Functionalised Monocyclic Five‐ to Seven‐Membered exo‐Glycals by Alkynol Cycloisomerisation of Hydroxy Buta‐1,3‐diynes and 1‐Haloalkynols

Abstract

Dedicated to András Lipták on the occasion of his 70th birthday Base-promoted (KOH or MeONa in MeOH, or NaH in THF) cycloisomerisation of partially benzylated, 1-substituted (R = PhÀCC, pyridin-2-yl, or Br) ald-1-ynitols leads to (Z)-configured five-, six-, and seven-membered exo-glycals. The reactivity of the ald-1-ynitols depends upon their configuration. The ald-1-ynitols were derived from 2,3,5-tri-O-benzyl-D-ribofuranose 1, and the corresponding, partially O-benzylated galactose, glucose, and mannose hemiacetals by ethynylation. The hex-1-ynitol 2 derived from 1 (61%) was transformed via the 1-phenylbuta-1,3-diyne 3 and the 1-(pyridin-2-yl)acetylene 5 into the five-membered exo-glycals 4 and 6 (in 66 and 72% yields, resp., from 2). The analoguous ethynylation of 2,3,4,6-tetra-O-benzyl-D-galactose 8 was accompanied by elimination of one benzyloxy (BnO) group to the hept-3-en-1-ynitol 9 (71%), which was transformed into the non-5-ene-1,3-diynitol 10 and further into the six-membered exo-glycal 11 (50% from 9). Addition of Me 3 SiCCH to the galactose 8 and to the gluco-and manno-analogues 16 and 24 gave epimeric mixtures of the silylated oct-1-ynitols (86% of 12L/12D 45 : 55, 94% of 17L/17D 7 : 3, and 86% of 25L/25D 55 : 45), which were separated by flash chromatography, and individually transformed into the corresponding 1-bromooct-1-ynitols. Upon treatment with NaH in THF, only the minor epimers 13L, 18D, and 26D cyclised readily to form the seven-membered hydroxy exo-glycals. They were acetylated to the more stable monoacetates 14L, 23D, and 28D (82 -89% overall yield). Under the same conditions, the epimers 13D, 18L, and 26L decomposed within 12 h mostly to polar products. The difference of reactivity was rationalised by analysing the consequences of an intramolecular C(3)OÀH ··· À OC (7) H-bond of the intermediate alkoxides on the orientation of À OÀC(7) of 13L, 18D, and 26D and its proximity to the ethynyl group.Introduction. -We have recently reported our investigations on the base-promoted alkynol cycloisomerisation of buta-1,3-diynlated and haloethynylated glycopyranosyl and -furanosyl alcohols to bicyclic exo-glycals [1]. In this paper, we describe the results of the alkynol cycloisomerisation of buta-1,3-diynlated, bromo-, and (pyridin-2-yl)ethynylated alditols to monocyclic exo-glycals of different ring size.In the course of the structure elucidation of naturally occurring oligoacetylenes, Jones et al. [2] and Bohlmann et al.[3] discovered the base-catalysed 5-exo-dig cyclisation of hydroxylated oligoacetylenes to 2-methylidene-oxolanes. This alkynol cycloisomerisation is favoured when the alkynyl group is activated, as in cumulated triple bonds, or by substitution with a 1-bromo, 1-chloro, 1-phenylchalcogeno (S or Se), or 1-(het)aryl group, and also by the proximity of the reacting groups, as in cyclic starting materials [1] [4 -6]. Activation of an isolated alkynyl group by coordination with a Lewis acid also promotes the cycloisomerisation [7]. In most cases, cyclosiomerisation resulted in (Z)-co...

One‐Pot Synthesis of Fused Tricyclic Heterocycles with Quaternary Carbon Stereocenter by Sequential Pauson–Khand Reaction and Formal [3+3] Cycloaddition

“…When using stoichiometric amounts of the classical cobalt complex [Co 2 (CO) 8 ] in the absence of CO [13] or catalytic amounts of [Co 2 (CO) 8 ] with tetramethyl thiourea in the presence of CO, [14] only an unidentified red complex was formed, in various solvent and at various temperatures, indicating that the reactivity of 2 is different with that of the corresponding 1,6-enynes.…”

“…Strategy B, on the other hand, starts from the Sonogashira [8] or Cadiot-Chodkiewicz [9] cross-coupling reaction (CCR) of readily available terminal 1, 6-enynes and 1-alkynyl bromide to give 1-ene-6,8-diynes 2 (or 1-ene-7,9-diynes), followed by the PausonKhand type reaction of 2 to give the bicyclic adduct 3. The ability to execute one-pot, sequential reactions, wherein the product of one reaction is the starting material for the next, is particularly significant.…”

“…As expected, various substituted and tethered enediynes 2 could be prepared in good yields by the Sonogashira crosscoupling reaction of the corresponding readily available terminal 1, 6-enynes 1 [12] with 1-alkynyl bromide, catalyzed by [PdA C H T U N G T R E N N U N G (PPh 3 ) 4 ] (5 mol %) and CuI (10 mol %) in the presence of base (Scheme 2). [8] Following the successful synthesis of 2, we screened the reaction conditions for the formal [2+2+1] cycloaddition reaction using enediyne 2 a as the standard substrate. The results are summarized in Table 1.…”

A Pd-mediated intramolecular ketalization of alkynediols: construction of the central [3.2.1]-bicyclic ketal core of cyclodidemniserinol trisulfate

“…15 Although there was a scope for 6-endo-cyclizaton with both the substrates 3 and 4, the exclusive formation of 5-exo-cyclization product indicates a dominant acyclic stereocontrol over the regiochemistry of this cycloisomerization reaction. 16 As the above strategy led to the products resulting from the undesired 5-exo-cyclization, we revised the strategy by choosing the diol 17 that has an extra carbon in between the alkyne and the next chiral centre. The competition is now between 6-exodig and 7-endo-dig, the latter being energetically more demanding.…”

Synthesis of α‐Diazo Carbonyl Compounds with the Shelf‐Stable Diazo Transfer Reagent Nonafluorobutanesulfonyl Azide

“…Thus, the synthesis of 2k using TfN 3 [20e] and of 2l using benzotriazol-1-ylsulfonyl azide [23] required in both cases a reaction time of 14 h. Imidazole-1-sulfonyl azide, which is considered as a stable and inexpensive alternative to TfN 3 , failed to give any diazo product with (phenylsulfonyl)acetates. [21] The method is also applicable to the preparation of the Ohira-Bestmann reagent [38] 2m in very high yield (Table 2, entry 13) and again in shorter reaction times than with other diazo transfer reagents such as p-toluenesulfonyl azide (2 h), [39] 4-acetamidobenzenesulfonyl azide (48 h), [40] or 2-azido-1,3-dimethylimidazolinium chloride (1 hour). [22] However, when we carried out the reaction with anitro carbonyl compounds low yields of the desired anitro-a-diazo carbonyl derivatives were obtained ( Table 2, entries 14 and 15).…”