Search results
Search for "C1 building blocks" in Full Text gives 3 result(s) in Beilstein Journal of Organic Chemistry.
Formaldehyde surrogates in multicomponent reactions
- Cecilia I. Attorresi,
- Javier A. Ramírez and
- Bernhard Westermann
Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45
- controlling the formation of undesired byproducts during its reactions. This review explores alternative C1-building blocks that serve as surrogates for formaldehyde, aiming to mitigate some of the challenges associated with its use in multicomponent reactions. By identifying these alternatives, toxicity
- devoted to dimethyl sulfoxide, dihalomethanes, hexamethylene tetramine, and glyoxylates as C1-building blocks, substituting formaldehyde. Review Methanol as a source of formaldehyde There are several reports on the use of alcohols under oxidative conditions as aldehyde surrogates in Ugi and Passerini
- nucleophilic reactions or as methylene sources in electrophilic reactions [53][54][55][56][57]. In the latter case, they are employed as C1 building blocks, with abundant examples in the literature [55][56][57]. This section will focus on the most important uses of dihalomethanes as formaldehyde alternatives
Graphical Abstract
Scheme 1: Features of the ideal reaction (redrawn from P. A. Wender et al. [1]).
Scheme 2: Some of the most popular MCRs with formaldehyde as the carbonyl component.
Scheme 3: Ugi reaction under a catalyzed electro-oxidation process using TEMPO (2,2,6,6-tetramethyl-1-piperid...
Scheme 4: Examples of different products obtained by MCRs in which DMSO serves as -SCH3 source.
Scheme 5: Mechanism of the decomposition of DMSO under acidic or thermal conditions. a) In situ generation of...
Scheme 6: Povarov multicomponent reaction to quinolines.
Scheme 7: Example of the Povarov reaction with formaldehyde with a julolidine derivative as main product.
Scheme 8: Povarov multicomponent reaction to quinoline derivatives I and II using DMSO as formaldehyde surrog...
Scheme 9: Example of a Povarov three-component reaction with change of catalyst, yielding regioisomer III. In...
Scheme 10: The Povarov three-component reactions carried out under acidic catalysis to afford quinoline regios...
Scheme 11: Different MCR routes involving DMSO to synthesize complex heterocycles such as diarylpyridines and ...
Scheme 12: Pyrazole synthesis by a three-component reaction using DMSO as a source of a C-1 unit.
Scheme 13: Three-component reactions for the synthesis of aliphatic heterocycles 13 and 14 using DMSO as a for...
Scheme 14: Proposed mechanism for the 3CR between homoallylic amines, disulfides, and DMSO.
Scheme 15: Mannich-type reaction using DMSO as formaldehyde surrogate.
Scheme 16: Mechanism for the 3CR-Mannich-type reaction between aryl ketone 18, saccharine (19), and DMSO. The ...
Scheme 17: Mannich-type reaction using DMSO as formaldehyde surrogate and under oxidative activation.
Scheme 18: Three-component reaction between an indazole, a carboxylic acid, and DMSO.
Scheme 19: Amine–aldehyde–alkyne (AAA) coupling reaction and plausible mechanism.
Scheme 20: AHA coupling for the synthesis of propargylamines using dihalomethanes as C1 building blocks.
Scheme 21: AHA coupling using CH2Cl2 as both solvent and methylene source.
Scheme 22: Examples of propargylamines synthesized under catalytic AHA protocols.
Scheme 23: Proposed mechanism for the synthesis of propargylamines using dichloromethane as a C1 source.
Scheme 24: Mechanism proposed for the generation of the aminal intermediate E by Buckley et al. [68].
Scheme 25: Pudovic and Kabachnik–Fields reactions for the synthesis of α-aminophosphonates.
Scheme 26: a) Abramov side reaction that generates α-hydroxy phosphonate as a byproduct during the Kabachnik-F...
Scheme 27: Catalyst-free three component reaction to afford α-amino phosphorus product 35 using 1,1-dihaloalka...
Scheme 28: a) Proposed mechanism for the three-component reaction of dichloromethane, amine and phosphorus com...
Scheme 29: Ugi-ammonia strategy using HMTA as a formaldehyde surrogate.
Scheme 30: Glyoxylate and its derivatives as C1 building blocks.
Scheme 31: The Groebke–Blackburn–Bienaymé multicomponent reaction (GBB) and its mechanism.
Scheme 32: a) Byproducts in the GBB multicomponent reaction (GBB) when formaldehyde is used as the carbonyl co...
Scheme 33: Possible regioisomers in the GBB multicomponent reaction when formaldehyde is used as the carbonyl ...
Scheme 34: The multicomponent GBB reaction yields 2-unsubstituted 3-aminoimidazo heterocycles 42a using MP-gly...
Scheme 35: GBB multicomponent reaction to 2-unsubstituted 3-amino imidazo heterocycles 42a using glyoxylic aci...
Scheme 36: GBB reaction using glyoxylic acid immobilized on silica as formaldehyde surrogate.
Scheme 37: Bioactive products synthesized by the GBB reaction using glyoxylic acid.
Scheme 38: van Leusen three-component reaction to imidazoles.
Scheme 39: Side reaction during the synthesis of imidazoles with formaldehyde as the carbonyl compound.
Scheme 40: Optimization of the van Leusen three component reaction to 1,4-disubstituted imidazoles 43 using gl...
Scheme 41: Application of the Sisko strategy [96] for the synthesis of CB1 receptor antagonist compounds [97].
Scheme 42: Side reaction, when NH4OH is used as amine component.
