tert-Butyl 3-Oxo-4-(phenylsulfinyl)-2-(triphenyl-λ⁵-phosphanylidene)butanoate: A New Reagent for the Efficient Synthesis of Triphenylphosphorane Ylide Precursors to Vicinal Tricarbonyls from Alkyl Halides

Abstract

Vicinal tricarbonyl units1 have been attractive and challenging research topics for synthetic and medicinal chemists not only because of the presence of these units in many bioactive natural products e.g., FK-506, 2a rapamycin, 2b eurystatin, 2c and cyclotryprostatin, 2d but also because of the superb usefulness of these units for the synthesis of heterocyclic compounds.3 Therefore, a lot of efforts have been devoted to developing these highly electrophilic units.4 Wasserman et al. reported an unique synthetic route in which triphenylphosphorane ylides 2, valuable precursors to vicinal tricarbonyls, are introduced in a convergent manner and then oxidized under mild reaction conditions (Scheme 1). 5Despite the wide application of this route for the synthesis of complex molecules, 3,6 the key intermediates 2 should have been prepared only from carboxylic acids and acid chlorides. In order to circumvent this limitation and widen the scope, we have recently developed a new synthetic approach to triphenylphosphorane ylides (5 & 2') from carbonyl compounds utilizing a new Horner-WadsworthEmmons (HWE) reagent 4 (Scheme 2). 7In a related study recently reported, 8 we have devised a new synthetic approach to cyanophosphorane ylides, precursors to α-keto amide/ester in Wasserman's protocol, from alkyl bromides utilizing a new sulfinyl reagent with α-keto cyanophosphorane subunit based on sulfoxide chemistry. 9As an extention of this strategy for the synthesis of triphenylphosphorane ylide precursors (5 & 2') from chemicals other than carboxylic acids and acid chlorides, herein we wish to report another new synthetic route for triphenylphosphorane ylides 5 from alkyl halides utilizing a new sulfinyl reagent 6 as the key reagent (Scheme 3). Results and DiscussionThe new sulfinyl reagent 6 was prepared successfully from phenylsulfinylacetic acid and commercially available (tert-butoxycarbonylmethylene)triphenylphosphorane 1 according to our reported procedure 8 in 81% yield, and the representative results of our new approach using 6 as the key reagent are summarized in Table 1.To get the optimum reaction conditions, NaH and benzyl chloride were tested first for the alkylation reaction. Although enolization of 6 was accomplished with a little excess of NaH (1.3 eq) in THF under mild conditions (rt, 15 min), alkylation of the resulting enolate with benzyl chloride (1.1 eq) was found to be almost inactive (ca. 10% progress) (run 1). Benzyl bromide, however, reacted smoothly with the resulting enolate under the same conditions to provide two diastereomeric alkylated intermediates 7a (R = -Ph). These diastereomeric alkylated intermediates 7a were separated by flash column chromatography (SiO 2 , CH 2 Cl 2 /EtOAc = 2/1), and their structure were confirmed by 1 H-NMR in which each methine proton next to carbonyl and sulfinyl moieties appears in the downfield region of 5.91 ppm (dd, J 1 = 11.2 Hz, J 2 = 3.9 Hz) and 5.97 ppm (dd, J 1 = 11.5 Hz, J 2 = 3.2 Hz), respectively. For the conversion of 7a to 5a, 7a was treated first in reflu...

Picolinic acid promoted oxidative decarboxylation of phenylsulfinylacetic acid by Cr(VI)

“…Though phenylsulfinylacetic acid (PSAA) is a versatile compound finding utility in pharmaceutical and synthetic fields [20][21][22][23][24][25][26], literature survey clearly reveals that there is no systematic mechanistic study on the oxidation of PSAA except our recent publications [27][28][29][30][31]. Hence, in continuation of our work it is decided to carry out a systematic investigation on the PA promoted Cr(VI) reaction with PSAA with a view to proposing a suitable mechanistic path.…”

Spectral Evidence for the One-Step Three-Electron Oxidation of Phenylsufinylacetic Acid and Oxalic Acid by Cr(VI)

“…In the case of co-oxidation of S-phenylmercaptoacetic acid and oxalic acid with pyridinium chlorochromate [19], two different mechanisms, based on substrate concentration, have been suggested. The significant utility of phenylsulfinylacetic acid (PSAA) in various synthetic routes [20][21][22][23][24][25][26] prompted the present investtigation. Detailed literature scanning also reveals that there is no systematic kinetic report on PSAA and so, the present study of Cr(VI) co-oxidation of PSAA with oxalic acid (OxH 2 ) is undertaken and its salient features along with the substituent effects are discussed .…”