Preparation of Chiral 2‐Stannyloxazolidines and First Considerations on the Transacetalisation Reaction Mechanism

Abstract

N‐Protected 2‐tributylstannyl‐1,3‐oxazolidines derived from N‐monoprotected chiral β‐amino alcohols were obtained through transacetalisation of (diethoxymethyl)tributylstannane under acidic conditions. In the case of 4‐substituted 2‐tributylstannyl‐1,3‐oxazolidines, the kinetic product of the reaction was shown to be the trans isomer whatever the nature of the protective group, while the thermodynamic product was the cis isomer in the N‐Ts series and the trans isomer in N‐CO2R compounds. Aspects of the transacetalisation reaction are discussed along with those concerning the isomerisation of the products, allowing an interpretation of the obtained results. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Diastereoselective synthesis of chiral α-aminoorganotributyltins via ring-opening of 2-tributylstannyloxazolidines

“…The first step of the reaction sequence reported in Scheme 1 was shown to occur diastereoselectively with a preference for the trans isomer in the N-CO 2 R series, a major isomer which is kinetically and thermodynamically favoured [21]. For the second step, further information is required in order to unambiguously determine if a concerted mechanism can be involved, as observed in the case of 2-stannylated 1,3-dioxanes or dioxolanes [29,30] or if the occurrence of an iminium intermediate is the general trend as already suggested in a preliminary report [27].…”

“…The formation of the iminium intermediates has been often reported in reactions involving oxazolidines and Lewis acids [33] and has also been used to explain the cis/trans isomerisation of 2-tributylstannyloxazolidines through this type of intermediates as shown in the upper part of Scheme 3 [21].…”

“…The tributyltin hydride allowing the synthesis of the tributylstannylmagnesium chloride reagent was a Crompton GmbH product while n-butyllithium was a Chemetall GmbH product. The N-Boc-(R)-phenylglycinol-derived 2-trialkylstannyloxazolidines 2 were prepared according to previously described procedures [21,27].…”

“…In our previous research programs, we have studied the preparation of 2-tributylstannyloxazolidines [21] from the easy available and storable diethoxymethyltributyltin [22,23] and pointed out that, upon treatment with n-butyllithium, N-Boc-2-tributylstannyloxazolidines derived from chiral b-amino-alcohols undergo clean transmetalation to afford 2-lithio-oxazolidines which are configurationally stable at À78°C [24][25][26][27][28]. Furthermore, preliminary experiments have shown that organocopper reagents in the presence of Lewis acids are able to open the 2-triorganostannyloxazolidines heterocycle to afford chiral a-aminoorganotins in a diastereoselective fashion [27].…”

Five-membered oxaza heterocyclic compounds on the basis of epoxides and aziridines

“…Fundamental aspects of the chemistry of dihydrooxazoles were reviews in [12,49], and some specific problems were considered in [2,3,13,15,17,[50][51][52][53][54]. Substituted 1,3-oxazolidines 3 are widely used as chiral auxiliaries in syntheses of various optically active compounds [55], for protection of 2-amino alcohols, and as medical agents [56], e.g., for the treatment of diabetes [57,58]; anticancer prodrugs doxazolidine, doxoform, and doxazolidine carbamate were also reported [59]. Known Garner's aldehyde (4) is an ideal starting material for the synthesis of many enantiomerically pure natural antibiotics [60].…”