32346-07-9

Upstream product

• 75-77-4 chloro-trimethyl-silane 
• 101-41-7 benzeneacetic acid methyl ester 
• 40195-27-5 (1-methoxy-2-phenylvinyloxy)trimethylsilane 
• 27607-77-8 trimethylsilyl trifluoromethanesulfonate 

Downstream Products

• 14815-73-7 methyl allylphenylacetate 
• 88517-43-5 3-Benzyloxyamino-2-phenyl-propionic acid methyl ester 
• 94143-86-9 3-(1,1,1,3,3,3-Hexamethyl-disilazan-2-yl)-2-phenyl-propionic acid methyl ester 
• 112084-91-0 (2-Methyl-[1,3]dioxolan-2-yl)-phenyl-acetic acid methyl ester 
• 17147-72-7 [1,3]Dioxolan-2-yl-phenyl-acetic acid methyl ester 
• 112084-92-1 Phenyl-(2-phenyl-[1,3]dioxolan-2-yl)-acetic acid methyl ester 
• 113-45-1 dl-threo-methylphenidate 
• 113-45-1 methyl (R*)-2-phenyl-2-((S*)-piperidin-2-yl)acetate 
• 99092-02-1 methyl 3-amino-2-phenylpropanoate 
• 59845-64-6 3,3-dimethoxy-2-phenyl-propionic acid methyl ester 
• 1025769-75-8 methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,3-diphenylpropanoate 

Relevant academic research and scientific papers

Asymmetric syntheses of nakinadine D, nakinadine E, and nakinadine F: Confirmation of their relative (RS, SR)-configurations and proposal of their absolute (2 S,3 R)-configurations

The syn- and anti-diastereoisomeric forms of the reported structures of the marine alkaloids nakinadines D-F have been synthesized, for the first time in all cases, via an approach involving asymmetric Mannich-type (imino-aldol) reactions of methyl phenylacetate with N-tert-butylsulfinyl imines as the key steps to control the stereochemistry. Comparison of the 1H and 13C NMR spectroscopic data reported for the natural materials with those acquired for these synthetic samples confirms the initially assigned relative (RS,SR)-configurations of these three alkaloids. In the absence of specific rotation (or other diagnostic) data for the natural materials, it is not possible to unambiguously assign their absolute configurations, although given the absolute (2S)-configurations assigned to nakinadines B and C, and the absolute (2S,3R)-configuration previously established for nakinadine A, the data herein uphold our proposal that nakinadines D-F share the absolute (2S,3R)-configuration.

Synthetic strategies for the synthesis and transformation of substituted pyrrolinones as advanced intermediates for rhazinilam analogues

The biaryl core structure of rhazinilam with its fixed dihedral angle is a pivotal element for its unique in vitro cytotoxic activity. Most of the related natural products are oxidized versions of rhazinilam. Replacing the sensitive pyrrole ring by a pyrrolinone ring is the basis of our initial strategy towards rhazinilam analogues. With this goal, variants of the sequence crossed Mukaiyama aldol reaction followed by the Staudinger reaction were studied. Reacting a suitably substituted acetophenone with O-methyl O-trimethylsilyl ketene acetal gave pyrrolinones 8a and 8b in good to excellent yields. These intermediates could be transformed in four high-yielding steps into the pyrrolic precursors 7a-c containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam. Our studies illustrate a lack of stability of these intermediates. Alternative synthetic approaches towards this central biaryl core structure are described.

Copper-catalyzed amination of silyl ketene acetals with N-chloroamines

A copper(I)/2,2′-bipyridyl complex catalyzes an amination reaction of silyl ketene acetals with N-chloroamines, presenting a new preparative method of α-amino esters.

Highly enantioselective mannich reactions with α-aryl silyl ketene acetals and imines

Mannich reactions with chiral silicon Lewis acid activated acylhydrazones and α-aryl silyl ketene acetals and α-aryl,α-alkyl silyl ketene imines proceed efficiently and with good to excellent levels of both diastereoselectivity and enantioselectivity. The reactions provide access to α-aryl,β-hydrazido esters and α-aryl,α-alkyl,β- hydrazido nitriles, which are valuable analogs of β-amino acids.

MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-κB ACTIVITY AND USE THEREOF

Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity including inflammatory and immune diseases, obesity and diabetes having the structure of formula (I), its enantiomers, diastereomers, or a pharmaceutically acceptable salt, or hydrate, thereof, wherein X is (Ia); or X is (Ib); or X is (Ic); (Id) is heterocycle or heteroaryl; E is -N-, -NR1-, -O-, -S-, -SO2- or -CR2-; F is -N-, -NR1a-, -O-, -S-, SO2- or -CR2a-; G is N, -NR1b-, -O-, -S-, SO2- or -CR2b-, provided that the E-F-G containing heterocyclic ring formed does not contain a S-S or S-O bond, and at least one of E, F and G is a heteroatom; J, Ja, M, Ma, Q, Rx, Ry, R1, R1a, R1b, R2, R2a, R2b, and R3 to R21, Z, Za, Zb, and Zc are as defined above.

