Enamine, chelated

At 25°C, the keto-B-oxazoline (from VIII) and keto-B-thia-zoline (from IX) are nearly exclusively (>90 %) in the chelated enamine form both for model compounds and copolymers,either in bulk or in most solvents over a wide range of polarity (from CHCl to DMSO). The keto form does appear only in very strong hydrogen bonding donor solvents like trifluoroethanol (TFE). 

The orf/io-methoxy group of 2-(o-methoxyphenyl)oxazolines has been displaced with organometallic reagents in a similar fashion (75JA7383). The excellent activating effect of the oxazoline combined with its ability to form a chelated enamine-like intermediate on addition of the organometallic is responsible for the success of this process. 

Stork and coworkers48 have shown that the deprotonation of chelating enamines yields / - rather than a-lithium enamines (equation 26). 

Keywords chelates, enamines, hypervalent compounds, schifT bases, silicon... 

In an aliphatic system. Stork has reported the regioselective lithiation of chelating enamines such as (9), to give vinyl carbanions such as (10 Scheme 6). Woik-up often results in hydrolysis of the enamine, and in die case of addition to aldehydes, dehydration. ... 

Enantioselective alkylation of cyclohexanones can be accomplished via a chiral lithio-chelated enamine.30... 

Deprotonation of the chelating enamine derived from cyclohexanone and N,N,N -trimethylethylenediamine led to complete formation of the vinyl carbanion, rather than the expected allyl... 

The metal chelating 2,2"-bipyridines, useful in material science, can be obtained by this method.For example, bis-triazines 92, in the presence of two equivalents of enamine 67, will produce bipyridines 93. 

The use of hydrazone or enamine derivatives of ketones or aldehydes offers the advantage of stcreocontrol via chelated azaenolates. Extremely useful synthetic methodology, with consistently high anti selectivity, has been developed using azaenolates based on (S)- or (R)-l-amino-2-(methoxymethyl)pyrrolidine (SAMP or RAMP)51 58 (Enders method, see Section 1.5.2.4.2.2.3.). An example which illustrates the efficiency of this type of Michael addition is the addition of the lithium azaenolate of (5 )-l-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazone of propanal (R = II) to methyl (E )-2-butenoate to give the nub-isomer (an 1 adduct) in 80% yield with a diastereomeric ratio > 98 2,... 

Two closely related methods for the diastereoselective preparation of <5-oxo esters have been developed. The first method uses the chelated lithio enamine 2. These Michael donors are readily available from the tert-butyl ester of L-valine and jS-oxo esters. The Michael addition of this lithio enamine 2 to 2-(arylmethylene)propanedioates, followed by hydrolytic removal of the auxiliary, provides d-oxo esters with contiguous quaternary and tertiary carbon centers with high diastereoselectivity59 60. 

Oxo esters are accessible via the diastereoselective 1,4-addition of chiral lithium enamine 11 as Michael donor. The terr-butyl ester of L-valine reacts with a / -oxo ester to form a chiral enamine which on deprotonation with lithium diisopropylamide results in the highly chelated enolate 11. Subsequent 1,4-addition to 2-(arylmethylene) or 2-alkylidene-l,3-propanedioates at — 78 °C, followed by removal of the auxiliary by hydrolysis and decarboxylation of the Michael adducts, affords optically active -substituted <5-oxo esters232 (for a related synthesis of 1,5-diesters, see Section 1.5.2.4.2.2.1.). In the same manner, <5-oxo esters with contiguous quaternary and tertiary carbon centers with virtually complete induced (> 99%) and excellent simple diastereoselectivities (d.r. 93 7 to 99.5 0.5) may be obtained 233 234. 

Comparison of their rate of onset and recovery of a treated mucosa has been made [37]. Fatty acids have strong and fast reactivity and allow for a fast recovery of the barrier function. Bile salts and salicylates are moderate, fast-acting agents with fast barrier-function recovery. Strong surfactants and chelators have strong or moderate reactivity and a slow recovery of barrier function. Solvents like dimethylsulfoxide and ethanol have moderate reactivity and act primarily as agents to improve drug miscibility in an aqueous environment. The enhancers listed above are also effective in the small intestine [22]. Enhancers that are more colon specific include ethylaceto-acetate, which must be first metabolically transformed to enamine [38]. 

Chelating agents such as EDTA, EGTA, citric acid, phytic acid and enamine derivatives Ethanol, DMSO, DMF, and DMAC... 

Simple alkylation of the chiral chelate complex leads to formation of chiral dialkylacetic acids (Scheme 109).3S5 388 Simpler chiral enamines can also be used. The formation of chiral propanoic acids results from a resolution of racemic alkyl halides by the interaction of a chiral lithiooxazoline, which recognizes and reacts with one enantiomer at the expense of the other (Scheme 110).389 The above aspects of the asymmetric carbon—carbon bond formation from chiral oxazolines have been reviewed by Meyers.390... 

The scope and mechanism of ionic hydrogenation of iminium cations have been investigated for a CpRuH catalyst bearing a chelating diphosphine.64 The mechanism involves three steps hydride transfer (from the catalyst) to form an amine, coordination of H2 to the resulting ruthenium cation, followed by proton transfer from the dicoordinated H2 to the amine. The cationic intermediate [e.g. CpRu(dppm)( 72-H2)+] can be used to hydrogenate enamines provided that the latter are more basic than the product amine. The relative reactivity of C=C and C=N bonds in a, ft -unsaturated iminium cations has also been investigated. 

The enamine in 9.31 can coordinate to the metal center in three different ways. It can act as a monodentate ligand by coordinating either through the N atom lone pair or the double bond. It can also act as a chelating ligand. As we will see, the proposed catalytic intermediates in the catalytic cycle have all three different types of coordination. 

A simplified proposed catalytic cycle is shown in Fig. 9.6. The precatalyst, an analogue of 9.14 with S-BINAP, undergoes reaction 9.3 to generate 9.32, where the enamine acts as a chelating ligand. Note that in 9.32 asymmetric isomerization has already taken place. How this may come about will be dis-... 

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