Selective ring opening of silylated vinyloxiranes and reactivity of azido-alcohols

The chemoselective ring opening of silylated vinyloxiranes and of silylated epoxy alcohols by sodium azide has been studied. The reactivity of the α -silylated azido-alcohols thus synthesized has been investigated and the formation of highly functionalized products such as acyl azides, azidovinylsilanes, and silylated aldehydes has been rationalized.


Introduction
The discovery of new functionalized substrates remains an interesting challenge for organic chemists.In this respect, silylated azido-alcohols have a high degree of functionalization, and could be precursors for amino-alcohols which make efficient bidentate ligands for catalytic transformations. 1 Our group has been developing the study of the reactivity of highly functionalized molecules such as silylated vinyloxiranes towards organometallic species, 2 lithiated bases 3 and heterogeneous nucleophiles. 4These reactions have proved to be extremely stereo-and chemoselective, since the α,β-epoxy-γ,δ-unsaturated silanes 1a-c have three electrophilic centers and two acidic protons.However, the reactivity of compounds 1a-c has shown that of the two groups attached to the oxirane, the silyl group has a greater effect than the vinyl moiety.Not only do deprotonations occur preferentially in the position αto the vinyl functionality, as we previously reported, 3,4 but also nucleophilic openings of the trans-oxirane occur preferentially with scission of the C-O bond α− to the silicon atom rather than to the vinyl group. 2,4We should stress that the ring-opening of both cis-and trans-α,β-epoxy-γ,δunsaturated-silanes 1a-c, and of the silylated alcohols 2, 3, 4 (epoxy-protected or not) by moiety.Compound (Z)-trans-1a was totally recovered under the reaction conditions (entry 2), whereas compound (E)-trans-1b degraded completely (entry 3).The best yield is achieved with the substrate (E)-trans-1a which is substituted by an electron-withdrawing ester group (entry 1).
Compound cis-1c is transformed in an overall yield of 62%, including 44% of the S N 2 azido product and 18% of the diastereoselective S N 2' adduct with the E-configuration (entry 6).Degradation (entry 3) and low yield (entry 4) for phenyl derivatives trans-1b reflect the already reported high sensitivity of these compounds to acidic conditions. 7Other experimental conditions have been tested on compound 1c to improve this S N 2 reaction.Different solvents such as DMF, DMSO or CH 3 CN gave the azido-alcohol 7 in lower yields than in aqueous methanol.Various nitrogen nucleophiles such as hydrazines (N-phenyl-, N,N-dimethyl-, and unsubstituted hydrazine), trimethylsilyl azide or benzylamine did not transform compound 1c, which was recovered totally.The addition of Lewis acids was also useless.In the presence of Lewis acids (BF 3 •Et 2 O, ZnCl 2 or AlCl 3 ) trimethylsilyl azide, potassium phthalimide or benzylamine led only to the degradation of compounds trans-1a-(E-or Z-).When titanium tetra-iso-propoxide is used, transesterification products 14-(E or Z) were isolated in good yields of 95% (14-E) and 88% (14-Z) (Scheme 1).The phenyl-substituted derivatives trans-1b (E or Z) rearranged into α-silylated-β,γ-unsaturated-aldehydes 15-(E or Z) in yields depending on the nature of the Lewis acid (Scheme 1). 8oncerning the ring-opening of the silylated epoxy alcohol 2 and silylated epoxy ethers 3 and 4, the azido-alcohols 9, 10, and 11 are prepared in better yields (entries 7-9, Table 1) than the vinyl analogs 1a-c.In the case of the disilylated substrate 3 (entry 8, Table 1), the major azidoalcohol 10 is formed in 60% yield but some ring-opening occurred βto the silicon atom, yielding also the regioisomer 13 in 11% yield.This latter result indicates that not only is the regioselectivity controlled by the silicon atom linked to the oxirane, but also it is influenced by the hydroxy group, as had been reported previously by Chakraborty. 9,10However, this lack of regioselectivity could be circumvented, since direct silylation of azido-diol 9 afforded compound 10 in 91% yield.
The ring-opening of the diastereomers trans-and cis-1c by thiophenol in the presence of triethylamine in methanol occur efficiently within three hours.The S N 2 reaction is less chemoselective than with sodium azide since the two regioisomeric silylated thio-alcohols are obtained. 4i) PhSH (5 equiv.),NEt 3 (2.5 equiv.),MeOH, 60°C, 3h.

Scheme 2
In the major adduct, the silicon and the sulfur atoms are both linked to the same carbon atom.Compound trans-1c is transformed into a 6.8/1 ratio of compounds 16 and 17 in a yield of 97% whereas cis-1c gives a 3.5/1 ratio of compounds 18 and 19 in a yield of 98%.The minor thioalcohols 17 and 19 could be separated and isolated.The selectivity apparently depends on the relative configuration of the starting oxirane (Scheme 2).
Reaction of silylated oxiranes with nitrogen-and sulfur (in the case of vinyloxiranes)containing nucleophiles yields substituted alcohols, allylic or not, mainly arising from the opening of the oxirane in the position αto the silicon atom.The α-azido-alcohols listed in Table 1 were perfect substrates for Staudinger reductive cyclization into aziridines. 11However, none of these silylated azides could lead to an aziridine, and only degradation was observed.These results prompted us to investigate other aspects of the silylated azido-alcohols' reactivity, among which stands the activation of the hydroxyl group in the β-position to the silicon atom.

