Carbonyl compounds, a-alkoxy

Addition to a-Hydroxy or a-Alkoxy Carbonyl Compounds Chelation-Controlled 1,2-Asymmetric Induction... 

SCHEME 8. Schematic representation for the chelate-controlled addition of an organometaUic reagent (M—R) to the carbonyl group of a chiral a-alkoxy carbonyl compound (17). Two diastere-omers 18 with different orientation of R with respect to CH2R can be obtained. The syn diastereomer is obtained when the nucleophihc attack of R takes place on the same face of the plane, defined by the carbonyl group and the R-substituted carbon atom, where CH2R is located in the chelate complex... 

The addition paths of two separated MeMgCl molecules to the carbonyl group of chiral a-alkoxy carbonyl compounds, which are shown in Schemes 8 and 9 and in Figure 11 in Section IV, were traced. However, in these models, one MeMgCl molecule bridges two oxygen atoms and acts merely as a catalyst. Instead, the Schlenck dimer (MeMgCl)2 should be considered for the carbonyl reactant coordination. 

Br, or I) (equation 1). Another method relies on alkylation of a-hydroxy or a-alkoxy carbonyl compounds. The induction of diastereoselectivty, in these cases, is achieved through the use of chiral auxiliaries and other stereodirecting groups (equation 2). The third method frequently utilizes the nucleophilic addition of hydride or other carbanions to a-dicarbonyl compounds (equation 3). In addition to being laborious, nonoxidative methods are limited to the synthesis of acyclic compounds, which greatly reduces the magnitude of their synthetic practicality. 

Most examples of [1,2]-Wittig rearrangements involve relatively basic carbanions. However, a few reports have demonstrated that enolates derived from a-alkoxy carbonyl compounds can also participate in [1,2]-Wittig rearrangements. For example, a-benzyloxy lactam 34 was converted to 35 in 63% yield upon treatment with LiHMDS. Related enolate Wittig rearrangements have also been used in tandem processes as described below. 

V. Jonas, G. Frenking, and M. T. Reetz, OrganometalUcs, 14, 5316 (1995). Mechanism of the Chelation Controlled Addition of CH3TiCl3 to a-Alkoxy Carbonyl Compounds. A Theoretical Study. 

I-Oialkoxy carbonyl compounds are a special class of chiral alkoxy carbonyl compounds because they combine the structural features, and, therefore, also the stereochemical behavior, of 7-alkoxy and /i-alkoxy carbonyl compounds. Prediction of the stereochemical outcome of nucleophilic additions to these substrates is very difficult and often impossible. As exemplified with isopropylidene glyceraldehyde (Table 15), one of the most widely investigated a,/J-di-alkoxy carbonyl compoundsI0S, the predominant formation of the syn-diastereomer 2 may be attributed to the formation of the a-chelate 1 A. The opposite stereochemistry can be rationalized by assuming the Felkin-Anh-type transition state IB. Formation of the /(-chelate 1C, which stabilizes the Felkin-Anh transition state, also leads to the predominant formation of the atm -diastereomeric reaction product. 

M. T. Reetz, Chelation or non-chelation control in addition reactions of chiral a- and (3-alkoxy carbonyl compounds, Angew. Chem. Int. Ed. Engl 23 556 (1984). 

Chelation or Non-chelation Control in Addition Reactions of Chiral a and B-Alkoxy Carbonyl Compounds"... 

Useful levels of stereoselectivity were obtained in intermolecular addition reactions of C(3)-sub-stituted allylsilanes to chiral aldehydes. Lewis acids that are capable of chelating to heteroatoms have been used to direct the stereochemical course of allylsilane a itions to a-alkoxy and a, -dialkoxy carbonyl compounds. The allylation of a-benzyloxy aldehyde (94) in the presence of TiCU and SnCl4 furnished products with high levels of syn stereoselection (. n-9. In contrast, under nonchelation-controlled reaction conditions (BF3-OEt2) allyltrimethylsilane reacted to form predominantly the anti-1,2-diol product (onri-95), as shown in Scheme 4S. 

