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. 2015 Nov 14;13(42):10466-70.
doi: 10.1039/c5ob01808k. Epub 2015 Oct 6.

Synthesis of virtually enantiopure aminodiols with three adjacent stereogenic centers by epoxidation and ring-opening

Lan Luo  1 , Hisashi Yamamoto
Affiliations

Synthesis of virtually enantiopure aminodiols with three adjacent stereogenic centers by epoxidation and ring-opening

Lan Luo et al. Org Biomol Chem. .

Abstract

A virtually complete enantioselective synthesis of 3-amino-1,2-diols with three consecutive stereocenters was accomplished by a sequential cascade of two kinetic resolutions, which features a Sharpless or Hafnium-catalyzed asymmetric epoxidation and a subsequent W-catalyzed aminolysis. Enantiopure products with up to >99.9% ee and >99.9 : 0.1 dr were obtained and could serve as potential building blocks for pharmaceutical or biological significant molecules.

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Figures

Figure 1
Figure 1
Potential synthetic targets such as pactamycin, TMC-95A, myriocin, riboflavin and coenzyme F420.
Figure 2
Figure 2
Top: Equation of krel (selectivity) as a function of ee and conversion (c), with known values of R0, and S0. (Refer to SI for derivation of equation) Bottom left: Plots of ee (product) vs. conversion when ee0 = 0 % (racemic mixture), with varying selectivity (500, 50, 20 and 10). Bottom right: Plot of ee (product) vs. conversion when ee0 = 0 % (racemic mixture) and 80 % (non-racemic), both with a selectivity of 20.
Figure 4
Figure 4
Substrate scope of the combined system of titanium-catalyzed or hafnium catalyzed asymmetric epoxidation and tungsten-catalyzed ring-opening. Letter a, b, c, d, e, f represents methods used in Table 1, for example 1ae denotes substrate 1 was subject to epoxidation by method a and ring-opening by method e. (Refer to SI for details) Yield refers to yield for each individual step, not overall yield.
Scheme 1
Scheme 1
Top: Two-step combined epoxidation/ring-opening strategy for the synthesis of aminodiols with three-stereogenic centers. Bottom: Ligands and substrates for reaction screening.
See this image and copyright information in PMC

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