Tandem Acylation and Aromatization of Vinylogous Esters: A Regiospecific Approach to Resorcinyl Ketones.

This study demonstrates the direct conversion of vinylogous esters into selectively protected 6-acyl resorcinols (4-alkoxy/aryloxy-2-hydroxy arylketones) in a regiospecific manner. Resorcinyl ketones are first-time synthesized, diverging from their traditional roots, originating from non-benzenoid pool materials. Converting cyclohexenones into phenol- or resorcinol-based arylketones remains challenging due to the stability and reactivity issues of intermediate products.

Cooperative Noncovalent Interactions Controlling Amine-Catalyzed Aldol Reaction Pathways Catalyzed by the Bifunctional Amino Quaternary Phosphonium Ion.

Members of a new class of bifunctional amino quaternary phosphonium salts have been synthesized and utilized as catalysts in aldol condensation reactions, as demonstrated herein. These secondary amines feature a phosphonium ion connected by a carbon chain, enabling the quaternary phosphonium ion to engage in distinct cooperative noncovalent interactions. These interactions work in tandem to stabilize different transition state complexes, exclusively controlling competing amine-catalyzed aldol pathways via the Mannich mechanism.

Effective Alkoxide Trapping by TMSX in the Presence of TPP Catalyst in Glycidol Acetal Rearrangements.

This study demonstrates a nucleophile-catalyzed, trimethylsilyl halide-promoted rearrangement reaction of glycidol acetals to form halogenated cyclic acetals. The acetal group has been activated selectively in the presence of trimethylsilyl cation, which is used as -generated alkoxide trapping reagent. Nucleophilic chloride and bromide ions participate in addition reactions with epoxides predominantly via S1-type epoxide opening, while non-nucleophilic iodide and triflate ions induce a positive charge at the epoxide carbon.

TMSCl Promoted Direct Conversion of Cyclic Anhydrides to (Un)Symmetric-Diesters/Amide Esters.

We present a mild, efficient, and one-pot method for the silyl-promoted transformation of cyclic anhydrides into homo- and hetero-dicarboxylic acid diesters and amide esters. This versatile reaction operates under ambient conditions, on a gram scale, and accommodates a wide range of alcohols, amines, and cyclic anhydrides. The one-pot process involves a two-step sequence, starting with the nucleophilic opening of anhydride by an amine or alcohol, followed by esterification.

Phosphonium Ion-Tethered Secondary Amines for Chemospecific 5- Aldol Condensations of 6-Ketoaldehydes.

A novel and highly selective 5--- aldol condensation of 6-ketoaldehydes is presented using a proline-based alkylphosphonium ion catalyst. Bulky and oxophilic phosphonium ion plays a vital role in facilitating kinetic aldenamine formation and activating keto groups for aldol addition. This innovative approach exclusively targets five-membered carbo- and heterocyclic aldehydes, involving unusual aldehydes as donors and ketones as acceptors.

Highly Regio- and Stereoselective Intramolecular Rearrangement of Glycidol Acetal to Alkoxy Cyclic Acetals.

A new class of highly regio- and stereoselective intramolecular rearrangements of glycidol acetals to produce alkoxylated 1,3-dioxolane/1,3-dioxane is demonstrated. Selective Lewis acid activation of acetal generates an oxocarbenium ion that initiates the epoxide ring-opening event, giving the bicyclic [3,1,0]epoxonium ion intermediate that undergoes /-selective opening by a tethered alkoxide. Mechanistic insights into preferential acetal activation over the epoxide were obtained by crossover experiments.

The influence of α-coordinating groups of aldehydes on /-selectivity and the use of quaternary ammonium counter ions for enhanced -selectivity in the Julia-Kocienski reaction.

Modified reaction conditions for improved -selectivity of olefins in the Julia-Kocienski reaction of aldehydes having α-coordinating substituents are demonstrated. The chelating groups in aldehydes are expected to stabilize the -transition state with metal ions, whereas the weakly coordinating quaternary ammonium ions are devoid of all possible chelating interactions to enhance -selectivity. A systematic investigation is presented to study the size of the neighbouring protecting groups of aldehydes and their chelation effect on /-selectivity in the Julia-Kocienski reaction.

