Asymmetric multicomponent reactions involve the preparation of chiral compounds by the reaction of three or more reagents added simultaneously. This kind of addition and reaction has some advantages over classic divergent reaction strategies, such as lower costs, time, and energy, as well as environmentally friendlier aspects. All these advantages, together with the high level of stereoselectivity attained in some of these reactions, will force chemists in industry as in academia to adopt this new strategy of synthesis, or at least to consider it as a viable option. The positive aspects as well as the drawbacks of this strategy are discussed in this Review.

Asymmetric multicomponent reactions (amcrs): the new frontier

6.1. Oxadiazoles 4154 6.2. Diazaphospholes 4154 7. Six-Membered Heterocycles with One Heteroatom 4155 7.1. Pyridines 4155 7.2. Pyridinones 4155 7.3. Quinolines 4156 7.4. Quinolinones 4157 7.5. Isoquinolines 4157 7.6. Acridines 4158 7.7. Pyranones 4158 7.8. Flavones 4159 8. Six-Membered Heterocycles with Two Heteroatoms 4159 8.1. Pyridazinones 4159 8.2. Pyrimidines 4159 8.3. Pyrimidinones 4160 8.4. Quinazolines 4162 8.5. Quinazolinones 4162 8.6. Quinoxalines 4164 8.7. Quinoxalinediones 4165 8.8. Oxazines 4165 8.9. Oxazinones 4166 8.10. Thiazines 4166 9. Six-Membered Heterocycles with Three Heteroatoms 4166

Solvent-free heterocyclic synthesis.

Since about the year 2000, the research area of asymmetric organocatalysis has grown rapidly to become one of the most fascinating and current fields in organic chemistry. In the last years, asymmetric domino reactions have widely benefited from this fast-growing field, as exemplified by the development of an explosive number of novel and powerful asymmetric organocatalytic domino processes, which allowed the easy construction of complex chiral molecular architectures from simple materials with high yields and very often remarkable enantioselectivities in a metal-free environment. Indeed, the possibility to join two or more organocatalytic reactions in one asymmetric domino process has become a challenging goal for chemists, due to several advantages from economical and environmental points of view, avoiding costly protecting groups and time-consuming purification procedures after each step, for example. This review aims to update the latest developments of this hot and fascinating field, covering the literature since the beginning of 2009. 

Abbreviations: Ac: acetyl; Ar: aryl; BDHP: 1,1′-binaphth-2,2′-diyl hydrogen phosphate; BA: Bronsted acid; BINAPO: 2-diphenylphosphino-2′-diphenylphosphinyl-1,1′-binaphthalene; BINOL: 1,1′-bi-2-naphthol; Boc: tert-butoxycarbonyl; Bn: benzyl; Bu: butyl; Bz: benzoyl; CSA: camphorsulfonic acid; Cy: cyclohexyl; Cbz: benzyloxycarbonyl; DABCO: 1,4-diazabicyclo[2.2.2]octane; DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; DCE: dichloroethane; de: diastereomeric excess; DFT: density functional theory; DHQ: hydroquinine; DHQD: dihydroquinidine; DIPEA: diisopropylethylamine; DKR: dynamic kinetic resolution; DMAD: dimethyl acetylenedicarboxylate; E: electrophile; ee: enantiomeric excess; ESI: electrospray ionization; Et: ethyl; Fu: furyl; Hept: heptyl; Hex: hexyl; HOMO: highest occupied molecular orbital; IBX: o-iodoxybenzoic acid; LB: Lewis base; LUMO: lowest unoccupied molecular orbital; Me: methyl; MOM: methoxymethyl; Mes: mesyl; MS: mass spectroscopy; MTBE: methyl tert-butyl ether; NADH: nicotinamide adenine dinucleotide; Naph: naphthyl; NHC: N-heterocyclic carbene; NMM: N-methylmorpholine; NMP: N-methylpyrrolidinone; Ns: nosyl; Nu: nucleophile; Oct: octyl; PCC: pyridinium chlorochromate; Pent: pentyl; PFBA: pentafluorobenzoic acid; Ph: phenyl; PMB: para-methoxybenzyl; Pr: propyl; Py: pyridine; r.t.: room temperature; TBA: tribromoacetic acid; TBS: tert-butyldimethylsilyl; TCBA: 2,4,6-trichlorobenzoic acid; TES: triethylsilyl; TFA: trifluoroacetic acid; THF: tetrahydrofuran; Thio: thiophene; TMEDA: tetramethylethylenediamine; TMS: trimethylsilyl; Tol: tolyl; Ts: 4-toluenesulfonyl (tosyl).

