Recent Developments in Weinreb Synthesis and Their Applications

Introduction

N-methoxy-N-methylamides or Weinreb amides become a worthy synthetic precursor in organic synthesis.¹ The first synthesis of Weinreb moiety was reported in 1981.² This reaction called Weinreb amidation, included preparation of N-methoxyl-N-methyl amides from N,O-dimethyl hydroxylamine using AlMe₃ as a coupling reagent. Thereafter, diverse access for the synthesis of Weinreb amides has been announced, such as direct transformation of carboxyl group into the equivalent ketone or aldehyde. Remarkably, the efficiency of Weinreb intermediate to submit a single substitution reaction with excess organometallic reagents is essential to its publicity as acylating agents ³ in the laboratory and industrial synthesis processes. Weinreb intermediate could neatly react with organolithium,⁴ Grignard reagents,⁵ and LiAlH₄⁶ to produce aldehydes or ketones newly; it could react with Wittig reagents to yield ketones.⁷ Nowadays, much effort has been dedicatedto the way to develop their soft and universal synthesis. Such, Weinreb amides can be synthesized from carboxylic acids⁸, acid chlorides,⁹ amides, ¹⁰ esters,¹¹ lactones,¹² and anhydrides.¹³ Furthermore, the easy transformation of carboxylic acids to the Weinreb amides is much more attractive.

Due to the fast development of Weinreb amidessynthesis and their applicationsin the last ten years, it was motivating to reviewwhole the recently published papers in the period from 2010 up to 2019 and details some neoteric developments of these strategy processes.

In 2010, Jang and co-workers¹⁴describeda flexible one-pot process for the synthesis of Weinreb amides from carboxylic acids using trichloroacetonitrile (TCA) and triphenylphosphine (TPP) (Scheme 1). Here, the authors presumed that carboxylic acid chlorides generatedin situthrougha combination of carboxylic acids 1with TCA and TPP, followed by treatment with N,O-dimethylhydroxylamine in the presence of triethylamine (TEA) to produce the corresponding Weinreb amides.The feature of such reaction is that it can performsatisfactorily with various aliphatic and aromatic carboxylic acids, which showed asoft level to produce the desired products 2with high yields (75-93%).

Scheme 1 Click here to View Scheme

 

In parallel, Davis and Theddu¹⁵reported a new methodology forthe asymmetric synthesis of cyclic β-amino acid derivatives6viafive-, six-, and sevenring-closing metathesis of sulfinimine-derived N-sulfinyl β-amino diene Weinreb amides(Scheme 2). The protocol here described introducing N-sulfinyl β-amino Weinreb amides5, which furnished aninclusive solution to overcome the problem of enantiopure β-amino ketone and aldehyde synthesis. However, the addition of Weinreb amide enolates4to sulfinimines (N-sulfinyl imines)3 was used for the first time to prepare N-sulfinyl β-amino Weinreb amides.

Scheme 2 Click here to View Scheme

 

Furthermore, Aidhenand co-workers¹⁶detailed facile synthesis of N-methoxy-N-methyl-N-phenylsulfonylglycinamide and N-methoxy-N-methyl-N-benzyl-N–tert-butyloxy carbonyl glycinamide equivalents using Weinreb amide functionality, which considered a valuable route for the universal synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinolinederivatives(Scheme 3). Uncommonly, the two normal reactions,N-benzylation and addition of arylmagnesium halide 8on the Weinreb amide7, deigned thekey intermediate 9for suitable synthesis of 4-aryl-1,2,3,4-tetrahydroisoquinolines11in high yields (97-99%).

Scheme 3 Click here to View Scheme

 

Furthermore,Herr and co-workers ¹⁷detailed the efficient role of palladium-catalyst in preparation of benzamides16and α,β-unsaturated Weinreb amides15using organoboronicacids (12or 13)and N-methyl-N-methoxycarbamoylchloridesubstrate14(Scheme 4). Under optimization conditions, using potassium phosphate monohydrate as a base and dry ethanol as a solvent at 65 ºC, the key incorporation between the substrates with the palladium catalyst, confirmed one-pot synthesis of the expected products. Variety of aromatic organoboronic acids bearing electron-withdrawing and electron-donating groups, displayed a widemanner toward the reactionconditions.