Reactivity of silylated α-azido-alcohols
The activation of a secondary hydroxyl group as a sulfonate ester can proceed in a basic medium by reacting the alcohol with sulfonyl chloride derivatives.Tosyl-and mesyl-chlorides reacted on compounds 10 and 11 with potassium hexamethylsilylamide to yield respectively the vinyl azides 20 (85%) and 21 (75%) arising from the formal elimination of t-butyldimethylsilanol caused by a Peterson elimination reaction (Scheme 3).Although only one diastereomer is obtained, the 13.7 Hz coupling constant of the two vinylic protons in the 1 H-NMR could not be attributed unambiguously to one configuration of the carbon-carbon double bond.However, NOE experiments have shown no effect between the vinylic protons and we could propose that the double bond has an E-configuration, indicating a syn-elimination mechanism which is classically observed for Peterson eliminations run in basic media.

Scheme 4
The preparation of the sulfonate esters from azido-alcohols 10 and 11 was tried in pyridine as the solvent.When submitting the silylated azido-alcohols 10 and 11 to mesyl chloride in pyridine we could isolate azido-vinylsilanes 22 and 23 in moderate yields of 43 and 53%, respectively (Scheme 4).In the case of the allylic benzyl ether 23, NOE irradiation experiments clearly showed a syn-relationship between the vinylic proton and the silylated substituent, which indicated that the double bond has the E-configuration.At this stage of our study, we could consider different possible dehydration mechanisms without being able to discriminate between E2, E1cb, or E1 pathways.However, we showed that the proton α-to the silicon atom is sufficiently acidic to be abstracted by pyridine.
The great reactivity of the sulfonate ester derivatives of the silylated azido-alcohols has lead us to consider forming them at low temperature and under the reaction conditions usually used for primary alcohols.Unexpectedly, the silylated azido-alcohols 10 and 11 are transformed into the α-silylated aldehydes 26 and 27, respectively, in 46 and 37% yield (Scheme 5).The formation of the aldehydes 26 and 27 could proceed via the hydrolysis either of the corresponding imines or of the α-silylated-imide anion.The latter anionic intermediates have been reported to be formed by treatment of azido compounds in basic medium.The proton could be abstracted from a carbon atom bearing the azido substituent and an electron-withdrawing group which stabilizes the negative charge.3][14] In our case, the silylated group could stabilize the negative charge α to the azido function and therefore could favor the formation of the imide anion.To investigate the importance of the azido group in this reaction, we prepared selectively the α-benzylamino-α-silylated alcohols 24 and 25 from the silylated epoxy-alcohol 2. 15 Compound 25 was submitted to triethylamine, N,N-dimethylaminopyridine and mesyl chloride (Scheme 6).The silicon-rearrangement yields the α-silylated aldehyde 26, produced similarly from the azido-alcohol 10 (Scheme 5).We can propose a mechanism (Scheme 7) implying the activation of the amino alcohol 25 into the amino-mesylate 28 followed by the spontaneous migration of the silyl group together with elimination of the mesylate anion.The subsequent characterization of benzylamine and aldehyde 26 suggests the possible hydrolysis of the unisolated imine that could be obtained by transformation of intermediate 25.
ARKAT USA, Inc.A similar mechanism can be proposed for the azido-alcohols 10 and 11, in which the transposition/elimination step could yield the diazo-imine intermediate 30 which could react with water and eliminate hydrazoic acid to lead to the α-silylated aldehyde (Scheme 7).To the best of our knowledge, this sila-pinacolic rearrangement of azido-alcohols has not previously been reported in the literature (Scheme 7).

Conclusions
We have investigated the nucleophilic ring-opening of silylated vinyloxiranes and of silylated epoxy alcohols with azide anion and conclude that the reaction is chemoselective and leads to the regioisomer in which the silicon atom and the azido group are α− to each other.The reactivity of the silylated azido-alcohols towards sulfonyl chlorides very much depends on the experimental conditions.We have shown that they can undergo Peterson elimination, dehydration, and silapinacolic rearrangement, leading respectively to acyl azides, azidovinylsilanes, and silylated aldehydes.The latter products are highly functionalized entities and are therefore interesting precursors for organic synthesis.

Experimental Section
General Procedures.RT denotes room temperature; "petroleum" is the fraction having b.p. 40-60ºC.

Scheme 8 (trans)-3-tert-Butyldimethylsilyl-2,3-epoxy-1-tert-butyldimethylsilanyloxypropane
(3)To a cooled (0°C) solution of the vinylsilane 31 (1.00 g, 3.49 mmol, 1 equiv.) in CH 2 Cl 2 (40 mL) was slowly added 7.40 g of m-CPBA (70% with water and 3-chlorobenzoic acid, 30.03 mmol, 1.5 equiv.).The reaction mixture was allowed to warm up to RT and after stirring for 2 h, 20 mL of brine was added.The organic layer was then dried over MgSO 4 and after partial evaporation of the solvent, 10 mL of pentane was added.The precipitate was then filtered off using a short pad of Celite.This operation was repeated four times to assure complete removal of the m-CPBA and the corresponding acid.The residue was then purified by flash chromatography on silica gel (petroleum/AcOEt:80/20), affording the silylated oxirane 3 as a white solid in 96% yield (1.01 g, 3.35 mmol).

Table 1 .
Ring opening of silylated oxiranes with NaN 3