Amination enolates

There are a few published reports on the use of HOSA 3p for enolate amination. Some /3-diketo compounds were reacted with HOSA in 10% aqueous K2CO3 solution at room temperature to give substituted pyrroles (equation 21) ° °. ... 

The Tsuji-Trost Reaction (or Trost Allylation) is the palladium-catalyzed allylation of nucleophiles such as active methylenes, enolates, amines and phenols with allylic compounds such as allyl acetates and allyl bromides. 

Diastereoselective enolate amination as an approach to a-aminoke-tones.42 We have demonstrated that the Mannich reaction is successful for the highly stereoselective introduction of P-aminoketone moieties (vide supra, Asymmetric Mannich Reactions24). The diastereofacially selective electrophilic amination of enolates is attractive as a complementary approach to the asymmetric... 

Enolate > amine > azo compounds > ring N > carboxylate > ether > carbonyl... 

Enolate Amination. Amination likewise can be effected using Di-t-butyl Azodicarboxylate (DBAD). Despite the excellent yields and diastereoselectivity obtained using this methodology (eq 24), the harsh conditions required for further transformation of the resultant hy drazide adducts (Triftuoroacetic Acid and hydrogenation at 500 psi over Raney Nickel catalyst) limit its synthetic utility. 

Enol Amination. The Cu[(S,5)-t-Bu-box] (OTf)2 complex was found to be optimal for promoting the enantioselective conjugated addition of enolsilanes to azodicarboxylate derivatives (eq 13). This methodology provides an enantioselective catalytic route to differentially protected ot-hydrazino carbonyl compounds. Isomerically pure enolsilanes of aryl ketones, acylpyrroles, and thioesters add to the azo-imide in greater than 95% ee. The use of an alcohol additive was critical to achieve catalyst turnover. Amination of cyclic enolsilanes was also possible. For example, the enolsilane of 2-methylindanone provides the adduct containing a tetrasubstituted stereogenic center in 96% ee and high yield. Acyclic (Z)-enolsilanes react in the presence of a protic additive with enantioselection up to 99%. ... 

Theoretical Study of the Intramolecular Proton Transfer in Lithium-Enolate Amine Complexes. ... 

Barton and co-workers have investigated the use of triarylbismuth dihalides and related compounds for synthetic purposes. These compounds can be used for the oxidation or arylation of a variety of alcohols, enols, amines, phenols, thiols, hydrazine, nitroalkanes and others (Sections 5.2.4, 5.4.3 and 5.5.2). 

Tetraphenylbismuth(V) compounds have been used as the oxidizing agents for alcohols under basic conditions (Section 5.2.4). They are also employed as the phenylating agent of alcohols, enols, amines, phenols, indoles, thiols, sulfinates, nitroalkanes, and others (Section 5.5.2). The selectivity between O- and C-arylations is dependent on the reaction conditions employed 2-naphthol is O-phenylated by tetraphenylbismuthonium trifluoroacetate under acidic conditions, whereas it is C-phenylated under basic conditions. 

Very often lithium enolates, e.g., those produced with lithium diisopropylamide, yield only low levels of deuterated carbonyl compounds when treated with deuterium oxide or deuterated alcohols (see table below). This is due to the fact that the secondary amine formed becomes involved in the protonation162. Deuterated acids, e.g., diisopropyl (2/ ,3/ )-2,3-dihydroxy-<72-butanedioate behave in a similar way, however, the observed enantioselectivities are somewhat higher. The complex from which a deuteron (or proton) is transferred probably contains lithium enolate, amine and the proton source (see also Section 2.1.6.1.2.). 

Enantiomerically pure oxazolines and oxazolidinones have found widespread application in organic synthesis as chiral auxiliaries. They have been mainly used for the synthesis of enantiomerically pure amino acids but also as chiral auxiliaries to produce non-racemic enolates as pioneered by Evans.The reaction types proceeding with high stereocontrol include enolate alkylation, enolate oxidation, enolate halogenation, enolate amination, enolate acylation, aldol reaction and Diels-Alder reactions. 