Scheme 4 Click here to View Scheme

 

Furthermore, Lakshman and co-workers¹⁸ illustrated an effective transformation of carboxylic acids to the corresponding secondary, tertiary, and Weinreb amidesusingPPh₃/I₂or Pol–PPh₃/I₂(Scheme 5). The mechanism the strategy firstly, proceeds through combination between PPh₃ and I₂in a 1:1 ratio, produced a newspecies represented by (Ph₃P⁺–I)I^–. The latterqualified to react with carboxylic acids 17in presence of iPr₂NEtand form either an acyl phosphonium species 17ior an acyl iodide17ii. The reaction of the resultants with the amine18, produce the final amide products19.

Scheme 5 Click here to View Scheme

 

In 2011, Odell and co-worker ¹⁹represented a direct methodology for the synthesis of Weinreb and MAP aryl amides via Heck amino carbonylation under microwave irradiation process (Scheme 6). The protocol of such reactions proceed through treatment of hetero-aryl bromides and iodides20with (21 or 22), Pd(OAc)₂catalyst, Xantphos ligand,W(CO)₆ or Mo(CO)₆as the CO source andK₃PO₄base in dioxane solvent for 30 minutes under the microwave irradiation. Differentfunctional groups were tolerated and the expected products (23and 24) were obtained in good yields. The achievements of these protocols are quite determined and insuretheir low cost, short time, andthe generation of toxic CO-gas in situ.

Scheme 6 Click here to View Scheme

 

Later, Aidhen and co-worker ²⁰ drew a novel strategy for the synthesis of equivalent, including Weinreb amide as a backbone for general synthesis of 1,1-diarylethenes and particularly synthesis of isocombretastatin30starting from glyoxalic acid substrate25(Scheme 7). The appropriateness which thestructural diversity can be made in combing the aryl remains provided mostrelatedtothe improvement protocol. Furthermore, the intermediates (26-29) supplied oncoming to 1,2,2-triarylethanones, performed bythe synthesis of progressive intermediate of tamoxifen.

Scheme 7 Click here to View Scheme

 

Meanwhile, Pelkey and co-worker ²¹reported a new protocol for the synthesis of symmetrical and unsymmetrical 3,4-Diaryl-3-pyrrolin-2-ones (Scheme 8).This synthesis proceeds steadily via reactions between β-nitrostyrenes and pyrrole-2-carboxamides (pyrrole Weinreb amides)utilizing as the keyintermediates. The authors suggested two reaction pathways for preparation of nitroalkenes: Firstly, Henry reaction modification between arylnitromethanes33 and arylimines34(method ≠1),and secondly, Suzuki-Miyauracross-coupling reaction of 2-aryl-1-bromo-1-nitroethenes 36with arylboronic acids(method ≠2).Furthermore, Barton-Zardpyrrole cyclo condensation process between 1,2-diaryl-1-nitroethenes 35and N-methoxy-N-methyl-2-isocyanoacetamide38, afforded synthesis of pyrrole Weinreb amides39, followed by transformation to the corresponding 3,4-diaryl-3-pyrrolin-2-one compounds 41over two steps. One of the applications of such reaction was preparation eight 3,4-diaryl-3-pyrrolin-2-ones containing the N-H lactam peer of rofecoxib.

Scheme 8 Click here to View Scheme

 

While Tyrrell and co- worker ²²detailed the efficient transformation ofα-amino acids to Weinreb amides using(COMU) asa coupling agent(Scheme 9).Generally, a mixture ofN-protected α-amino acids42and N-methoxy-N-methylamine hydrochloride43 in presence of COMU, and DIEA in DMF at 0 ºC, afforded Weinreb amide products44 in high yields (63-97%). Because the by-products of the reaction are handilywater-soluble, the products are separated comparatively pure and with lower racemization.

Scheme 9 Click here to View Scheme

 

Independently, Guogroup²³has detailed the importance role of [Ru((S)-Sunphos)(benzene)Cl]Cl as the catalyst and CeCl₃·7H₂O as the additive in the asymmetric hydrogenation of α-keto Weinreb amides(Scheme 10). Normally, the ratio of CeCl₃·7H₂O to [Ru((S)-Sunphos)(benzene)Cl]Cl displayed the significant function in the hydrogenation reaction. It is remarkable that different functional groups in α-keto Weinreb amides45were screened and resulted an obvious scope toward the reaction conditions, giving the desired α-hydroxy Weinreb amide products (46 and 47) in high yields (up to 97% ee).

