First Asymmetric Synthesis of New Diarylheptanoids, Renealtin A and B, with a Tetrahydrofuran Ring

Abstract

An efficient and convenient process is described for the first preparation of a new diarylheptanoid, renealtin A, isolated from the seeds of the Brazilian medicinal plant Renealmia exaltata. The key trisubstituted tetrahydrofuran ring was constructed through Lewis acid mediated stereoselective allylation of the lactol derivative by featuring the elaboration of the functionalized homochiral lactone derived from l-tartaric acid. The synthesis of the other ­minor stereoisomer, renealtin B, was also established.

Key words

natural product - diarylheptanoid - trisubstituted tetra­hydrofuran - C ₂-imide - tartaric acid

References and Notes

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• These stereochemical results are in good accord with those of the recently reported following references in which the allylation products were formed by stereoelectronically preferred inside attack on the lowest energy conformer; see:
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• 17d The studies mentioned in these preceding reports indicate in detail that a knowledge of the unusual con-formational preferences of alkoxy groups in oxocarbenium ions and a stereoelectronic model to explain reactions of five-membered-ring oxocarbenium ions can be combined to predict selectivities in highly substituted oxocarbenium ions and also iminium ions

13

Absolute stereochemistry of obtained 11 was easily determined by comparing its chemical shifts of ¹H NMR and ¹³C NMR spectral data with those of our preceding compounds.¹²
Spectral Data for 11.
[α]_D ²⁵ +73.0 (c 1.00, MeOH). ¹H NMR (CDCl₃): δ = 7.31-7.15 (m, 5 H), 6.69-6.59 (m, 2 H), 4.94 (s, 2 H), 4.66 (br, 1 H), 4.62 (dd, 1 H, J = 11.7, 7.3 Hz), 4.26 (br t, 1 H), 4.03 (br s, 2 H), 3.69 (s, 3 H), 2.97 (dd, 1 H, J = 14.7, 4.4 Hz), 2.72 (dd, 1 H, J = 14.7, 7.9 Hz). ¹³C NMR (CDCl₃): δ = 175.8, 149.4, 147.1, 137.0, 129.3, 128.5, 127.9, 127.3, 122.0, 114.1, 113.7, 81.5, 73.7, 73.0, 71.1, 56.1, 34.4. Anal. Calcd for C₁₉H₂₀O₆: C, 66.27; H, 5.85. Found: C, 66.15; H, 5.91.

15

It is well known that these types of allylation reactions via substituted oxocarbenium ions do not necessarily afford the corresponding products with good stereoselectivity, but instead lead to lower non-stereoselective results in some cases. It mainly depends on the three factors such as the position and the number of substituents in those oxocarbenium ions employed as well as their configurations, see ref. 17. Our satisfactory stereoselective findings at this stage prompted a further search for practical synthesis of the targeting natural products.

16

Stereochemistry of the generated stereogenic centers of 14b and 15b was determined unambiguously based on its chemical shifts of the protons at the C-1 position, even though showing multiplet signals; 14b: δ = 4.26-4.40 (m, 1 H) ppm, 15b: δ = 4.49-4.59 (m, 1 H) ppm.^10,17 Compound 14a was also estimated to have the same configuration based on the similarity of its spectral data to those of 14b.

18

Experimental Procedure for the Crude Synthesis of the Coupling Product Employing 16 with Aryllithium Reagent.
To a solution of 4-benzyloxy-3-methoxybromobenzene (0.30 g, 1.02 mmol) prepared through benzylation of commercially available 4-bromo-2-methoxyphenol (Aldrich) in 3 mL of Et₂O-THF (5:1) was added 1.60 M BuLi hexane solution (0.65 mL, 1.04 mmol) at -78 °C under argon. After the mixture was stirred for 10 min, a solution of the aldehyde intermediate 16 (0.297 g, 0.50 mmol) cleaved with NaIO₄ via dihydroxylation of 14b in 0.5 mL of THF was added, and the reaction mixture was further stirred for 1 h at the same temperature. Then, the mixture was quenched by the addition of sat. NH₄Cl solution (3 mL) and extracted with EtOAc (3 ¥ 50 mL). The combined organic layers were dried (Na₂SO₄) and concentrated in vacuo, which were used in the following oxidation reaction without further purification.