Phenols, enols, amines, aldehydes, and ketones interfere with this test. 

Activation of dimethyl sulfoxide by oxalyl chloride, as developed by Swern and co-workers [1317-1319,1335,1371-1373], has become the most used of these oxidation procedures, but several of the other methods are also convenient and effi-dent. The usual nudeophiles have been alcohols, phenols, enols, amines, and oximes. 

Ireland s explanation for the HMPA effect has been challenged by the assumption that, under these conditions, thermodynamic control occurs in enolate formation cf. Ref. [58]. This criticism was not substantiated, as outlined in the relevant discussion in Ref. [2cj see also Refs. [39,45]. Guided by cr) tal structures of mixed enolate-amine gregates, a rationale for cjs/tr s-selectivity in formation of ester and ketone enolates was proposed based on steric effects see Ref. [12]. 

Scheme 4.100 Evans azidation of W-acyl oxazolidinones 468 and 474 via the potassium enolates. Cleavage of the auxiliary and application of enolate amination for a synthesis of tripeptide OF-4949-III (476).

Oppolzer s camphor-based sultams 92 proved itself as an efficient, robust auxiliary for enolate amination with 1-chloro-l-nitroso cyclohexane 486 as an electrophile. Thus, sultams 92 were first deprotonated with NaHMDS, and to the sodium enolates thus formed was added a solution of the blue nitrosochloride 486. Decolorization occurred immediately, and the mixture was quenched with hydrochloric acid to give hydroxylamines 487, in all cases as essentially pure diastereomers. The reductive cleavage of the nitrogen-oxygen bond was achieved with zinc dust to yield a-aminoacyl sultams 488. By mild hydrolysis with lithium hydroxide, the chiral auxiliary 91 was removed and recovered under concomitant formation of a-amino acids 490. Any racemization was avoided by applying this procedure, even in the case of the labile substrates with R equals a phenyl or / r -methoxyphenyl substituent. On the other hand, the auxiliary could be cleaved at the stage of hydroxylamines 487, so that not only a-amino acids 490 but also a-hydroxyamino acids 489 became available with excellent enantiomeric purity (Scheme 4.103) [232]. 

Scheme 5.131 Enantioselective silver-catalyzed enolate amination with azodicarboxylate 535.

Despite the elegancy of the approaches toward a catalytic enantioselective enolate amination, one has to be aware that a certain restriction is evident from the substitution pattern at the nitrogen in the amination products that seems to be rather special than general. Another challenging problem among the oxidative transformations of enolates is the catalytic enantioselective halogenation. Efforts... 

Evans has pioneered the use of carboximide-derived enolates in diastereo-selective enolate alkylation reactions [15, 82]. As discussed in subsequent chapters, N-acyl oxazolidinones (such as 114, 115, and 116) enjoy a unique position in asymmetric synthesis as chiral auxiliaries with wide applications in numerous mechanistically unrelated asymmetric transformations, among them aldol (Chapter 4), Diels-Alder (Chapter 17), enolate amination (Chapter 10), and conjugate addition (Chapter 12) reactions. Oxazolidinones 114 and 115 generally lead to Ca-substituted carboximide products in one dia-stereomeric series (cf 119, dr>99 1), while the complementary diastereo-meric adducts such as 122 dr =98 2) can be accessed through the use of oxazolidinone 116 (Scheme 3.18) [82]. 

A different strategy devised by Evans prescribes the reaction of acyloxazo-lidinone-derived enolates (cf 98) with trisyl azide (99) to give the -substi-tuted azides such as 100 (Scheme 10.16) [82]. This electrophilic enolate amination process was highlighted in the synthesis of cyclic peptide K-13 (101), an inhibitor of angiotensin-converting enzyme [83], As an aside, another remarkable feature of this synthetic endeavor is the chemoselectivity displayed in the enolization of imide ester 98 in the presence of the methyl ester. 

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