Indium Trichloride Mediated Cleavage of Acetonides in the Presence of Acid-Labile Functional Groups - Enhancing the Synthetic Utility of 1,3-Dioxolanyl-Substituted 1,2-Oxazines

Abstract

Indium trichloride in an acetonitrile-water mixture chemoselectively cleaved the isopropylidene acetals of various 1,3-dioxolanyl-substituted 1,2-oxazines as well as carbohydrate derivatives. Deprotection of acetonides can be achieved in substrates susceptible for acid-induced cyclizations. Most importantly, enol ether moieties are not attacked and the presence of glycosidic linkages or acid-sensitive protecting groups such as tert-butyldimethylsilyl, 2-(trimethylsilyl)ethyl, or tert-butoxycarbonyl is also tolerated.

deprotection - 1,2-oxazines - isopropylidene acetals - Lewis acids - indium trichloride

References and Notes

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8a Indium trichloride in hot MeOH has already been reported as catalyst for the selective hydrolysis of more labile acetonides: Mahalingam SM. Aidhen IS. Z. Naturforsch., B  2005,  60:  962 

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9

Typical Procedure for the InCl ₃ -Mediated Hydrolysis of Isopropylidene Acetals - Conversion of syn -1 into syn -4
1,2-Oxazine syn-1 (6.00 g, 15.3 mmol), InCl₃ (6.68 g, 30.6 mmol), and H₂O (1.10 mL, 61.2 mmol) were dissolved in MeCN (230 mL), and the mixture was stirred for 3 h at r.t. After addition of H₂O and CH₂Cl₂ the layers were separated and the aqueous layer was extracted 2 times with CH₂Cl₂. The combined organic layers were dried with MgSO₄, filtered, and concentrated. Column chromatography (silica gel, EtOAc-hexane = 1:4) provided 4.50 g (84%) syn-4 as colorless oil.
Analytical Data for (1′ S ,3 S )-1-{-2-Benzyl-4-(2-trimethyl-silylethoxy)-3,6-dihydro-2 H [1,2]oxazin-3-yl}ethan-1,2-diol [α]_D ^²² +43.6 (c 0.81, CHCl₃). ^¹H NMR (500 MHz, CDCl₃): δ = 0.04 (s, 9 H, SiMe₃), 0.96-1.10 (m, 2 H, CH₂Si), 2.84 (s, 1 H, OH), 3.04 (dd, J = 6.6, 1.6 Hz, 1 H, 3-H), 3.59 (s, 1 H, OH), 3.63 (dd, J = 11.8, 4.7 Hz, 1 H, 2′-H), 3.74 (dd, J = 11.8, 3.6 Hz, 1 H, 2′-H), 3.78-3.83 (m, 1 H, OCH₂), 3.86-3.90 (m, 2 H, OCH₂, 1′-H), 3.93 (d, J = 13.2 Hz, 1 H, NCH₂), 4.17 (dd, J = 15.3, 3.6 Hz, 1 H, 6-H), 4.20 (d, J = 13.2 Hz, 1 H, NCH₂), 4.47 (dt, J = 15.3, 1.9 Hz, 1 H,
6-H), 4.81 (dd, J = 3.6, 1.9 Hz, 1 H, 5-H), 7.24-7.37 (m, 5 H, Ph) ppm. ^¹³C NMR (126 MHz, CDCl₃): δ = -1.3 (q, SiMe₃), 17.5 (t, CH₂Si), 56.9 (t, NCH₂), 60.5 (t, C-6), 62.2 (d, C-3), 64.4 (t, C-2′), 64.5 (t, OCH₂), 72.0 (d, C-1′), 91.7 (d, C-5), 127.8, 128.4, 129.0, 136.3 (3 d, s, Ph), 148.4 (s, C-4) ppm. IR (film): 3460 (OH), 3090-2840 (=C-H, C-H), 1680 (C=C) cm^-¹. ESI-TOF: m/z calcd for [M + H]⁺: 352.1939; found: 352.2002. Anal. Calcd for C₁₈H₂₉NO₄Si (351.5): C, 61.50; H, 8.32; N, 3.98. Found: C, 61.37; H, 8.49; N, 4.12.

10

Using catalytic amounts (20 mol%) of InCl₃ gave almost no conversion.

11

Treatment of 1,2-oxazine 11 with SnCl₄ leads to bicyclic oxocanes (ref. 7) whereas protic acids promote cyclization into bicyclic tetrahydropyrans (ref. 5).

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