Imines reaction with ketene complexes

The chiral-modified binaphthol complex (23) has been prepared (Eq. 10) and shown to be an efficient catalyst for enantioselective Memnich-type reactions [9]. The reaction of imine (24) with ketene silyl acetal in the presence of the catalyst 23 with NMI afforded /3-amino acid derivatives 25 and 26 in high enantioselectivity (Eq. 11). 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

In the first step, catalyst 64c attacks ketene 66 to form a zwitterionic enolate 71, followed by Mannich-type reaction with imine 76 (Fig. 40). A subsequent intramolecular acylation expels the catalyst under formation of the four-membered ring. Utilizing 10 mol% of 64c, N-Ts substituted (3-lactams 77 were prepared from symmetrically as well as unsymmetrically substituted ketenes 66, mainly, but not exclusively, with nonenolizable imines 76 as reaction partners [96]. Diastereos-electivities ranged from 8 1 to 15 1, yields from 76 to 97%, and enantioselectivities from 81 to 94% ee in the case of aliphatic ketenes 66 or 89 to 98% ee for ketenes bearing an aromatic substituent. Applying complexes 65 or the more bulky and less electron-rich 64b, ee values below 5% were obtained. 

More recently, we have found that the role of the isomerization pathways in the reaction between ketenes and imines can be extended to the (E)/(Z) isomerization of imines themselves [68]. Thus, the stereocontrol observed in the reaction between methoxyketene 41 and (E)-imines (62a,b) was attributed to the competition between the energy barriers associated with the formation of intermediates (63a,b) and (65a,b) and the energies of activation corresponding to the isomerisation of (E)-imines (62a,b). Inclusion of isomerisation processes involving both imines (62a,b) and zwitterionic intermediates (63a,b) and (65a,b) led to a more complex kinetic analysis. As the final steps leading to (3-lactams (64) can be considered irreversible, the formation of both cis- and trans-(64) can be described by (3) and (4) ... 

Hegedus et al. discovered that irradiation of chromium-carbene complexes resulted in a photoinsertion of CO into the Cr-carbene bond to form Cr-ketene complexes [96, 97]. This opened novel routes to the preparation of valuable compounds via Cr-ketene chemistry. Among them, the reaction of metallated ketenes with imines was intensively explored [98-100]. Within this context, the reaction between several model Cr-ketenes (120) and imines was explored at the B3LYP/6-31G ECP level of theory [101, 102], The mechanisms thus obtained are reported in Scheme 31. 

Nowadays, it is an accepted mechanistic model [5, 6] that the photolysis step (which proceeds under thermo-reversible CO insertion) leads to species best described as chromium ketene complexes of type 7 (Scheme 2). Indeed, these intermediates exhibit a ketene-like reactivity they undergo [2 + 2] cycloaddition reactions with olefins, imines and enol ethers, whereas reaction with nucleophiles leads to carboxylic acid derivatives. 

Enantiomerically enriched or pure benzaldehydeimine complexes react with nucleophiles such as Grignard see Grignard Reagents) and organozinc reagents, and they participate in a number of cycloaddition reactions. Enantiopure tricyclic /3-lactams can be obtained from stereoselective [2 - - 2]cycloaddition between a complexed chiral benzaldehyde imine and a ketene (Scheme 85). For example, reaction of (44) with acetoxyketene gives (45). 

A new synthetic route to j8-lactams has recently been reported " involving the photolytic reaction of chromium carbene complexes with imines. Detailed analysis now establishesa mechanism involving the initial photolytic formation of a ketene complex (24). This is followed by nucleophilic attack by the imine at the ketene carbonyl to produce a zwitterion intermediate, which undergoes a conrotatory ring closure to form the j8-lactam as shown in Scheme 15,... 

The synthesis of monocyclic 3-amino-P-lactams by the photolytic reaction of imines with pentacarbonyl[(dibenzylamino)carbene]chromium(0) was developed by Hegedus and co-workers [74]. These reactions are closely related to the previously described [2 -h 2]-cycloaddition reactions in that they are thought to involve attack of the imine nitrogen on a photogenerated, metal-bound ketene, followed by ring closure (Scheme 15). In a synthesis of a nocardicin precursor, optically active imine trimer 122 was photolyzed with carbene complex 123 providing a 46% yield of a 1 1 diastereomeric mixture of lactams... 

While no asymmetric induction was observed in the present instance, prior examples with more sterically biased imines had given high levels of induction. A solution to this problem for the monocyclic p-lactam case was provided by chiral carbene complex 125 [75]. A variety of other imine analogs with N-heteroatom bonds were examined in the reaction sequence without success, presumably due to insufficient nucleophilicity of the nitrogen atom for attack on the ketene complex or insufficient electrophilicity of the imine analog for the required ring closure. 

A miscellany of papers dealing with the potency of the thioureido neighbouring group in nucleophilic substitution processes, the complexing ability of thioureas towards macrocyclic polyethers, and the cycloaddition reactions of thiocarbamoyl isothiocyanates (190) with ketens, ketenimines, imines, isocyanates, carbodi-imides, and isonitriles also deserve attention. 

The stereoselectivity of the reaction of ketenes with imines to produce -lactams depends upon the method of ketene generation and different results are obtained in reactions involving acid chloride/NEt versus the photolysis of chromium carbene complexes. ) The complex Cr sC(CH2)2CHMeO (CO)s and aliphatic aldehydes RiR CHCHO bearing a-hydrogen atoms, in... 

A comparison of the reaction products obtained from RCH=NPh (R = MeO, Ph, PhCH=CH) and two heterocyclic imines with ketenes, generated by photolysis of oxazolidine- and oxazolidinone-chromium carbene complexes and from the oxazolidi-none carboxylic acid chlorides, indicated high yields and high diastereoselectivities in some of these reactions... 

Although the photodriven reactions of chromium carbene complexes with imines superficially resemble those of free ketenes, there are major differences. The optically active oxazolidine carbene (Table 5) gave excellent yields and high ee values when allowed to react with imidates, oxazines, thiazines, and... 

In an analogous late-stage arylation approach, terminal alkyne 31 was envisioned as a versatile intermediate. Slow addition of 4-pentynoyl chloride to imine 3 and (n-Bu)3N at reflux (efficient condenser, 100°C, 12 h, 1 1 toluene heptane) afforded only trace amounts of 31. Reaction of 4-pentynoyl chloride with triethylamine in methylene chloride under preformed ketene conditions ( 78°C, 1 h), followed by addition of 3 and warming to — 10°C over 4 h, afforded a complex mixture of products. Since high-yield preparation of 31 remained elusive, access to internal alkynyl analogs (type 33) was accomplished by preassembly of the appropriate arylalkynyl acid substrate for the ketene-imine cycloaddition reaction (Scheme 13.9). 

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

If the metal-binaphthyl complex is not fitted directly into the cyclic transition state, it becomes difficult to explain the asymmetric inductions observed. The following rule seems to be generally valid for both BINOL and BINAP complexes The complexation of carbonyl or imine moieties by (R)-binaphthyl-metal complexes results in a shielding of the si face, the reaction proceeds from the re face. Correspondingly, the opposite principle applies when (STbinaphthyl complexes are used. All aldol reactions and carbonyl-ene reactions which are catalyzed by binaphthyl complexes abide by this rule [18], and the scheme can also be applied to the addition of ketene-silyl-acetals to imines with boron-BINOL catalysts [19]. 

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