Recent Developments in Asymmetric Organocatalytic Domino Reactions

Transition metal catalyzed denitrogenative transannulation of a triazole ring has recently received considerable attention as a new concept for the construction of diverse nitrogen-containing heterocyclic cores. This method allows a single-step synthesis of complex nitrogen heterocycles from easily available and cheap triazole precursors. In this Minireview, recent progress of the transition metal catalyzed denitrogenative transannulation of a triazole ring, which was discovered in 2007, is discussed.

/pdf/transition-metal-catalyzed-denitrogenative-transannulation-2kzjw51ipv.pdf

Transition-Metal-Catalyzed Denitrogenative Transannulation: Converting Triazoles into Other Heterocyclic Systems

Recent advances in pyridine synthesis are described. Modification of traditional condensation strategies continues to be a recurrent theme in contemporary literature. Advancements in transition-metal-catalyzed cyclization and cross-coupling procedures offer new routes to functionalized pyridine derivatives. These recently developed methodologies are a valuable addition to azaheterocycle synthesis.

Recent Strategies for the Synthesis of Pyridine Derivatives

Knoevenagel's first papers in this field were concerned with the condensation of formaldehyde with diethyl malonate and with ethyl benzoylacetate. The catalyst was ethylamine. A number of other aldehydes were reported to condense similarly with diethyl malonate, ethyl benzoylacetate, ethyl benzoylpyruvate, and acetylacetone under the influence of various primary and secondary amines. In 1896, Knoevenagel reported benzaldehyde with ethyl aceoacetate condensed at room temperature in the presence of piperdine to give a bis compound, but that when the reaction was run in a freezing mixture, the product was acetoacetate. For the purposes of this chapter, the Knoevenagel condensation is defined as the reaction between an aldehyde or ketone or any compound having an active methylene group, brought about by an organic base or ammonia and their salts.


Keywords:

Knoevenagel condensations;
decarboxylation;
malonic acid;
active methylene component;
stereochemical aspects;
cyanoacetic acid;
ketones;
derivatives. caatalysts;
experimental conditions

The Knoevenagel Condensation

5.05 – Pyridines and their Benzo Derivatives: Synthesis

The chemistry of the triazolopyridines: an update

Triazolopyridines. 18. Nucleophilic substitution reactions on triazolopyridines; a new route to 2,2′-bipyridines☆

This chapter extends the discussion to reactions between the Vilsmeier-Haack reagent (subsequently referred to as the Vilsmeier reagent for brevity) and any other compounds in which a carbon-carbon bond is formed. The discussion thus excludes reactions in which the Vilsmeier reagent acts as a chlorinating agent (for example in the preparation of acid chlorides), or in which it forms carbon-oxygen or carbon-nitrogen bonds, unless these are accompanied by formation of a carbon-carbon bond. For a discussion of the nature of the reagent and of the mechanism of the reaction, the earlier chapter in vol. 49 should be consulted. There are also a number of reviews that deal at length with mechanisms of reactions involving the Vilsmeier reagent, notably those by Jutz and Marson, and hence this chapter will concentrate on applications, with brief mention of mechanisms when necessary.



Wizinger has pointed out that alkenes could react with the Vilsmeier reagent, but his only examples were styrenes where the intermediate carbocation has considerable stability.



Hydrolysis gives the cinnamaldehyde. In principle, any alkene which is not too sterically hindered can undergo this reaction, but the Vilsmeier reagent has low reactivity as an electrophile, and in practice activation is often necessary. The addition depends on the HOMO of the alkene, and anything increasing the HOMO energy will aid reaction, as for example further conjugation (dienes, trienes, etc.) or the presence of an electron-donating substituent. Hence aldehydes and ketones are active in their enol forms, and enol ethers and enamines are good substrates. Indeed, all additions covered by this chapter can be regarded as alkene additions, even those on active methyl groups attached to electron-deficient rings. As with any reaction involving carbocation intermediates, rearrangements are possible; the initial products are sometimes enamines, and this can give rise to polysubstitution. The substrates are grouped into eleven major subsections; references to reviews of particular relevance will be found in the appropriate subsection.


Keywords:

vilsmeier reaction;
non-aromatics;
alkenes;
dienes;
polyenes;
heteroatoms;
substituents;
enamines;
enamides;
alkynes;
aldehydes;
ketones;
imines;
hydrazones;
semicarbazones;
oximes;
carboxylic acids;
anhydrides;
acid chlorides;
esters;
lactones;
amides;
lactams;
imides;
nitriles;
methyl groups;
methylene groups;
adjacent rings;
comparison of methods;
experimental conditions;
experimental procedures;
tabular survey

Gurnos Jones

Papers

The Knoevenagel Condensation

5.05 – Pyridines and their Benzo Derivatives: Synthesis

The chemistry of the triazolopyridines: an update

Triazolopyridines. 18. Nucleophilic substitution reactions on triazolopyridines; a new route to 2,2′-bipyridines☆

The Vilsmeier Reaction of Non‐Aromatic Compounds