Uncatalyzed reaction of silyl ketene acetals with oxalyl chloride: A straightforward preparation of symmetrical pulvinic acids

(Chemical Equation Presented) Several natural pulvinic acids were synthesized. Silyl ketene acetals derived from methyl arylacetates (4 equiv) reacted with oxalyl chloride at -78°C, without the need of adding a catalyst. After treatment of the crude diketones with DBU and acidification with hydrochloric acid, symmetrical pulvinic acids methyl esters were obtained. Saponification of the methyl esters afforded the corresponding pulvinic acids in 60-70% overall yields from oxalyl chloride.

Synthesis of α-fluorocarboxylates from the corresponding acids using acetyl hypofluorite

α-Fluorocarboxylic esters and acids were synthesized in good yields. The corresponding esters and acids were converted to their ketene acetals, and these enol derivatives reacted with AcOF made directly from fluorine. This route circumvents the problems associated with nucleophilic fluorinations such as various eliminations and rearrangements. α- and β-branched carboxylic acid derivatives that cannot be directly fluorinated gave by this electrophilic fluorination the corresponding α-fluoro derivatives in good yield. Both the fluorination reaction and the preparation of AcOF are fast and suitable for [18]F incorporation into acids and esters needed for working with PET. α-Fluoroibuprofen (20) and methyl 2-fluoro-3,3,3-triphenylpropionate (32) are two examples of this general reaction.

Synthesis of germatranyl derivatives of esters of carboxylic acids via organometallic (Si, Ge, Sn) reagents

Trialkylstannyl esters of tris(2-hydroxyalkyl)amines, N(CH2CHROSnAlk3)3 (9-11) (R = H, Me; Alk = Et, Bu), react with X3GeC(R1)H(R2)COOR3 (12-17) (X = Cl or Br; R1, R2 = H, Me, Ph, SiMe3, COOEt; R3 = Me, Et) to give esters of α-germatranylcarboxylic acids, N(CH2CHRO)3GeQ(R1)MR2)-COOR 3 (1-8), in high yields. The synthesis of esters 12-17 is reported. Esters of α-germatranyldiphenylacetic acid 24 and 25 can be obtained by treatment of diphenylketene with Et3SnOMe to give in situ Et3SnC(Ph2)COOMe (23), followed by reaction with GeCL, to give in situ Cl3GeC(Ph2)COOMe (22) and further reactions with 9 or 11, respectively. Reduction of germatrane 6 with LiAlH4 in diethyl ether leads to cleavage of the germanium-carbon bond with subsequent formation of (2-hydroxyethyl)trimethylsilane. The crystal structures of 3, 6, and 7 are reported. 1-Acyloxygermatranes 26 and 27 are obtained by treatment of 1-methoxygermatrane (28) with diphenyl- and dichloroacetic acid, respectively. VCH Verlagsgesellschaft mbH,.

1,1′-binaphthalene-2,2′-diol as a chiral auxiliary. Diastereoselective alkylation of binaphthyl esters, complex-induced proximity effects in enolate formation, and one-step synthesis of an optically active β-substituted ketone

Diastereoselective alkylation of enolates derived from (S)-naphthyl phenylacetate 1 with LDA in THF gave the S,S-isomer as a major product. The diastereoselectivity increased as the bulkiness of the alkylating agent was increased. The low diastereomeric excess (～70%) of methylation was markedly raised to 92% by the use of n-BuLi as a base due to the complex-induced proximity effect (CIPE) in enolate formation. This highly diastereoselective methylation was used to synthesize the clinically important anti-inflammatory drugs (S)-naproxen (60) and (S)-suprofen (68). The stereochemistry of ketene trimethylsilyl acetals generated from several phenylacetates was investigated to understand the origin of the diastereoselectivity in this alkylation. Methyl phenylacetate (46) predominantly gave a (Z)-enolate by kinetic deprotonation, while the (E)-enolate was predominantly obtained from phenyl phenylacetate (47). An optically active ketone (88) was synthesized from binaphthyl ester 84 by a one-pot procedure involving the 1,4-addition, followed by the 1,2-addition, of organometallics. The CIPE again played a crucial role in the high enantiomeric excess in this case.

Stereochemistry of Silyl Ketene Acetals of Some 8-Phenylmenthyl Arylacetates

Trimethylsilyl ketene acetals derived from 8-phenylmenthyl phenyl-, p-fluorophenyl, and p-(trifluoromethyl)phenylacetates, methyl phenylacetate, and isopropyl phenylacetate have been studied.It was shown that it is not possible, under kinetic conditions, to form exclusively the desired E-isomer and that the thermodynamic Z-isomer is also obtained as the major product under reaction conditions which can be considered kinetic.The results could be rationalized using the Ireland's and Dauben's models on the basis of the changes in the acidity of the proton to be abstraced and the strength of the base.Dimethyl-tert-butylsilyl ketene acetals have been studied.It appeared that reaction of TBDMSCl onto the Li-enolates favored the E-isomer.We proposed that, at the temperature (above -20 deg C) at which the reaction occurs, the E-Z equilibrium between the Li-enolates starts to play a role, and therefore the silyl ketene acetals E/Z ratios are kinetically controlled but by the second step (reaction of the reagent onto the Li-enolate).