Scheme 43: Ugi-type adducts with the ester moiety and the acidic CH to be used for post-cyclization sequences.
Scheme 44: Ugi/cycloisomerization process to pyrrolones 51, butenolides 52, and pyrroline 53.
Scheme 45: Radical cyclization reactions from Ugi adducts promoted by TEMPO.
Scheme 46: Hydrolysis and decarboxylation reactions to products with incorporation of a C1 unit of ethyl glyox...
Scheme 47: One-step synthetic route to pyrrolones 60 using phenylglyoxal.
Scheme 48: Ugi-pseudo-Knoevenagel-pseudo-Dieckmann cascade sequence for the synthesis of fused heterocycles.
Scheme 49: Ugi-pseudo-Knoevenagel reaction from ethyl glyoxylate.
Methylidynetrisphosphonates: Promising C1 building block for the design of phosphate mimetics
- Vadim D. Romanenko and
- Valery P. Kukhar
Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114
- , structure, reactions, and potential medicinal applications of these compounds. Keywords: biomimetic synthesis; C1 building blocks; phosphorylation; polyphosphonates; synthetic methods; Introduction Methylidynetrisphosphonic acid, HC(PO3H2)3, or more commonly methylidynetrisphosphonates, XC(PO3R2)3, also
Graphical Abstract
Scheme 1: Synthesis of hexaethyl dialkylaminomethylidynetrisphosphonates 1 from dichloromethylene dialkylammo...
Scheme 2: Synthesis and some transformations of trisphosphonate 2.
Scheme 3: Attempt to synthesize trisphosphonates by the combination of Arbuzov reaction and dialkyl phosphite...
Scheme 4: Synthesis of hexaethylmethylidynetrisphosphonate 6 via phosphinylation of tetraethyl methylenebisph...
Scheme 5: Synthetic approach to methylidynetrisphosphonate ester 9.
Scheme 6: Synthesis of alkylidyne-1,1,1-trisphosphonate esters 12.
Scheme 7: Two-step one-pot synthesis of propargyl-substituted trisphosphonate 15.
Scheme 8: Synthetic route to trisphosphonate 18 via 7,7-bisphosphonyl-3,5-di-tert-butylquinone methide 17.
Scheme 9: Synthesis of trisphosphonate 18 starting from 2,6-di-tert-butyl-4-(dichloromethyl)phenol.
Scheme 10: Synthesis of triphosphorus derivatives 20 via quinone methides 17 and 19.
Scheme 11: Unexpected phosphonylation of the aromatic nucleus in reactions of quinone methides 19 and 21.
Scheme 12: Multistep synthesis of trisphosphonate 18 starting from quinone methide 25.
Scheme 13: Synthesis of hexaethyl methylidynetrisphosphonate (6) via metal-carbenoid-mediated P–H insertion re...
Scheme 14: Reaction between tert-butylphosphaethyne and diethyl phosphite in the presence of sodium metal.
Scheme 15: Cross metathesis of trisphosphonates 12 with 2-methyl-2-butene and the Grubbs second-generation cat...
Scheme 16: Hydroboration–oxidation of trisphosphonates 12b,e.
Scheme 17: Reaction of 3-butyn-1-ylidenetrisphosphonate 15 with benzyl azide.
Scheme 18: The use of the transsilylation reaction for the synthesis of trisphosphonate salts 37.
Scheme 19: Synthesis of the sodium salt of the acid-labile trisphosphonic acid 38.
Scheme 20: Acidic hydrolysis of trisphosphonate ester 1a.
Scheme 21: Methylation of trisphosphonate 1a.
Scheme 22: Synthesis of the free methylidynetrisphosphonic acid via trisphosphonate salt 38.
Scheme 23: Synthesis of halomethylidynetrisphosphonate salts 43 and 44 by modified Gross’s procedure.
Scheme 24: Synthesis of trisphosphonate modified nucleotides. Reagents: i, 5'-O-tosyl adenosine, MeCN; ii, AMP...
Figure 1: Bond angles and bond distances in pyrophosphate, methylene-1,1-bisphosphonate and fluoromethylidyne...
Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine
- Marc Enßle,
- Stefan Buck,
- Roland Werz and
- Gerhard Maas
Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49
- ][6][7][8] illustrate the wide range of applications. As far as sulfonium ylides are concerned, thermally induced isomerisation, that is the 1,2-shift of a substituent (Stevens rearrangement) and [2,3]-sigmatropic rearrangement of allylsulfonium ylides [9][10][11], and the use as C1 building blocks in
Graphical Abstract
Scheme 1: Synthesis of cyclic sulfonium ylides 2; n = 0–3.
Scheme 2: Non-carbenoid formation of sulfonium ylide 4.
Scheme 3: Conditions: (a) phthalic anhydride, NEt3 (10 mol %), toluene, reflux, 2 h; (b) 1. carbonyldiimidazo...
Scheme 4: Rh(II)-catalysed carbenoid reactions of diazoesters 8a,b.
Figure 1: Proposed relative configurations of the diastereomeric cyclic sulfonium ylides 12aA and 12aB. 1H NM...
Scheme 5: Endo transition state for [3 + 3]-dimerisation of carbonyl ylide 14.
Scheme 6: Rh(II)-catalysed carbenoid reactions of diazoester 8c.
Scheme 7: Tandem cyclisation/intermolecular cycloaddition of diazoester 8a. Conditions: (a) Rh2(OAc)4 (3 mol ...
Scheme 8: Carbenoid formation of sulfonium ylides from diazoesters 11a,b. Conditions: (a) Rh2(OAc)4 (3 mol %)...
