Kapa Prasad

Mild and regioselective oxidative bromination of anilines using potassium bromide and sodium perborate

Abstract The selective monobromination of various deactivated anilines using potassium bromide and sodium perborate as oxidant has been achieved. The use of ammonium molybdate as catalyst accelerates the rate of reaction but is not essential to obtain good yields and high selectivities.

Enantioselective acylation of β-aminoesters using penicillin G Acylase in organic solvents

Abstract The resolution of racemic β-aminoesters has been achieved through selective acylation catalyzed by Penicillin G Acylase (ChiroCLEC TM -EC). The method has been optimized using three different phenylacetyl donors, and the effect of solvents on the rate of reaction is described. The efficiency of our method is illustrated by the synthesis of five different β-aminoesters with high enantiomeric purities.

ASYMMETRIC SYNTHESIS OF 3,5-DIHYDROXY-6(E)-HEPTENOATE-CONTAINING HMG-COA REDUCTASE INHIBITORS

Abstract A ‘one-pot’ conversion of aldehyde 6 to hydroxyketoester 10 with high enantioselection, culminating in a practical asymmetric synthesis of (3 R ,5 S ) isomer of the antihyperlipoproteinemic agent fluvastatin, 1 , is described. All four 3,5-dihydroxy-6( E )-heptenoate stereoisomers were prepared in enantiopure form starting from 10 , utilizing selective reduction and oxidation methods.

Asymmetric Synthesis of Homoallylic Amines Bearing Adjacent Stereogenic Centers by Addition of Substituted Allylic Zinc Reagents to N-tert-Butanesulfinylimines†

A highly diastereoselective addition of substituted racemic allylic zinc reagents to chiral N- tert-butanesulfinylimines resulting in the formation of homoallylic amines is reported. This method is quite general and also efficient for the preparation of enantiomerically pure homoallylic amines bearing quaternary centers and also adjacent quaternary centers.

An Unexpected Reaction of Arenesulfonyl Cyanides with Allylic Alcohols: Preparation of Trisubstituted Allyl Sulfones

For an ongoing program within our research group we needed to synthesize sulfinates of the type 1. We reasoned that 1 could be easily prepared by a reaction of Baylis– Hillman adduct 3 with p-toluenesulfonyl cyanide (Scheme 1). These reaction conditions, however, led to an unexpected trisubstituted allyl sulfone 2. To the best of our knowledge, such a reaction of a Baylis–Hillman adduct with ptoluenesulfonyl cyanide 3] to form substituted allyl sulfones has not been reported. These types of substituted allyl sulfones are important intermediates in organic synthesis and have been recently found to be highly potent against cancer and abnormal cell proliferation diseases. The synthesis of these substituted compounds has received scant attention in the literature, with only two methods outlined. Kabalka et al. reported the nucleophilic addition of sodium p-toluene sulfinate to an acetate of the Baylis–Hillman adduct, and found that the reaction only proceeded in ionic liquids at high temperatures. Later, Chandrasekhar et al. reported a nucleophilic addition of sodium p-toluene sulfinate to the Baylis–Hillman adduct in polyethylene glycol as the solvent at high temperatures. It is therefore significant that the new method we report herein is unprecedented, quite general, and proceeds efficiently at ambient temperature. Treatment of methyl 2-(hydroxyphenylmethyl) acrylate (3a, 1 equiv) with p-toluenesulfonyl cyanide (4b, 1.2 equiv) in the presence of diisoproylethylamine (1.3 equiv) in dichloromethane at room temperature for 12 hours afforded trisubstituted allyl sulfone 2a in high yield (92 %) with good selectivity (E/Z 5:95; Table 1, entry 1). The structure of 2a was assigned based on H,C NMR spectroscopy and mass spectrometry as well as by comparison with literature data. The E/Z ratio was determined to be 5:95 by H NMR analysis of the crude product. Similarly, the reaction of 3a with benzenesulfonyl cyanide (4 a) in the presence of iPr2NEt in CH2Cl2 at room temperature for 12 hours also proceeded to give the trisubstituted allyl sulfone 2b in 95 % yield and with an E/Z ratio of 6:94 (Table 1, entry 2). Encouraged by these results, we turned our attention to other substituted aromatic acrylates. Interestingly, a large number of these acrylates such as p-methyl, o-bromo, cinnamyl, and furfuryl derivatives reacted cleanly with benzenesulfonyl cyanide (4a) or p-toluenesulfonyl cyanide (4b) in the presence of base leading to the corresponding trisubstituted allyl sulfones 2c–2h (Table 1, entries 3–8) in high yields (80–86 %) and with good selectivity (E/Z ratio from 6:94 to 2:98). In the same way, aliphatic Baylis–Hillman adducts such as methyl 3-hydroxy-2-methylenehexanoate (3 f) and methyl 3-hydroxy-2-methyleneoctanoate (3 g) reacted smoothly with 4 a to afford the corresponding trisubstituted allyl sulfones 2 i (75 % yield) and 2j (72% yield) with an E/Z ratio of 7:93 and 6:94, respectively (Table 1, entries 9 and 10). Interestingly, the reaction of other Baylis–Hillman adducts such as 3-(hydroxymethylphenyl)but-3-en-2-one (3h) with 4a in the presence of iPr2NEt in CH2Cl2 at room temperature for 12 hours afforded trisubstituted allyl sulfone 2k in high yield (85 %) and with high selectivity (E/Z 5:95; Table 1, entry 11). Likewise, the reaction of 4a with 2Scheme 1. Reaction of arenesulfonyl cyanides with various allylic alcohols. Scheme 2. A possible mechanism and conformations.

