Solvent-Free One-Pot Diversified Protection of Saccharide Polyols Via Regioselective Tritylations

Abstract

Regioselective installation of trityl protecting groups, widely employed in organic synthesis, was demonstrated to occur in high yields on primary positions of sugar polyols in the presence of a very limited stoichiometric amount of pyridine (ca 2 equivalents) and trityl chloride (1.1 eq) at 100 8C. Under these conditions, that can be regarded as “solvent-free” conditions because of the insolubility of the polyol substrates, reactions take remarkably shorter times than in most examples reported in the literature. In addition, the method proved applicable under air without resorting to inert atmosphere. In the second part of the paper, the scope of the present tritylation approach was significantly extended with the development of streamlined “one-pot” and fully “solvent-free” sequences allowing regioselective tritylation/alkylation (or silylation) of saccharide polyols in short times and good yields, following experimentally simple protocols

Catalytic, Regioselective Sulfonylation of Carbohydrates with Dibutyltin Oxide under Solvent-Free Conditions

“…The availability of simple solvent-free methods for the quick and high-yielding 6-Oprotection of sugars with silyl [34] and trityl groups [36] spurred us to explore the reactivity of sugar building-blocks protected at primary positions with such groups (Table 2, entries 1-5). With these less polar substrates, a lower DIPEA excess (3 equiv.)…”

“…Over the last few years, there has been a growing interest in the development of solvent-free approaches focused on synthetic carbohydrate chemistry [29], and numerous contributions were provided by our laboratory, with the proposal of non-conventional and experimentally simple procedures for the regioselective protection of sugars with benzyl [30][31][32][33], allyl [31], silyl [34,35], trityl [35,36] and acetal groups [37], and the possible sequential application thereof in one-pot procedures [34,36,38]. In this frame, the mentioned benzylation/allylation procedure [31] represented the first example at the use of catalytic dibuyltin oxide for stannylene-mediated alkylations, after about 30 years of stoichiometric applications.…”

Solvent-Free Approaches in Carbohydrate Synthetic Chemistry: Role of Catalysis in Reactivity and Selectivity

“…Recently, a solvent-free version was also developed to achieve further regioselective protective etherifications on sugars. Primary positions can be preferentially protected with bulky electrophiles, and they can be tritylated [58] or silylated [59] in the presence of a slight stoichiometric excess of pyridine (2.2-3.0 equiv., not sufficient for dissolving the polyol substrate) and the requisite trityl (Tr) or silyl chloride (in particular, tert-butyldimethylsilyl or tert-butyldiphenylsilyl chloride, namely TBDMSCl or TBDPSCl, respectively) (Scheme 9). Scheme 9.…”

“…An interesting extension in the scope of some of the above-described procedures was achieved through the development of fully solvent-free, one-pot sequential schemes allowing regioselective installation of orthogonal protecting-groups. In most cases, tin-catalyzed steps of benzylation or allylation were incorporated into such sequences, making the following sequential protections feasible: Tritylation/benzylation [58], tritylation/allylation [58], benzylation/silylation [59], and allylation/silylation [59]. A conceptually interesting further extension in the scope of these streamlined strategies was recently reported with a sequential, fully solvent-free scheme, relying on an initial regioselective alkylation (benzylation, silylation) followed by an acetalation (ketalation) step [62].…”