of optically active cyclopropanols.

Highly stereoselective synthesis of non-racemic 3-substituted dihydro-benzo[de]isoquinolinones via an addition-cyclization-substitution method

Substituted dihydrobenzo[de]isoquinolinones were synthesized via diastereoselective addition of Grignard reagents to the N-tert-butylsulfinylimine derived from 1,8-naphthaldehydic methyl ester, followed by cyclization and substitution at the sulfur atom. The products were obtained in 25–98% yield and with enantiomeric excess of 46–99%.

Synthesis of Quaternary Carbon Stereogenic Centers by Diastereoselective Conjugate Addition of Boron-Stabilized Allylic Nucleophiles to Enones.

A method for the site-selective and diastereoselective conjugate addition of boron-stabilized allylic nucleophiles to α,β-unsaturated ketones is disclosed. Transformations involve easily prepared γ,γ-disubstituted allyldiboron reagents and proceed in the presence of a fluoride activator at 80 °C. Reactions proceed with a wide variety of enones and allyldiboron reagents efficiently to deliver ketone products that contain otherwise difficult-to-access vicinal β-tertiary and γ-quaternary carbon stereogenic centers and an alkenylboron moiety. The utility of the method is highlighted by several transformations, including cross-coupling and carbocyclizations.