New observations on peptide bond formation using CDMT

Abstract The optimized formation of the peptide bond by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) has been found to occur rapidly and essentially quantitatively in a one-pot, one-step procedure. This new method is effective for the coupling of a variety of reactive partners, including chiral amino acids (e.g. N -acetyl- l -leucine) without significant loss of configuration. Significant racemization was observed when the typical literature conditions were used, due to the formation of an azlactone intermediate which is configurationally unstable under the reaction conditions. A simpler, precipitative workup procedure is also disclosed in this report.

A practical synthesis of enantiopure ethyl cis-2-amino-1-cyclohexanecarboxylate via asymmetric reductive amination methodology

Abstract A simple and practical method for large scale preparation of optically pure ethyl 2-amino-1-cyclohexanecarboxylate was developed via a reductive amination of 2-oxo-cyclohexanecarboxylate with a chiral α-methylbenzylamine. The major diastereomer was isolated in optically pure form by a simple and efficient crystallization as its HBr salt. The diastereoselectivity as well as the cis trans selectivity was also improved.

The enantioselective reduction of 2'-fluoroacetophenone utilizing a simplified CBS-reduction procedure

Abstract We have developed a practical, non-enzymatic, catalytic process for the enantioselective reduction of 2′-fluoroacetophenone. A number of catalysts were screened for the oxazaborolidine-type reduction of this ketone to obtain an optimized system. We have shown that the simplest procedure uses the catalyst formed in situ from ( S )-α,α-diphenyl-2-pyrrolidinemethanol (( S )- 2 ) and borane–diethylaniline.

In-situ generation of Et3SiBr from BiBr3 and Et3SiH and its use in preparation of dialkyl ethers

Abstract The reported BiBr 3 –Et 3 SiH catalyzed reductive etherifications of silyl ethers with carbonyl compounds are shown to be catalyzed by the in situ formed Et 3 SiBr and verified by an independent use of the commercial reagent. As Et 3 SiBr is moisture sensitive and is not readily available, this in situ generation is still recommended as the method of choice. Utilizing this method, several alcohols were transformed under very mild conditions into dialkyl ethers via their silyl intermediates, such as TES, TBDMS, and TIPS.

The synthesis of (R)- and (S)-α-trifluoromethyl-α-hydroxycarboxylic acids via enzymatic resolutions

Abstract Kinetic resolution of 1,1,1-trifluoro-2-alkanone cyanohydrin acyl derivatives with Candida rugosa lipase afforded the remaining ( R )-enantiomer in high selectivity (E from 30 to >200). Candida rugosa lipases from several suppliers were compared and found to differ remarkably in their selectivity. The ( R )-enantiomer was hydrolyzed in one step to yield optically pure ( R )-α-trifluoromethyl-α-hydroxycarboxylic acids in excellent yield. The ( S )-acids were obtained in good e.e. by subtilisin-catalyzed resolution of the corresponding racemic esters followed by chemical hydrolysis of the remaining ( S )-esters.