Glycolate, asymmetric alkylation

Conversion of 2 to the highly crystalline oxazolidinone 3 with phosgene has been described by Thornton who has employed this substance as a chiral auxiliary in asymmetric aldol reactions of its N-propionyl derivative. Kelly has also used an oxazoline derived from 3 as a chiral auxiliary in asymmetric alkylation of a glycolate enolate. Oxazolidinone 3 has also been prepared from 2 with diethyl carbonate in the presence of potassium carbonate. The conversion of 2 to the oxazolidinone 3 is accomplished using triphosgene in this procedure because of the high toxicity of phosgene. 

The continued fascination chemists possess with asymmetric synthesis provides the basis for the next four procedures. The synthesis of (R)-(-)-10-METHYL-l(9)-OCTALONE-2 is a nice demonstration of an asymmetric Michael addition by a chiral imine followed by an aldol—in short an asymmetric Robinson annulation. The asymmetric glycolization to STILBENE DIOL (R,R-l,2-DIPHENYL-I,2-ETHANEDIOL) represents an olefin oxidation using catalytic alkaloids in tandem with osmium tetroxide. As reagents for a variety of asymmetric alkylations, the preparation of 2-CYANO-6-PHENYLOXAZOLOPIPERIDINK is pavscnicd as well as another route to... 

Benzyloxylactic acid (274) is accessible in two steps via asymmetric alkylation of glycolic acid derivative 272. Methylation of 272 proceeds in high yield to give 273 with 97% de. Other alkylating agents such as benzyl bromide, 1-iodobutane, 1-iodooctane, or isopropyl... 

Other examples of shown effectiveness of PTCs were reported by Park, Jew, and co-workers [98], They developed enantioselective synthetic method for the preparation of (/ )-a-alkylserines and (S)-a-alkylserines based on asymmetric alkylation of phenyl or o-biphenyl oxazoUne derivatives using CBPTC XXXXVIa and binaphthol-derived Maruoka s catalyst XXV, respectively (Scheme 8.16). The same authors [99] also expanded this methodology to enantioselective synthesis of (/ )-a-alkylcysteines and (5)-a-alkylcysteines using thiazoline-4-carboxylates in PTC alkylation. In 2006, Maruoka and co-workers [100] reported first example of the catalytic asymmetric alkylation of glycolates that establishes stereogenic quaternary carbon centers (Scheme 8.17). Their approach utilized 3,5-diaryloxazolidin-2,4-diones 48 as novel... 

In subsequent reports [87], the principle of asymmetric glycolate alkylation/ RCM sequence was applied to the first total synthesis of isolaurallene (172), that contains a densely functionalized A5-oxonene core (Scheme 32). Anticipating that the gearing effect created by two synergistic gauche effects at C6-C7 and... 

The asymmetric a-alkylation of carbonyl compounds is a fundamental reaction. Under PTC conditions, acidic substrates such as phenylketone derivatives can be used to create chiral stereogenic centers. Andrus demonstrated asymmetric glycolate alkylation with up to 90% ee using various electrophiles and its application to the synthesis of (-)-ragaglitazar in six steps (Scheme 3.16) [37-39]. 

Fig. 11.13. Regioselectivity of the pinacol rearrangement of an asymmetric glycol. The more stable carbenium ion is formed under product-development control. Thus, the benzhydryl cation B is formed here, while the tertiary alkyl cation D is not formed.

A highly efficient synthesis of the marine metabolite laurencin (3.12) involves asymmetric glycolate alkylation (Scheme 3.5). 

Ligands have also been attached to polyethylene glycol so that they can be recovered for recycle by the foregoing methods. A phosphine isocyanate has been reacted with polyethylene glycol for use in the Staudinger reaction with alkyl azides to form a phosphine imine.173 An alkaloid has been attached to the monomethyl ether of polyethylene glycol for use in the Sharpless asymmetrical dihydroxylation of olefins. The reaction was complete in the same time, with no decrease in yield or enantioselectivity, as when the alkaloid was used by itself.174 (Asymmetrical reactions are covered in Chap. 10.)... 

Several new chiral modifications of lithium aluminium hydride have been reported, including those formed by reaction with chiral secondary benzylamines (14), with diols such as (15) derived from D-mannitol, or with terpenic glycols such as (16). These complexes reduce phenyl alkyl ketones to optically active phenyl carbinols, and enantiomeric excesses of up to 50% have been observed in the case of reagents derived from (14). However, in the diol complexes, believed to have structures of the type shown in (17), lower chiral selectivity is observed, e.g. up to ca. 12% in the case of (15), or up to an optical yield of 30% with an ethanol-modified complex of (16). Better results have been reported with the chiral diamine complex (18), derived originally from L-proline, which reduces acetophenone in 92% optical yield. Asymmetric induction with reagents in this class (i.e. derivatives of lithium aluminium hydride) is usually low in the reduction of aliphatic ketones, but a complex of UAIH4 and the amino-alcohol (19) has been shown to reduce... 

Triphase catalysts were also used for C-alkylations (Komeili-Zadeh, 1978) and have been shown to promote asymmetric addition in carbene addition reactions (Chiellini and Solaro, 1977 Colonna et al., 1978). Ammonium groups have been replaced by phosphoric triamides (Tomoi et al., 1978), phosphonium groups (Tundo, 1978), and polyethylene glycol (Regen and Dulak, 1977) to provide alternate phase-transfer agents. 

Another PFTase inhibitor kurasoin B 79, which was isolated from the fungus, Paecilomyces sp., was also synthesized by means of the asymmetric glycolate alkylation (Scheme 4.18). The bishydrocinchonidinium salt PTC 2... 

Andrus MB, Hicken EJ, Stephens JC, Bedke DK. Asymmetric phase-transfer catalyzed glycolate alkylation, investigation of the scope, and application to the synthesis of (—)-ragaglitazar. J. Org. Chem. 2005 70(23) 9470-9479. 

Crimmins, M.T., Stanton, M.G., and Allwein, S.P. (2002) Asymmetric total synthesis of (—)-laulimalide exploiting the asymmetric glycolate alkylation reaction. J. Am. Chem. Soc., 124, 5958-5959. 

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