Scheme 10 Click here to View Scheme

 

In 2013, a straightforward access to the synthesis of benzimidazoles and benzothiazoles 50 in one pot was described by Rangappa group²⁴(Scheme 11).This reaction proposed to proceed clearlyvia a condensation reaction between Weinreb amide 49and (o-diaminoarene or o-aminothiophenol) 48, followed by cyclization process in present of boron trifluoride etherate in dioxane solvent at 100 ºCfor 60 minutes. This optimal condition displayed the efficient role of Weinreb amide substrate 49toward the cyclization process, even in presence of other energetic functional groups like methoxy, carboxyl, cyano and halogen. However, using one pot synthesis shows the Weinreb amide high selectivity in the reaction.

Scheme 11 Click here to View Scheme

 

Later, Pace and co-workers ²⁵announced a new novel protocol for the synthesis of Weinreb amidesbeginning from readily available obtainable acid halides51using N,O-dimethylhydroxylamine hydrochloride (DMHA)52in the biphasic medium 2-MeTHF/H₂O (Scheme 12).Virtually, this method afforded pure products53 with excellent yields after simply remove of 2-MeTHF and no need to further organic solvents in the purification step. Moreover, the different substituents on the acid halide framework, containing electron withdrawing group and electrondonating group, were tolerated and revealedhighly effective substrates, leading to the pure products53.

Scheme 12 Click here to View Scheme

 

Later, functionalization of Weinreb amides to the corresponding asymmetric aldehydes and ketones containing chiral centers have been developed by Davies group²⁶ (Scheme 13). The authors suggested two synthetic routes to get the corresponding enantio pure aldehydes or ketones: Firstly, preparation of amide followed by hydride reduction or the addition reaction with organometallic reagent. Secondly, preparation of alcoholviareductive cleavage of the chiral auxiliary, followed then by re-oxidation reaction to produce the corresponding aldehyde. Actually, using chiral auxiliaries such as N-acyl derivativesqualified for functioning as potentialaldehyde and ketone products 57 and 58 through immediately cleavage of the auxiliary.

Scheme 13 Click here to View Scheme

 

In parallel anovel procedure for synthesis of N-protected α-amino/peptide Weinreb amides were described by Sureshbabu group²⁷(Scheme 16).  The protocol here depended on the reaction range of Fmoc, Boc or Cbz -protected amino acids 59with N,O-dimethylhydroxylamine substrate in presence of T3Pand DBUin CH₃CN at 0 ºC for 30 min. The key combination between T3P and DBU, affordedsuperior result and encouraged synthesis of the corresponding Weinreb amide products60.Furthermore,the molecular structure of Weinreb amide was characterized through X-ray crystallography.

Scheme 14 Click here to View Scheme

 

In 2014, Bhanage and co-workers detailed the effective role of Pd(OAc)₂/DABCO as catalyst under phosphine-free conditions in the synthesis of single and double Weinrebamides²⁸(Scheme 15).This process proceeds steadily through one-pot aminocarbonylationofaryl iodides61, Pd(OAc)₂, DABCO, Na₂CO₃,in CH₃CNunder an atmospheric pressureof carbon monoxide, to produce the corresponding products with excellent yields (83-95%).A reasonable mechanistic for this reaction forwardsviaThree main steps includes, oxidative addition with palladium (0), migratory insertionof CO, and finally, nucleophilic reaction with theN-methoxy-N-methyl amine moiety62to transform to the corresponding Weinerb amide product63.No need to expensive and sensitive phosphine ligandsand stability of DABCO ligand for the Pd(OAc)₂,werethe best advantages for such protocol.

Scheme 15 Click here to View Scheme

 

Next, Rahaim and co-workers ²⁹ revealed a modest application of titanium catalyst mediated there gioselective synthesis of Enones(Scheme 16).Normally, the reaction approved by the coupling reaction between unsymmetrical internal alkynes 64with Weinreb amides65, giving the trisubstituted enone products66 in reasonable chemoselectivityto good yields. It is noticeable that range of functional groups in Weinreb amides, function a wide amplitude toward the reaction conditions producing the relating products in moderate to excellent yields (51-95%).