Stereoselective Total Synthesis of (-)-(2,4)-3'-Methoxyl Citreochlorol: Preparation and Use of New Proline-Based Auxiliary for Asymmetric Acetate Aldol Reaction.

The first stereoselective total synthesis of (-)-(2,4)-3'-methoxy citreochlorol and (-)-(2,4)-3'-methoxy citreochlorol is demonstrated. A proline-based imidazolidinone was synthesized and used as chiral auxiliary for asymmetric acetate aldol reaction to generate initial chirality in the targeted molecule. Geminal dichloromethane functionality was introduced by the addition of in situ generated dichloromethyllithium to Weinreb's amide functional group.

A Method for the Preparation of β-Amino-α,β-unsaturated Carbonyl Compounds: Study of Solvent Effect and Mechanism.

An efficient method for the preparation of β-amino-α,β-unsaturated carbonyl compounds is demonstrated. Bench-stable sodium 3-oxo-enolates were prepared from carbonyl compounds, and reacted with amines in the presence of an acid and a desiccant. DFT studies revealed contrasting mechanisms toward the reactivity of aliphatic amines in protic solvents and aromatic amines in aprotic solvents.

A New, Short, and Stereocontrolled Synthesis of C-Symmetric 1,2-Diamines.

The previously unknown 5-spirocyclohexylisoimidazole has been made efficiently and simply by reaction of ammonia, glyoxal hydrate, and cyclohexanone. It is a very useful precursor for the diastereocontrolled synthesis of many C-symmetric 1,2-diamines, a class which is important for the generation of a variety of C-symmetric reagents and catalysts for enantioselective synthesis.

A systematic study of functionalized oxiranes as initiating groups for cationic polycyclization reactions.

Three different methods have been developed that effectively utilize chiral oxiranes derived from Katsuki-Sharpless epoxidation of allylic alcohols as initiating groups for cationic cyclization of unsaturated substrates to form chiral polycycles. This type of transformation has previously been problematic. These employ either epoxy-methoximes, vinyl-substituted oxiranes, or hydroxymethyl oxiranes.

Useful catalytic enantioselective cationic double annulation reactions initiated at an internal π-bond: method and applications.

The 1:1 complex of o,o'-dichloro-R-BINOL and SbCl5 initiates the enantioselective cationic polycyclization of polyunsaturated substrates at a predictable π-bond which may be either terminal or, as shown herein, internal. The extension of this powerful construction to internal π-bonds expands the scope of this method and opens up very short pathways to numerous chiral polycyclic molecules, including natural products and their analogues. Especially simple synthetic routes are disclosed that provide access to dysideapalaunic acid, dehydroabietic acid, and epipodocarpic acid and illustrate the value of this enantioselective approach.

Total synthesis of nhatrangin A.

A concise and stereoselective approach for the synthesis of key intermediates for aplysiatoxins, oscillatoxins, and nhatrangins and their utility for the total synthesis of nhatrangin A has been demonstrated. The advanced intermediates aromatic aldehyde 11 and dihydroxy acid 12 were synthesized in eight steps (44% overall yield) and three steps (55% overall yield), respectively. An asymmetric Michael addition, CBS reduction, and proline-catalyzed crossed-aldol reactions were utilized as key steps for the generation of all the chirality of main chain hydroxyaldehyde, while the appended side-chain-protected 3,4-dihydroxypentanoic acid was achieved in a shortest route, using Sharpless dihydroxylation, diol protection, and RuO4-catalyzed aromatic over-oxidation reactions.

Short route to platencin.

The synthesis of the complex tricyclic core of the terpenoid antibiotic platencin is achieved in a concise, protecting group-free and stereoselective manner. A flexible approach that highlights the intramolecular aldol reaction as the key step toward the construction of the bicyclo[2,2,2]octane ring from an angular allyl decalone in both the trans-fused and the cis-fused forms is demonstrated.