Acyclic amides

Whereas cyclic allyhc alcohols of normal size can only yield (Z)acyclic allylic alcohols preferentially give ( )-isomers. Indeed, the Meerwein-Eschenmoser-Claisen rearrangement is an excellent method for the stereoselective formation of di- and trisubstituted (E)-double bonds in acyclic systems. The high diastereoselectivities observed (dr >95 5) can be explained by invoking a chair shaped transition state 35a or 36a (Scheme 7.15). This minimizes... 

Heterocyclic compounds carrying potential hydroxyl groups are cyclic amides or vinylogs of amides. There is much physical evidence that acyclic amides exist almost entirely in the oxo form (for references see reference 6), and the apparent contradiction that ultraviolet spectral data appeared to favor the imidol formulation has now been explained on steric grounds. The value of pKr is estimated to be about 7 on the basis of pK measurements for acyclic amides. Extensive evidence, summarized in the following sections, shows that for a- and y-hydroxy heterocyclic compounds, the cyclic amide form usually predominates by a substantial factor, often ca. 10 . 

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

The conversion of a 4-arylazo-5-oxazolone into a 1,2,4-triazole by reaction with a Grignard reagent is mentioned in Section II, B, 3. In HiTnilar fashion, the rearrangement of compound 30 to derivatives of 3-carboxy-l,5-diphenyl-lfl -l,2,4-triazoles (40) proceeds readily in the presence of strong nucleophiles [Eq. (26)]. This transformation undoubtedly occurs by ring opening and dehydrative cychzation, and, indeed, the acyclic amide and hydrazide 41 have been isolated. ... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

The reaction is effective with both acyclic and cyclic amides., or lactams, and is a good method for preparing cyclic amines. 

Most heterocycles have the same chemistry as their open-chain counterparts. Lactones and acyclic esters behave similarly, lactams and acyclic amides behave similarly, and cyclic and acyclic ethers behave similarly. In certain cases, however, particularly when the ring is unsat lira ted, heterocycles have unique and interesting properties. 

An alternative method for the preparation of AL(l-alkoxylalkyl)amides is the sodium borohy-dride reduction of A -acylimidates. Acyclic A-acylimidates are conveniently obtained by reaction of an acid chloride with an imidate47 in the presence of triethylamine. For acid-labile carboxylic acids a mild one-pot procedure has been developed48. 

Another occasionally used method for the preparation of acyclic A-(l-alkoxyalkyl)amides (or carbamates) proceeds via addition of reactive carboxylic acid derivatives to aldimines. In a one-pot procedure, treatment of the imine with the acid chloride (or ethyl chloroformate) and subsequent (m)ethanolysisofthe intermediary a-chloroamide leads to the oc-alkoxyamide56-58. 

The electrochemical oxidation of cyclic and acyclic, V-monosubstitilted and ATY-disubstituted amides and carbamates in a nucleophilic solvent, known as the Ross-Eberson-Ny berg reaction, is a synthetically very useful, clean and efficient method for the introduction of a-oxygen substituents under mild reaction conditions6 1 0. 

Chromium aminocarbenes [39] are readily available from the reaction of K2Cr(CO)5 with iminium chlorides [40] or amides and trimethylsilyl chloride [41]. Those from formamides (H on carbene carbon) readily underwent photoreaction with a variety of imines to produce /J-lactams, while those having R-groups (e.g.,Me) on the carbene carbon produced little or no /J-lactam products [13]. The dibenzylaminocarbene complex underwent reaction with high diastereoselectivity (Table 4). As previously observed, cyclic, optically active imines produced /J-lactams with high enantioselectivity, while acyclic, optically active imines induced little asymmetry. An intramolecular version produced an unusual anti-Bredt lactam rather than the expected /J-lactam (Eq. 8) [44]. 