Scheme 16 Click here to View Scheme

 

On the other side, Seayadand co-workers ³⁰incorporate version, highyielding and helpfulprocedure forsynthesis of Weinreb amides and ketones starting from aryl bromide or iodide substrates (Scheme 16). The protocol here, focused on the coupling reactions of aryl iodides or bromides 67with N,O-dimethylhydroxyaminehydrochloride69in the presence of Pd nanoparticles supported on ZIF-8 under comparatively direct aminocarbonylationconditions processes.  This methoddisplayedthe efficient role of palladium catalyst in the synthesis of diversefunctionalized Weinreb amides 70withperfect yields (75-98%). It is noteworthy that the catalyst Pd/ZIF-8 could be recovered and scale up potential was alsoproved in a gram scale achieving a 1000 of about 1500.

Scheme 17 Click here to View Scheme

 

On the other side, the synthetic and mechanistic studies of reductive of N–O bond cleavage of Weinreb amides promoted by sodium in aluminaand silica gels(Na-AG) and(Na-SG) has been studied by Jackson group³¹(Scheme 18).Generally, the clarity of such reactions, turn on under optimal conditions, is analogous with the protocols used for similarreactions using reagent such as SmI₂/THF at (-78 ºC), orLi/di-t-Butylbiphenylat (-78 ºC). In this work, various functional groups of Weinreb amides71were tested, demonstrated their obviously novel group transfer feature, implicationbase-utilized cleavageof the Weinreb amide to produce formaldehyde, followed by aldol condensation reaction. Furthermore, high reduction selectivity with simple Weinreb amide substrates was observed.

Scheme 18 Click here to View Scheme

 

In parallel,Wang and co-workers³²detailed the first uses of palladium catalyst in the directed C-H functionalization of Weinreb amides (Scheme 19).Normally, the reaction between either aryl Weinreb amides or benzyl amides 74and iodoarenes75in the presence of palladium acetate as the pre-catalyst in DCE solvent, encouraged transformation of expected final products76.A range of Weinreb amides containing bothelectron- withdrawing and -donating groups as well as halogen were exposedto the reaction conditions and demonstrated highly efficientsubstrates, leading to the desired products.

Scheme 19 Click here to View Scheme

 

Moreover, Yamamoto and co-workers ³³ described the novel usage of Ir(III) catalyst in the asymmetric intermolecular hydroarylation of arenes oriented by oxygen setup group (Scheme 20). Actually, this scope detailed an exclusive example of Weinreb Amide product 79employing the bidentatebis (phosphoramidite) ligand.

Scheme 20 Click here to View Scheme

 

Compared to the rapid development in the scope of C-H Functionalization process, Das and Kapur³⁴have used ruthenium as a rapid catalystin Fujiwara–Moritanior the oxidative-Heck reaction of Weinreb Amides (Scheme 21).This reaction mechanism suggested to forward simply through three main steps includes, coordination ofcarbonyl oxygen Weinreb amide substrate80with Ru^II, followed byC-H activation through carbometallation step and finally, β-hydride elimination and affording products 82with moderatetoexcellent yields(54–95%).Overall,awide variety of beneficial of activated olefins81 as well as styrenes istolerated under the mild conditions, capable a softcoupling partners.

Scheme 21 Click here to View Scheme

 

After one year, the same group published a paperutilizing the same Ru^II catalyst in synthesis of a newform of WeinrebamidesviaHeck or the oxidative-Heck reactions³⁵ (Scheme 22). Here, the reaction mechanism preceded first throughthe complexion between amide carbonyl oxygen group83 and cationic ruthenium complex by the regioselective oxidative C-H olefination. Generally, two diverse intermediates are probable, 5-membered ruthenacycle or 6-memberedruthenacycle.The high proportional stability of the 5-membered ruthenacycle intermediate, allowed it to coordinate with the olefin84, followed by β-hydride elimination to form the final product85. Meanwhile, mechanistic studies disclosed pleasant parts of thedirecting group abilities of simple structure Weinreb amides.

Scheme 22 Click here to View Scheme

 

Moreover, Wang and co-workers³⁶described a dynamic route for the synthesis of 2-Ns-Protected β-amino Weinreb amidesviaaminochlorination of α,β-unsaturated Weinreb amides in an ionic liquid, 1-n-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([BMIM][NTf₂])(Scheme 23).Generally, when this reaction transfers theionic liquid to [BMIM][NTf₂], it was shown that the starting materialN-methoxy-N-methylcinnamoylamide86was transformed absolutely after 24 h in the absence ofany metal catalysts. Additionally, under the optimal reaction conditions, the aminochlorination reactions using 2-NsCl₂87, performed steadily, and the expectingα-chloro-β-amino products were gain edinmoderate to good yields (40-83%) and outstandin gregio selectivities.It is noteworthy to indicated that this method has some benefits like the isolation of the diastereomersproducts88 and 89is totally easy though flash column chromatography and the reaction conditions are compatible at room temperature without using metal catalysts or presence of an inert gasessafeguard.

