Solvents stereoselective synthesis

I. Solvent-Dependent, Kinetically Controlled Stereoselective Synthesis of 3- and 4-Thioglycosides... 

Dynamic Resolution of Chirally Labile Racemic Compounds. In ordinary kinetic resolution processes, however, the maximum yield of one enantiomer is 50%, and the ee value is affected by the extent of conversion. On the other hand, racemic compounds with a chirally labile stereogenic center may, under certain conditions, be converted to one major stereoisomer, for which the chemical yield may be 100% and the ee independent of conversion. As shown in Scheme 62, asymmetric hydrogenation of 2-substituted 3-oxo carboxylic esters provides the opportunity to produce one stereoisomer among four possible isomers in a diastereoselective and enantioselective manner. To accomplish this ideal second-order stereoselective synthesis, three conditions must be satisfied (1) racemization of the ketonic substrates must be sufficiently fast with respect to hydrogenation, (2) stereochemical control by chiral metal catalysts must be efficient, and (3) the C(2) stereogenic center must clearly differentiate between the syn and anti transition states. Systematic study has revealed that the efficiency of the dynamic kinetic resolution in the BINAP-Ru(H)-catalyzed hydrogenation is markedly influenced by the structures of the substrates and the reaction conditions, including choice of solvents. 

A solvent-free photooxygenation of 5-methoxyoxazoles 169 embedded in porphirin-loaded polystyrene beaded as solid support resulted in 3//-1,2,4-dioxa/olcs 170 as sole products in good yields. Stereoselective synthesis of a-amino carboxylic acids derivatives 171 was developed by acid catalyzed hydrolysis of compounds 170 (Scheme 45) <2005JCR422>. 

Nacci, whose procedure involved the use of the ionic solvent n-butylpyridinium tetrafluoroborate, reported a stereoselective synthesis of 2,3-dihydrofurans <03JOC4406>. 

Both intermolecular and intramolecular additions of carbon radicals to alkenes and alkynes continue to be a widely investigated method for carbon-carbon bond formation and has been the subject of a number of review articles. In particular, the inter- and intra-molecular additions of vinyl, heteroatomic and metal-centred radicals to alkynes have been reported and also the factors which influence the addition reactions of carbon radicals to unsaturated carbon-carbon bonds. The stereochemical outcome of such additions continues to attract interest. The generation and use of alkoxy radicals in both asymmetric cyclizations and skeletal rearrangements has been reviewed and the use of fi ee radical reactions in the stereoselective synthesis of a-amino acid derivatives has appeared in two reports." The stereochemical features and synthetic potential of the [1,2]-Wittig rearrangement has also been reviewed. In addition, a review of some recent applications of free radical chain reactions in organic and polymer synthesis has appeared. The effect of solvent upon the reactions of neutral fi ee radicals has also recently been reviewed. ... 

There are a few efficient methods for the stereoselective synthesis of vinyl halides, and this transformation remains a synthetic challenge. Research by S. Roy showed that the Hunsdiecker reaction can be made metal free and catalytic catalytic Hunsdiecker reaction) and can be used to prepare ( )-vinyl halides from aromatic a,p-unsaturated carboxylic acids. The unsaturated aromatic acids were mixed with catalytic amounts of TBATFA and the A/-halo-succinimide was added in portions over time at ambient temperature. The yields are good to excellent even for activated aromatic rings which do not undergo the classical Hunsdiecker reaction. The fastest halodecarboxylation occurs with NBS, but NCS and NIS are considerably slower. The nature of the applied solvents is absolutely critical, and DCE proved to be the best. This strategy was extended and applied in the form of a one-pot tandem Hunsdiecker reaction-Heck coupling to prepare aryl substituted (2 ,4 )-dienoic acids, esters, and amides. 

Wang, H., Zhao, X., Li, Y. and Lu, L. (2006) Solvent-controlled asymmetric Strecker reaction stereoselective synthesis of a-trifluoromethylated a-amino acids. Org. Lett., 8, 1379-1381. 

Loh et al have demonstrated the stereoselective synthesis of 1,3-amino alcohols based on the InCla-catalyzed Mukaiyama aldol reaction of a keto ester under solvent-free conditions. The high selectivity has been explained by the influence of a remote group present in the keto ester (Scheme 5.45). 

The synthesis of the azetidin-2-one nucleus, via the classical annulation of acetyl-chlorides with imines, requires more than stoichiometric amounts of Uiethylamine (about 3 equivalent), which cannot be recovered and reused. In addition, the procedure needs a large amount of organic solvents (VOCs) and, as a consequence, causes a large amount of waste. To overcome these difficulties, the possible ytterbium (III) triflate-catalysed stereoselective synthesis of P-lactams via [2+2] cyclocondensation in ionic liquids has been investigated by Su et al. (Scheme 16.4) [93]. 

Scheme 9 Stereoselective synthesis of di-D-fmctofuranose l,2 2,l -dianhydrides from 1,2-iso-propylidene-P-D-fructofuranose precursors by selective acidic activation in organic solvents...

Figure 12. Stereoselective synthesis of naproxen. Reagents a, (21 ,3R)-dialkyltartrate, MeSO,H, MeOiCIl b, Bt2, solvent c, NaOH, H20, solvent d, H20 adjusted to pH 411-5.5 e, H2, catalyst.

A stereoselective synthesis of five- to seven-membered cyclic ethers has been achieved by de-iodonative ring-enlargement of cyclic ethers having an iodoalkyl substituent. For example, the reaction of tetrahydrofuran derivative 360 with (diacetoxyiodo)toluene proceeds under mild conditions to afford ring-expanded product 361 (Scheme 3.144). The use of hexafiuoroisopropanol (HFIP) as solvent in this reaction is critical [462]. 

---