One-pot syntheses

Wong s strategy is but one of many aimed at synthesizing sugars on demand. Other chemists are using a variety of techniques—virtually all of which rely upon the use of protecting groups. 

Technology, constantly finds himself caught up in sticky situations. 

CH What are some of the things sugars do that make them so interesting to study  

Sasisekharan Sugars are like clothes cells wear. Which sugar coat a cell wears—for example a wool coat or a T-shirt—affects how that cell perceives and responds to its environment. The sequence of a sugar chain can influence the job a cell performs. I hope the day will come that we can tell cells what to wear—so that by having cells wear the right clothes at the right time, we can influence what cells do  

CH You ve recently discovered a way to decipher the sequence of long chains of sugars—how do you do it  

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Dear readers please take notice Not once has the flask left the stirplate since the formamide and P2P reaction started up to the last point where MDA freebase was liberated. That s pretty damn convenient. Technically, the Leuckart reaction can continue as a one pot synthesis from the last part of P2P cleanup right up to final product. 

In this preparation, phenyi-2-nitropropene is reduced to phenyl-2-nitropropane with sodium borohydride in methanol, followed by hydrolysis of the nitro group with hydrogen peroxide and potassium carbonate, a variety of the Nef reaction. The preparation is a one-pot synthesis, without isolation of the intermediate. 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

Pubhcations have described the use of HFPO to prepare acyl fluorides (53), fluoroketones (54), fluorinated heterocycles (55), as well as serving as a source of difluorocarbene for the synthesis of numerous cycHc and acycHc compounds (56). The isomerization of HFPO to hexafluoroacetone by hydrogen fluoride has been used as part of a one-pot synthesis of bisphenol AF (57). HFPO has been used as the starting material for the preparation of optically active perfluorinated acids (58). The nmr spectmm of HFPO is given in Reference 59. The molecular stmcture of HFPO has been deterrnined by gas-phase electron diffraction (13). 

Higher nitroalkanes are prepared from lower primary nitroalkanes by a one-pot synthesis (69). Successive condensations with aldehydes and acylating agents are followed by reduction with sodium borohydride. Overall conversions in the 75—80% range are reported. 

A new variant of the three-component, one-pot synthesis of L-foUc acid has been reported by Hoffmann-La Roche Inc. 

Although not of industrial importance, many organometallic approaches have been developed (38). A one-pot synthesis of vitamin has been described and is based on the anionic [4 + 2] cycloaddition of three-substituted isoben2ofuranones to l-phytyl-l-(phenylsulfonyl)propene. Owing to the rather mild chemical conditions, the (H)-stereochemistry is retained (39). 

The one-pot synthesis of 9 described above appears to afford only modest yields of azacrowns. One might wonder why any crown at all would be formed under non-high dilution conditions intended to yield only open-chained material. Vogtle suggests that this can be explained in terms of template, steric and entropy effects . These factors are of doubtless significance, but it is interesting to note that in the synthesis of poly-azamacrocycles, Richman and Atkins found that there was no significant template effect observed. The question of the template effect in Ihe syntheses of 9 has recently been addressed by Kulstad and Malmsten They conclude that the formation of 9 is assisted by the presence of alkali metal cations. 

A one-pot synthesis of alkyl perfluoroalkyl ketones has been developed. Phosphoranes, generated in situ, are acylated with a perfluoroacyl anhydnde, and the resultmg phosphonium salts are hydrolyzed with alkali [4S (equation 48) Hydrolysis of a carbon-sulfur bond in 2-chloro-2,4,4-trifluoro-1,3-dithietane-S-trioxide, which can be obtained from 2,2,4,4-tetrachloro-l,3-dithietane by fluor-mation with antimony trifluoride followed by selective oxidations, opens the nng to produce 2-chloro-1,1,2-trifluorodimethyl sulfone [49] (equation 49)... 

Oxidation of 4H-pyran-4-thiones with thallium(III) trifluoroacetate was used in the one pot synthesis of l,6-dioxa-6n-thiapentalenes, a hypervalent heterocyclic system [57] (equation 27)... 

This reaction gives good results for a variety of activated and unactivated alkyl halides [112] Oxidation of 2-bromoketones with iV-phenyltriflamide was used m a one pot synthesis of pyrazines by the sequence of reactions shown m equation 57 [II3] The procedure was successfully applied to the synthesis of deoxyaspergilhc acid [II4 ... 

A simple and elegant one-pot synthesis of 3-amino-4-arylfurazans from the corresponding aroyl cyanides was developed by Lakhan and Singh (Scheme 102) [87IJC(B)690]. 

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

Due to their successful synthesis of 2-(4 -chlorophenyl)-4-iodoquinoline from the corresponding precursor acetylene, Arcadi et al. (99T13233) developed a one-step synthesis of 2,4-disubstituted quinolines via palladium-catalyzed coupling reactions. An example is the Heck reaction of 4-iodoquinoline (131) with a-acetamidoacrylate (132). This one-pot synthesis yielded adduct 133 in 50% overall yield after purification via flash chromatography. 