Chiral auxiliary-bound substrates have also been used for the asymmetric process. The aldol reaction of chiral pyruvates such as 46 is a reliable method for highly enantioselective synthesis of functionalized tertiary alcohols (Scheme 10.38) [112]. The Lewis acid-catalyzed aldol-type reactions of chiral acetals with silyl enolates are valuable for the asymmetric synthesis of -alkoxy carbonyl compounds ]113, 114]. 

A similar reaction is found in the alkaline degradation of picrocrocin [(—)-4-hydroxy-2,6,6-trimethyl-l-cyclohexene-l-carboxaldehyde /3-n-glu-copyranoside] (XXXVIII) to n-glucose and safranal (2,6,6-tri-methyl-1,3-cyclohexadiene-l-carboxaldehyde) (XXXIX) (see Fig. 12). Picrocrocin does not contain a /3-alkoxy carbonyl system, but a proton may be easily removed from C3 of the aglycon by a base (because, as this compound is the vinylog of a d-alkoxy carbonyl compound, these protons behave as if they were adjacent to the carbonyl group). 

The relative energies of the intermediates and transition structures along the reaction coordinates are subject to the influence of solvation, which may alter relative stabilities and rates. This may explain the solvent effects discussed earlier (c/. Table 4.3, entries 1, 3 and 4). The energetic features outlined above may also explain the lack of selectivity in the nucleophilic additions to P-alkoxy carbonyl compounds. It is possible that even though 6-membered chelates are formed, their rates of formation are slower than addition via the nonchelated path, or that they are less reactive than a 5-membered chelate. Either of these circumstances (or a combination of both) would raise the transition state energy for the chelate path and the primary addition mode could be shifted to the less selective nonchelated mechanism. ... 

Ethyl tetrahydrofuran-2-carboxylates. p-Alkoxy carbonyl compounds in which the alkoxy group is readily detached in the presence of a Lewis acid undergo condensation with ethyl diazoacetate. Tin(IV) chloride is a suitable catalyst for P-alkoxy aldehydes, but it requires zirconium(IV) chloride to effect a reaction with P-alkoxy ketones. 

Barton, D.H.R., Jaszbetenyi, J.C., Lin, W. and Shinada, T. (1996) Oxidation of hydrazones hy hypervalent organoiodine reagents regeneration of the carbonyl group and facile syntheses of a-acetoxy and a-alkoxy azo compounds. Tetrahedron, 52, 14673-14688 (1997) Tetrahedron, 53, 14821, (erratum) Barton, D.H.R., Jaszbetenyi, J.C., Lin, W. and Shinada, T. (1996) The invention of radical reactions. Part XXXVI. Synthetic studies related to 3-deoxy-D-manno-2-octulosonic acid (KDO) Tetrahedron, 52, 2717-2726. 

CHELATION CONTROLLED ADDITIONS TO a AND P ALKOXY CARBONYL COMPOUNDS... 

Silyl enol ethers and ketene silyl acetals add to aromatic nitro compounds in the presence of TASF(Me) to give intermediate dihydro aromatic nitronates which can be oxidized with bromine or 2,3-dichloro-5,6-dicyano-l,4-benzoquinone to give a-nitroaryl carbonyl compounds the latter are precursors for indoles and oxindoles. The reaction is widely applicable to alkyl-, halo-, and alkoxy-substituted aromatic nitro confounds, including heterocyclic and polynuclear derivatives (eq 7). 

As an extension of this new procedure for carbon-carbon bond formation, the reaction between silyl enol ethers and acetals 50, a typical protecting group of aldehydes, is performed to afford j5-alkoxy carbonyl compound 51 in the presence of titanium(IV) chloride (Eq. (24)) [27]. A variety of substituted furans are readily prepared by application of the TiCU-promoted reaction of a-halo acetals 52 with silyl enol ethers (Eq. (25)) [27]. 

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