A [Pd]-mediated ω-alkynone cycloisomerization approach for the central tetrahydropyran unit and the synthesis of C(31)–C(48) fragment of aflastatin A

Abstract

A concise assembly of the central tetrahydropyran unit of aflastatin A featuring a Pd-mediated alkynone cycloisomerization to provide a glycal and its subsequent stereoselective hydroboration to deliver the requisite stereochemistry at C(33) and C(34) centers is documented.

Regioselective Wacker Oxidation of Internal Alkenes: Rapid Access to Functionalized Ketones Facilitated by Cross‐Metathesis

“…At the outset of our investigations, we reasoned that the allylic heteroatom placed in close proximity to the alkene could provide an efficient handle to induce the desired regioselectivity. [8] Previous examples of directed Wacker oxidations of internal alkenes have been limited by low yields, use of peroxide as oxidants, and high oxygen pressure, and were limited in scope. [6,8] In addition, only recently have efficient catalyst systems for the Wacker oxidation of internal alkenes been developed.…”

First Total Synthesis of Gliomasolide C and Formal Total Synthesis of Sch-725674

“…Deuterated solvents for NMR spectroscopic analyses were used as received. All 1 H NMR and 13 C NMR spectra were obtained using a 200, 400, or 500 MHz spectrometer. Coupling constants were measured in hertz.…”

“…The crude product was purified by flash chromatography over 200−400 mesh silica gel (15% EtOAc/ Petroleum ether) to afford hydroxyl ester 10 (145 mg, 82%) as a light yellow oil. [α] D 26 +27.54 (c 0.16, CHCl 3 ); IR υ max (film): 3450, 3015, 1708, 1371, 1257 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 6.79 (dd, J = 15.6, 5.4 Hz, 1H), 6.05 (dd, J = 15.6, 1.5 Hz, 1H), 5.78 (td, J = 15.3, 6.8 Hz, 1H), 5.36−5.26 (m, 1H), 4.73−4.65 (m, 2H), 4.00 (q, J = 7.1 Hz, 2H), 3.64−3.52 (m, 1H), 2.11−2.01 (m, 2H), 1.53 (s, 3H), 1.37 (s, 3H, merged with multiplet), 1.43−1.24 (m, 19H), 0.89 (t, J = 7.0 Hz, 3H); 13 Ethyl(E)-3-((4R,5S)-5-((R)-8-hydroxy-2-oxotridecyl)-2,2-dimethyl-1,3-dioxolan-4-yl)acrylate (11). PdCl 2 (24 mg, 0.13 mmol) was added to a solution of dimethylacetamide (20 mL), H 2 O (2.0 mL) in a 100 mL Parr steel reactor, and the resulting solution was stirred under 200 psi O 2 pressure for 1 h at rt.…”

“…The crude product was purified by flash chromatography over 200−400 mesh silica gel (20% EtOAc/ Petroleum ether) to afford keto alcohol 11 (56 mg, 54%, 76%, based on recovery of starting material) as a light yellow oil. [α] D 25 +6.68 (c 0.86, CHCl 3 ); IR υ max (film): 3420, 2930, 1715, 1654, 1217 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 6.70 (dd, J = 15.4, 5.8 Hz, 1H), 6.05 (dd, J = 15.6, 1.2 Hz, 1H), 4.83−4.79 (m, 1H), 4.70 (q, J = 6.8 Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 3.57−3.54 (m, 1H), 2.75 (dd, J = 17.4, 6.4 Hz, 1H), 2.48 (dd, J = 17.2, 7.2 Hz, 1H), 2.43−2.33 (m, 2H), 1.60−1.50 (m, 2H), 1.49 (s, 3H), 1.44−1.37 (m, 5H), 1.36 (s, 3H), 1.35−1.19 (m, 12H), 0.88 (t, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 208.3, 165.9, 142.9, 123.4, 108.9, 76.6, 73.9, 71. (E)-3-((4R,5S)-5-((R)-8-Hydroxy-2-oxotridecyl)-2,2-dimethyl-1,3-dioxolan-4-yl)acrylic Acid (12).…”

“…After a few failed attempts, Wacker oxidation 13 under high oxygen pressure (200 psi O 2 , 0.5 equiv of PdCl 2 , 70 °C in DMA:H 2 O for 14 h) afforded desired ketone 11 in a highly regioselective manner. It is worth mentioning that, in a very few occasions, these kinds of transformations were documented in the literature.…”