A novel one-pot synthesis of ct-nitro ketones from alkenes has been observed 01 with trimethylsilyl nitrate-chromium trioxide or a trimeihylsilyl nitrate-DMSO reagent system fEq. 2.44. ... 

Far superior yields of l-(arylsulfonyl)-l//-azepines 16 are now available by a one-pot synthesis involving the action of sodium azide on an arylsulfonyl chloride under solid-liquid phase-transfer conditions which prevents the formation of acidic sulfonamides and, hence, the ring-contraction process.75 This procedure also has the advantage of avoiding the use of high pressures and the isolation and handling of the potentially explosive sulfonyl azides. 

Complex 25 was also used in an efficient one-pot synthesis of ruthenium-based precatalysts developed by Werner et al. [17a,b] it is generated in situ from RuCl3, H2, PCy3, magnesium, and 1,2-dichlorethane. Upon reaction of 25 with... 

Thiophenes are less reactive than furans and therefore react with very reactive dienophiles. They behave somewhat differently from furans and in many cases the intermediate addition products are unstable and undergo cheleotropic extrusion of sulfur [30]. Thiophenes 30 undergo cycloaddition reactions with DMAD (Equation 2.11) to afford bicyclic cycloadducts which lead to phthal-ates by sulfur extrusion, thus offering a one-pot synthesis of dimethylphthalates [31]. 

Phenylsulfonyl-1,3-dihydrospiro[2//-benzimidazole-2, l -cyclohexan]-5-amine (601) gave 7-phenylsulfonyl-6-quinoxalinamine (602) [Me0H-H20, 60°C, 20 min then (CH0)2-NaHS02i, 95°C, 5 min 55% clearly a two-stage one-pot synthesis via the unisolated intermediate shown] 7-morpholino-6-... 

Microwave irradiation has been used to accelerate the Gewald reaction for the one-pot synthesis of N-acyl aminothiophenes on solid support [67]. A suspension of cyanoacetic acid Wang resin 35, elemental sulfur, DBU and an aldehyde or ketone 36 in toluene was irradiated for 20 min at 120 °C in a single-mode microwave synthesizer (Scheme 13). Acyl chloride 37 was added, followed by DIPEA, and the mixture was irradiated for 10 min at 100 °C. After cooling to room temperature, the washed resin was treated with a TEA solution to give M-acylated thiophenes 38 in 81-99% yield and purities ranging from 46-99%. 

A one-pot synthesis of thiohydantoins has been developed using microwave heating [72]. A small subset of p-substituted benzaldehydes, prepared in situ from p-bromobenzaldehyde by microwave-assisted Suzuki or Negishi reactions, was reacted in one pot by reductive amination followed by cyclization with a thioisocyanate catalyzed by polystyrene-bound dimethyl-aminopyridine (PS-DMAP) or triethylamine, all carried out under microwave irradiation, to give the thiohydantoin products in up to 68% isolated yield (Scheme 16). 

The one-pot synthesis of thiazolo[3,4-a]benzimidazoles has been reported using a microwave-assisted condensation-cyclization (see Scheme 17) of a substituted 1,2-diamine, substituted benzaldehyde and mercaptoacetic acid [74]. Heating the mixture at reflux for 12 min using a single-mode microwave reactor for the most part gave the fused benzimidazoles in improved yield and dramatically shorter times, when compared to classical conditions of heating at reflux in benzene for 24-48 h (Scheme 29). 

Benzothiazepines belong to the three classes of calcium channel blockers which are important cardiovascular drugs in the management of angina pectoris and hypertension. A diastereoselective one-pot synthesis of the trans-and ds-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-l,5-benzothiazepin-4-one nucleus, a key intermediate in the preparation of the calcium channel blocker Diltiazem, was carried out under microwave irradiation in an open vessel (Scheme 25). Control of the diastereoselectivity was achieved by vary-... 

A rapid and efficient one-pot synthesis of substituted 2(5H)-furanones has been reported starting from 3-hydroxy-3-methyl-2-butanone 88 and ethyl... 

A structurally related tetrameric macroheterocycle is compound 13 that is prepared in a one-pot synthesis (yield 64%) from salicylaldehyde and (3-aminophenyl)boronic acid in methanol (Fig. 4). Due to its insolubility it has been characterized only by mass spectrometry. If a substitutent is introduced at the imine function (R = Me, Ph), trimeric structures (14 and 15) are... 

In 1992, Oda et al. reported a one-pot synthesis of optically active cyanohydrin acetates from aldehydes, which were converted to the corresponding racemic cyanohydrins through transhydrocyanation with acetone cyanohydrin, catalyzed by a a strongly basic anion-exchange resin [46]. The racemic cyanohydrins were acetylated by a lipase from P. cepacia (Amano) with isopropenyl acetate as the acyl donor. The reversible nature of the base-catalyzed transhydrocyanation enabled continuous racemization of the unreacted cyanohydrins, thereby effecting a total conversion (Figure 4.21). 

Figure 10.15 Enzymatic one-pot synthesis of D-tagatose 1,6-bisphosphate based on the stereoselective TagA m coli.

A Facile One-Pot Synthesis of MSe (M = Cd orZn) Nanoparticles Using Biopolymer as Passivating Agent... 

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