Umpolung carbonyls enable direct allylation and olefination of carbohydrates

Abstract

Mother Nature has its own arts to build a vast number of carbohydrates; however, there is still a lack of tools for selective functionalization of native carbohydrates through C─C bond formation. Such a long-standing challenge for the synthetic community lies into the intrinsic problems related to the innate properties of carbohydrates, e.g., the ease to oligomerization or polymerization, the difficulty of chemoselectivity control in the presence of multiple hydroxyl groups, the great challenge to retain the multiple chiral centers during the transformation, etc. Here, by applying an umpolung strategy of carbohydrate carbonyls, we report a direct deoxygenative allylation and olefination of carbohydrates to tackle the abovementioned issues. The reaction is compatible with a wide range of natural carbohydrates, providing a direct synthetic method to use carbohydrates as multiple C-centered chiral synthons to achieve C─C bond cross-coupling reactions. Furthermore, the synthetic applicability is demonstrated by late-stage modifications of natural products and pharmaceutical derivatives.

Metal–Metal BondUmpolungin Heterometallic Extended Metal Atom Chains

“… 12 − 16 For example, the modern lexicon of coordination chemistry now contains X-, L-, or Z-type ligands, which indirectly describes the polarity of a metal–ligand bond by identifying the donor and acceptor involved in the interaction. 17 − 19 Reversal of expected bond polarity, or umpolung , is also an important concept with impacts in organic synthesis, 20 − 27 catalysis, 6 , 28 − 32 frustrated Lewis pairs, 33 , 34 and bonding in main group chemistry. 35 − 37 Another area in which bond polarity plays an important but underappreciated role is in coordination compounds containing heterometallic metal–metal bonds.…”

“…Bond polarity is a fundamental property of chemical systems, with donor–acceptor interactions at the heart of acid–base reactions, − organic chemistry, , inorganic solid state chemistry, − and coordination chemistry. − For example, the modern lexicon of coordination chemistry now contains X-, L-, or Z-type ligands, which indirectly describes the polarity of a metal–ligand bond by identifying the donor and acceptor involved in the interaction. − Reversal of expected bond polarity, or umpolung , is also an important concept with impacts in organic synthesis, − catalysis, ,− frustrated Lewis pairs, , and bonding in main group chemistry. − Another area in which bond polarity plays an important but underappreciated role is in coordination compounds containing heterometallic metal–metal bonds. The recent explosion of interest in heterometallic compounds − has produced a number of systematic series that illustrate how polarity impacts heterometallic bonding generally.…”

Asymmetric addition of hydrazones as alkyl carbanion equivalents with aryl imines in water

“…Recently, inspired by the Wolff–Kishner reduction in which a carbanion was generated through hydrazone, metal catalyzed “umpolung” chemistry of hydrazones as alkyl carbanion equivalents has attracted much attention in organic synthesis and been widely applied in various addition and cross coupling reactions to construct C–C/O/N bonds. 5 As organometallic surrogates, the umpolung nucleophilic additions of non-substituted hydrazones with imines 5 b , e and other electrophiles exhibit green and sustainable characteristics with no waste metal salts or halides and with only nitrogen as the sole byproduct (Scheme 1B). 6,7 Moreover, hydrazones derived from aldehydes and ketones are easily available and moisture/air-stable.…”

Site-Selective Dehydroxy-Chlorination of Secondary Alcohols in Unprotected Glycosides

“…In our search for such a strategy, we realized that hydrazones, readily available from ketones, can react both as electrophiles and nucleophiles, 28 , 29 and can be used to functionalize unprotected carbohydrates. 30 Baldwin et al. demonstrated that lithiated trityl hydrazones act as 1,2-diazaallyl anions and add to aldehydes.…”

“…In our search for such a strategy, we realized that hydrazones, readily available from ketones, can react both as electrophiles and nucleophiles, 28,29 and can be used to functionalize unprotected carbohydrates. 30 Baldwin et al demonstrated that lithiated trityl hydrazones act as 1,2diazaallyl anions and add to aldehydes. The resulting unstable azo-intermediate decomposes at room temperature in a carbon-centered radical that undergoes hydrogen atom transfer in the presence of a thiol (Figure 1A).…”