Enantioselective synthesis chlorination

This ligand has also been used by the same authors to promote the addition of ZnMe2 to a functionalised a,(3-unsaturated ketone in the asymmetric key step of the first enantioselective synthesis of (-)-frontalin. This synthesis started with the naphthalene-catalysed lithiation of a chlorinated ketal (Scheme 4.15) that, after several transmetalation processes, was trapped by reaction... 

The enzyme recLBADH is the first catalyst that has been found to allow the highly regio- and enantioselective synthesis of 5-hydroxy-P-keto esters by reduction of the respective diketo esters. This enzymatic reaction is of enormous preparative value. The substrates are readily available by acylation of P-keto ester bisenolates and the reaction only requires a simple batch technique which is easy to scale up. Reduction of the chlorinated compound la has been performed routinely on a 75 g scale in our laboratory (8 L fed batch), yielding (S)-2a in an isolated yield of 84% [10]. 

The successful application of sulfanyl amines in the diastereoselective and enantioselective synthesis of as-3,4-disubstituted /3-sultams has been reported (Scheme 56). The protocol is based on the oxidation of the 1,2-aminothiols 178 with hydrogen peroxide and ammonium heptamolybdate. Chlorination of the resulting /3-aminosulfonic acids was achieved using phosgene. The /3-aminosulfonyl chlorides 179 obtained were cyclized under basic conditions and without epimerization to yield the t -3,4-disubstituted /3-sultams 180 (>96% de, ee) (Table 13) <2005S1807>. 

The direct enantioselective a-chlorination of aldehydes leads to important intermediates 27 in organic synthesis (Scheme 2.34). This reaction was developed independently by two groups MacMillan et al. applied the salt of the imidazolidinone 3g as the catalyst, as i-proline was found to be a poor catalyst for this reaction (Scheme 2.34) [26a]. Various chlorinating reagents were tested, and the per-chlorinated quinone 28 was found to provide the best enantioselectivity. It was... 

An X-ray analysis of the titanium(IV) chloride complex53 of the acrylate of ethyl lactate shows that the. Re-face of the. rvn-periplanar Cx-C double bond is shielded by a chlorine atom, A cooperative effect is observed for the bis[ethyl (JS )-lactate] fumaric ester with cyclopentadi-ene54 This auxiliary has found an application in the enantioselective synthesis of sarkomycin methyl ester via a retro-Diels Alder reaction5". 

Catalytic enantioselective a-chlorination of carbonyl compounds, particularly, in organocatalytic synthesis of azacycHc compounds 13AJ0812. 

Enantioselective a-chlorination of cyclic /8-oxoesters was promoted by chiral amino diol derivatives. Optimization of the catalyst structure and the reaction conditions has allowed the synthesis of optically active products with high enantioselectivities (up to 96% ee) using inexpensive NCS as the chlorine source under irrild conditions (eq 35). ... 

An efficient asymmetric synthesis of the 3-substituted /3-sultams 163 has been reported. The key step of the synthesis is the Lewis acid-catalyzed aza-Michael addition of the enantiopure hydrazines (A)-l-amino-2-methoxy-methylpyrrolidine (SAMP) or CR,l ,l )-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]octane (RAMBO) to the alke-nylsulfonyl sulfonates 176. /3-Hydrazino sulfonates were obtained in good yield and excellent enantioselectivity. Cleavage of the sulfonates followed by chlorination resulted in the corresponding sulfonyl chlorides 177. The (A)-3-substituted /3-sultams 163 have been obtained in moderate to good yields and high enantioselectivity over two steps, an acidic N-deprotection followed by in situ cyclization promoted by triethylamine (Scheme 55) <2002TL5109, 2003S1856>. 

Widdowson has exploited the asymmetric deprotonation of 183 in a synthesis of a protected version 191 of the biaryl component of vancomycin, actinoidinic acid (Scheme 48) [110, 111]. One of the rings derives from an arenechromiiun tricarbonyl with stereochemistry controlled by asymmetric lithiation. The most readily lithiated position of 183, between the two methoxy groups, first needed blocking. Enantioselective lithiation and chlorination of 184 gave 186 (TMEDA was needed to displace sparteine from 185 and restore reactivity towards a poor electrophile). Suzuki coupling of 187 with the boronic acid 188 transfers planar... 

It took another 35 years until the first (and still the only known) enantioselective total synthesis of (/ )-ochratoxin a (326), and therefore of ochratoxins A and B, was published by Gill et al. in 2002 (264, 265). Scheme 6.1 shows six steps of the nine-step synthesis, which was achieved with 10% overall yield. The first three steps of the procedure are not shown and comprise the preparation of 327 from (/ )-2-methyloxirane according to ref. (266). Ketene dimethyl acetal and acetylenic ester 327 react in an intermolecular cycloaddition to give 328. This diene undergoes a Diels-Alder reaction with methyl propiolate to yield 329. Lactonization ( 330), demethylation ( 331), chlorination ( 332), and methyl ester cleavage finally furnished enantiomerically pure ochratoxin a (326) (267). 

You et al. investigated the enantioselective chlorocyclisation of indole-derived benzamides for the synthesis of spiro-indolines and fused indo-lines. (DHQD)2PHAL was used as catalyst, and DCDPH or l,3-dichloro-5,5-dimethylhydantoin (DCDMH) as chlorine source. 

Aldehyde donors were also employed successfully in the syntheses of convolutamydines E (77) and B (78) (80-82). The strategy was the same as depicted for the synthesis of (/ )- and (5)-convolutamydine A (32) (Scheme 9), but using acetaldehyde (79) instead of acetone (13) as the nucleophile in the cross-aldol reaction with dibromo-isatm 33 (Scheme 19). Nakamura et al. utilized catalyst 37, followed by a NaBH3CN-mediated reduction to obtain (/ )-convolutamydine E (77) in excellent yield and enantioselectivity. Chlorination of 77 then gave (l )-convolutamydine B (78) (Scheme 19) (80, 81). 

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