Carbonyl activation modes

The lactone concept is not restricted to the simple model biaryl synthesis presented here. It has been successfully expanded to a broad series of structurally diverse biaryl substrates (e.g., lactones with additional stereocenters and functional groups, configurationally stable lactones, seven-membered lactones, and again configurationally unstable biaryl hydroxy aldehydes ), to different activation modes in the ring-opening step (e.g., use of metallated nucleophiles, carbonyl activation by Lewis acids, (Ti -complexation, etc.), and for various strategies of stereoselection (e.g., external vs. internal asymmetric induction). ... 

Scheme 3.1 Three modes of carbonyl activation toward nucleophilic attack.

The intensities of the infrared-active carbonyl stretching mode of the hexacarbonyl cations [Mn(CO)6] and [Re(CO)6] + have been measured (77). The absolute intensities of the hexacarbonyl cations are in the order [M(CO)6]+ < M(CO)6 < [M(CO)6]-, which corresponds to the reduction of 77-back-bonding from metal to carbonyl as the positive charge on the metal is increased. (34)... 

The geometry of the tricarbonyl cations [Co(CO)3L2]+ has been established, from the infrared-active carbonyl stretching modes [L = PPh3 (240)] and the proton NMR [L = Tdp (158)], to be trigonal bipyramidal with the phosphines disposed trans in the axial positions. 

Photochemical activation of transition metal carbonyls has been used as a preparative tool for substitution of carbonyl ligands by donor molecules or unsaturated hydrocarbons for many years (7-6). The advantage of photochemical activation in comparison with thermal activation is the possibility of conducting reactions at fairly low temperatures. Hence even thermolabile products can be prepared and isolated by appropriate treatment of the reaction mixtures. However, due to the various activation modes of transition metal carbonyls by UV light, often more than one product is obtained, and chromatographic separation is necessary. Limitations are set primarily by the amount of substance which can be irradiated in solution at one time. 

It appears that the relative intensity of the two Raman-active modes for octahedral carbonyl species show a similar dependence on the formal oxidation state of the central metal [S. F. A. Kettle, I. Paul, and P. J. Stamper, Chem. Commun. 1724 (1970)]. 

I n 1993, the first cinchona-catalyzed enantioselective Mukaiyama-type aldol reaction of benzaldehyde with the silyl enol ether 2 of 2-methyl-l -tetralone derivatives was achieved by Shioiri and coworkers by using N-benzylcinchomnium fluoride (1, 12 mol%) [2]. However, the observed ee values and diastereoselectivities were low to moderate (66-72% for erythro-3 and 13-30% ee for threo-3) (Scheme 8.1). The observed chiral inductioncan be explained by the dual activation mode ofthe catalyst, that is, the fluoride anion acts as a nucleophilic activator of the silyl enol ethers and the chiral ammonium cation activates the carbonyl group of benzaldehyde. Further investigations on the Mukaiyama-type aldol reaction with the same catalyst were tried later by the same [ 3 ] and another research group [4], but in all cases the enantioselectivities were too low for synthetic applications. 

In 1994, the first enantioselective trifluoromethylation reaction was achieved with the Ruppert-Prakash reagent, TMSCF3, in the presence of the cinchona-based quaternary ammonium fluoride 140 [65]. The chiral induction can arise from the dual activation mode of the catalyst, that is, the fluoride anion acts as the nucleophilic activator of (TMS)CF3 and the chiral ammonium cation activates the carbonyl group of 141. However, the observed ee values of the obtained carbinols 142 do not exceed 51 % and decrease considerably when nonaromatic carbonyl compounds (15% ee for R1 = n-C7H15 R2 = H) are used, which implies that 7t-7t stacking interactions between the carbonyl compound and cinchoninium occur (Scheme 8.54). 

Figure 11.1 Asymmetric activation modes of carbonyl compounds.

Rueping M, Kuenkel A, Atodiresei I (2011) Chiral Br0nsted Acids in Enantioselective Carbonyl Activations - Activation Modes and Applications. Chem Soc Rev 40 4539... 

Table 5.6. Infrared and Raman active carbonyl stretching modes for octahedral complexes M(CO) L, ...

A dual activation mode based on a network of hydrogen bond interactions is assumed being active in all these methodologies. In particular, the C6 —OH group could activate the carbonyl derivatives, while the quinuclidine tertiary nitrogen atom could modulate the reactivity of the hydroxybenzene (the case of Cinchona alkaloids is reported in Fig. 5.3). 

CARS microscopy derives its analytical capability from the Raman active modes of molecules [75]. There are two specific vibrational modes in the Raman spectra of acrylic based polymers that can give insights on the polymerization process and the structural integrity of microstructures fabricated via TPP. One is around 3000 cm and arises from the stretching of both aliphatic and aromatic carbon-hydrogen bonds. The other one is around 1640 cm and is due to the carbon-carbon double bond resonant vibration with the carbonyl group present in the acrylic units of the starting materials [73, 76]. 

During our recent study on utilizing tropone as diene for platencin synthesis [52], many other types of Lewis acid catalysts including the above mentioned oxazaborolidine catalysts all failed to promote the desired inverse-electron-demand Diels-Alder reaction. Fortunately, the dinucleus BINOL-aluminum catalysts were found to give very nice yields and enantioselectivities (Fig. 11) [53]. Activation mode in this reaction can be either intramolecular LLA assembly or double aluminum coordination to carbonyl substrate. Future research efforts are directed toward more applications with this type of catalyst, and more detailed understanding of the nature of this type of catalysts. 

The use of chiral primary or secondary amines as covalent catalysts allows for the activation of carbonyl componnds for different reactions. Either the initially formed imininm species are the reactive intermediate (LUMO lowering), which is mainly the case when using a,p-unsatnrated carbonyl compounds, or the derived enamine can be ntilized for enolate-type reactions (HOMO activation), or, after a single electron oxidation of the enamine, a singly occnpied molecular orbital (SOMO) activation is possible (Scheme 6.18) [14, 31, 32], In addition, by combining these complementary activation modes, it has been possible to carry out organocascade reactions with excellent control of... 

The dual activation mode of the aforementioned cinchona alkaloid-derived thiourea catalysts proved to be highly effective in catalyzing the asynunetric Mannich reaction, among other transformations. These findings prompted the development of new, more simple bifunctional chiral catalysts that are predominately based on tra 5 -l,2-diaminocy-clohexane. For example, the application of the thiourea catalyst 120, which was developed by Takemoto and coworkers, afforded upon the reaction of Af-Boc-protected imines with diethyl malonate the desired chiral amines in good chemical yields (up to 91%) and enantioselectivities (98% ee) (Scheme 11.23) [81]. The catalytic mechanism presumably involves deprotonation and coordination of the active carbonyl compound by the chiral tertiary amine moiety. The formed enolate then attacks the si-face of the... 

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