Nearly all of the polymers produced by step-growth polymerization contain heteroatoms and/or aromatic rings in the backbone. One exception is polymers produced from acyclic diene metathesis (ADMET) polymerization.22 Hydrocarbon polymers with carbon-carbon double bonds are readily produced using ADMET polymerization techniques. Polyesters, polycarbonates, polyamides, and polyurethanes can be produced from aliphatic monomers with appropriate functional groups (Fig. 1.1). In these aliphatic polymers, the concentration of the linking groups (ester, carbonate, amide, or urethane) in the backbone greatly influences the physical properties. 

Imides can be prepared by the attack of amides or their salts on acyl halides, anhydrides, and carboxylic acids or esters. The best synthetic method for the preparation of acyclic imides is the reaction between an amide and an anhydride at 100°C catalyzed by H2S04. When acyl chlorides are treated with amides in a2 l molar ratio at low temperatures in the presence of pyridine, the products are N,N-diacylamides, (RCO)3N. ... 

A series of chiral phosphinous amides bearing pendant oxazoline rings (50, Ri=H,Tr R2=H,Tr, 51, Ri=H,Tr R2=H,Tr and 54, Ri=H,Tr R2=H,Tr in Scheme 41) have been used as ligands in the copper-catalyzed 1,4-addition of diethylzinc to enones. Two model substrates have been investigated, the cyclic 2-cyclohexenone and the acyclic trans-chalcone. The addition products are obtained quantitatively in up to 67% ee [171]. 

A. From Amides and Phosphorus(v) Halides.—The Kirsanov reaction remains one of the most important routes to acyclic phosphazenes some recent examples of this reaction are summarized below ... 

It has been found that a number of bidentate ligands greatly expand the scope of copper catalysis. Copper(I) iodide used in conjunction with a chelating diamine is a good catalyst for amidation of aryl bromides. Of several diamines that were examined, rra s-yV,yV -dimethylcyclohexane-l,2-diamine was among the best. These conditions are applicable to aryl bromides and iodides with either ERG or EWG substituents, as well as to relatively hindered halides. The nucleophiles that are reactive under these conditions include acyclic and cyclic amides.149... 

Similarly, acyclic co-olefmic N-tosyl amides with vinyl bromides have also been used to give pyrrolidones and piperidones in 49 to 82 % yield (eight examples) [54]. 

Amides of phosphorous acid (e.g., P(NMe2)3 and the bicyclic compound (L16)) are useful ligands for cross-coupling of arylboronic acids with aryl bromides and chlorides (system Pd(OAc)2/2L, Cs2C03, toluene, 80 °C), the bicyclic amide being markedly more effective than simple acyclic ones.421 Amides of phosphinous acids are also excellent bidentate ligands with PN coordination mode ((L6), Section 9.6.3.4.2). 

The intermolecular coupling of lactams and acyclic amides has also been reported. Reactions of carbamates with aryl halides occurred in the presence of catalysts ligated by P(/-Bu)3.78 Both carbamates and amides coupled with aryl halides in the presence of a catalyst bearing Xantphos.90 In addition, the coupling of lactams with aryl halides has been successful. A combination of Pd(OAc)2 and DPPF first formed A-aryl lactams in good yields from 7-lactams, but the arylation of amides was improved significantly by the use of Xantphos (Equations (20) and (21)).90 91 The reaction of aryl halides with vinyligous amides has also been reported 92... 

In all cases, the high degree of pyramidality attributed to the presence of two electronegative oxygen atoms at nitrogen, confirms the predictions of HF/6-31G calculations.5 On the basis of geometries for all acyclic amides in the Cambridge Structural Database in 2002,117 amides 31b and 31f are the most pyramidal amides of this type.5... 

Davis et al.111 developed another method for reagent-controlled asymmetric oxidation of enolates to a-hydroxy carbonyl compounds using (+)-camphor-sulfonyl oxaziridine (147) as the oxidant. This method afforded synthetically useful ee (60-95%) for most carbonyl compounds such as acyclic keto esters, amides, and a-oxo ester enolates (Table 4-20). 

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