Scheme 23 Click here to View Scheme

 

Later, Collum and co-workers reported a soft and efficient synthesis of Weinreb enolates91 through coordination between Weinreb amides 90and LDA base in dry THF/benzene mixture solvents³⁷(Scheme 24).Routinely, enolatesform tetramers and dimers represented normally as 93and94, respectively.The generalityremarkable results of this method were produced that the experimental and computationaldata proposed, apparently straightforwardfunction of mutual solvation by THF ligands and the chelating methoxy species. Thecoordination by lithium-build cubic tetramers 93may gain remarkably coordination numbers for further implementations in synthesis92.

Scheme 24 Click here to View Scheme

 

Rueping and co-workers³⁸promotedthe oxidativeal kenylation of aromatic amides, involving Weinreb amides, in presence of[Ru(bpy)₃][PF6]₂ as a catalyst(Scheme 25). The method is remarkable not just for its qualificationand crucialeffective group tolerance, but also actuality it can bewidespread to other amides and a diversity of olefin substrates. The mechanism of such reaction supposed to proceed through primarily with ortho-rhodation of Weinreb amide substrates 95, coordination and insertion of the olefin96, followed by β-hydride elimination step to form the corresponding products97.

Scheme 25 Click here to View Scheme

 

Regarding to the unusual achievement of Weinreb amides asnotableacylating agents in the chemoselectiveomologation reactions with α-substituted methyllithium reagents, Pace et al.³⁹reported a modern route for the isolation and demonstration of tetrahedral intermediates through addition of Lithium carbenoidsto Weinreb amides(Scheme 26). This method suggested to proceed viaaddition ofrobustly nucleophilic organometallic reagents, such as (LiCH₂X and LiCHXY) 99to different substituent of Weinreb amideand N-acylpyrrolessubstrates98through Barbier-type conditions98i, followed by combination with Im-TMS 100(as the trapping agent), then treatment with (NaHCO₃, 5%) and finally purification by Brockmann grade neutral alumina (AloxN-BG3),switching to the corresponding O-trimethylsilyl protected hemiaminal products101.

Scheme 26 Click here to View Scheme

 

While Kapuret al. ⁴⁰reporteda novel usage of palladium-catalyzedorthoC−H halogenation of aromatic substratesincludingsoft-coordinating groups (Scheme 27). Under palladium catalyst cycle and in one-pot usingaprotic solvent, a convenient substrates 103including critical functional groups such as benzoic acid Weinreb amides, anilides, and benzyl nitriles were tolerated and shown an excellent transformation to the corresponding products 104, 105 and 106with higher regioselectivity. Moreover, mechanistic studies output delightful parts with regard to the route of the reaction and the directing group efficiency.

Scheme 27 Click here to View Scheme

 

In 2017, the same group⁴¹reporteda straightforward route for the C-H halogenation process, inclusive iodination, bromination and chlorination of Weinreb amides108, promoted by palladium catalyst (Scheme 28). The successful of this reaction depended on a combination of Pd(OAc)₂and Cu(OTf)₂ with N-halo-succinimide109 (NXS; X = I, Br or Cl) as the halogen source.The reaction is evaluated by its broadaromatic substrates range, bearing electron-withdrawingand -donatinggroupsexclude the nitro groups, which turn off the reaction fromeach of the ortho or para position.

Scheme 28 Click here to View Scheme

 

Next, Wei and co-workers⁴²reported the functional usage of Grignard reagents stimulated the unusual decarboxamidation of α-arylsulfonyl Weinreb Amides(Scheme 29). The mechanistic studies scope displayed that α-sulfo group as electron-withdrawing at the α-position of Weinreb amides111, led to easy functionalize of quaternary carbon and α-quaternary carbon was the crucial component for providing sulfone products 113in moderate to good yields (41-86%). Furthermore, employing excess of Grignard reagent, confirmed the dynamic synthesis of secondary alkyl arylsulfones via C-C bond cleavage reaction pathway.

Scheme 29 Click here to View Scheme

 

In 2018, Joseph and co-workers ⁴³ reported the first novelroute to the synthesisof several symmetrical and dissymmetrical 2,5-cis-disubstituted pyrrolidines by employ the dual reactivity of Weinreb amide species(Scheme 30).The protocol here focused on the cleavage reaction of N-alkoxy-N-methylamidefor desymmetrizing a mesobis-Weinreb amide 115through possible metal-templated arrangement of the two far and quite soft N-methoxy amide functions.On the other hand, the functionalization sequence of 116with methylamine andbenzylamne117awarded a straight entry to pyrrolidine products 118. This method integrated a successive microwave-encouraged tandem double CM/RCDAMfor the preparation of a Weinreb-based pyrrolidine stage to a variety-oriented late-stage functionalization. The authors demonstrated that pattern the steadiness of steric onus of reaction partners, basicity of the organometallic moieties and the liganding potentiality with nitrogen atom of the pyrrolidineisheld to be within the main factors in dominating the reaction selectivity.

Scheme 30 Click here to View Scheme

 

While, Evano and co-workers⁴⁴ detailed simple and largely usefulroute for transformation of imides into scope of, esters124, carboxylic acids 125, amides126, and Weinreb amides127in high yieldsunder mild conditions (Scheme 31). Generally, this reaction proceeded through treatinga range of imides 119having different substitution manners with alcohols120,water 121,amines122, or N,O-dimethylhydroxylamine123,promoted by small amounts of ytterbium(III) triflate as a Lewis acid. The advantages of this reaction are deemed to be inclusive, eco-friendly and mild conditions whichsimplify the one-pot transformation of oxazolidinonederivedimides, versatile intermediates in chemical synthesis.

Scheme 31 Click here to View Scheme

 

Furthermore, Matsunaga group⁴⁵ reportedthe efficient role of (η⁵-entamethylcyclopentadienyl)cobalt(III) catalyst (Cp*Co^III) in the C-H bond functionalization of aromatic,heteroaromatic, and α,β-unsaturated Weinreb amides128(Scheme 32). Generally, several of C-H reactions included allylation, oxidative alkenylation, iodination, and amidation with different reagents such a sallyl carbonate129, ethyl acrylate130, N-iodosuccinimide131, dioxazolones132subsequently were catalyzed by Cp*Co(CO)I₂ in the presence of a cationic silver salt and silver acetate to producerespectivesynthetically valuable building blocks(133-136). Moreover, the mechanistic studies of the C-H allylationrevealed that the C-H activation step was rate determining and practically irreversible.

Scheme 32 Click here to View Scheme

 

Later, Yu and co-workers ⁴⁶providedthe interest of Pd-catalyzed C(sp³)-H arylation protocol, which facilitated by Weinreb amide 137 as a directing group(Scheme 33). The author’s detailed that containment of 3-pyridinesulfonic acid was decisive to such reaction. Furthermore, the computational studies at the DFT level disclosed the importance role of 3-pyridinesulfonic acid for stabilization the cationic palladium catalyst intermediates and accelerate the dissociation of acetate ligands, which led directly cleavage of C(sp³)-H bond of Weinreb Amides.

Scheme 33 Click here to View Scheme

 

Most recently, Erbing and co-workers⁴⁷expanded an Ir(III)-catalyzed C-H ortho-iodination of diverse Weinreb Amides (Scheme 34). The reaction scope included treatment Weinreb Amide substrates 134with N-iodo-succinimide (NIS)135 as a source of halogen in presence of [Cp*Ir(H₂O)₃][SO₄] as the catalyst and trifluoroacetic acid. It is worth that Weinreb amides gave only mono-iodinated products 136in high yield (69-92%), whilst the substratedomain inclusive a wide range of functional groups, substituent’s at ortho position to the directing groupat the beginning limited reactivity, perchance by steric hindrance effect.

Scheme 34 Click here to View Scheme

 

Conclusion

More recently, diverse studies have detailed the use of Weinreb amide constructions as delightful substrates in organic synthesis reactions. In this review, we highlighted this part of the literature, containing unusual development synthesis of Weinreb amides and their applications with clarify protocol examples of these processes. Furthermore, this paper contains the ultimate conclusions of the researchers and usefully furnishes reaction information for the most important reaction and many references to the native literature.

Acknowlegement

We acknowledge the University of Zakho, Faculty of Science, and Department of Chemistry for providing all the facilities.

References

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