A new approach to the stereospecific total synthesis of racemic Cecropia juvenile hormone
01 Jan 1972-Journal of The Chemical Society, Chemical Communications (The Royal Society of Chemistry)-Iss: 23, pp 1311-1312
TL;DR: In this paper, the synthesis of C18-juvenil hormone was studied using 4.4-Methyl-5,6-dihydro-2H-thiopyran and its dimer.
Abstract: 4-Methyl-5,6-dihydro-2H-thiopyran and its dimer (4) are used as structural units for the synthesis of C18-juvenil hormone.
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TL;DR: A new anionic cascade that provides convergent access to thiopyran products in a single pot from simple starting materials is reported, which would be initiated upon addition of a vinyl nucleophile to the carbonyl group, at which point the substitutent on sulfur migrates to the newly formed alkoxide, thus forming a new leaving group and a thiolate nucleophile.
Abstract: Sulfur is the fifth most important element, following carbon, hydrogen, oxygen, and nitrogen, in the context of biological significance and representation in important natural and nonnatural constructs. Its unique properties also make it one of the most chemically versatile of the early elements. For example, sulfur compounds are: 1) great nucleophiles; 2) readily reduced and oxidized; 3) good at stabilizing carbanions and carbocations; 4) a source of useful ylide and umpolung chemistry; 5) of great utility in radical chemistry; 6) able to be chiral at sulfur; 7) found in the cores of important chiral auxiliaries, and 8) the key enabling element for more than twenty name reactions in organic chemistry. In terms of pharmaceuticals, sulfur is solidly the most significant and successful element following the four key elements of life (C, H, N, and O), with seven of the ten bestselling pharmaceuticals worldwide containing sulfur. As a part of our program focused on the development of new useful synthetic transformations involving sulfur as the central element, we report a new anionic cascade that provides convergent access to thiopyran products in a single pot from simple starting materials (Scheme 1). The inspiration for the design of this new reaction originated from a desire to extend our ring expansion investigations to include vinyl thietanes, which we envisioned could be converted into a thiopyran upon treatment with a metal catalyst. Intrigued by the simple and convergent thiirane synthetic approach we had utilized for our formal synthesis of biotin, we postulated that the thiopyran constructs could possibly be accessed in a single step from an appropriately functionalized carbonyl construct containing a thiol group at the b position instead of a ring expansion path. This new one-pot anionic cascade would be initiated upon addition of a vinyl nucleophile to the carbonyl group, at which point the substitutent on sulfur migrates to the newly formed alkoxide, thus forming a new leaving group and a thiolate nucleophile. Ketones and esters were expected to be the most suitable substrates for this new anionic cascade. Tertiary substitution of the alkoxide, formed by coupling the two carbon fragments together, was expected to ensure preference for the desired 6-endo cyclization pathway over the competing 4-exo pathway. The most critical part of the reaction design was the nature of the thiol substitutent (XYZ; Scheme 1). A suitable substitutent would be required to 1) survive the addition of the carbon nucleophile, 2) readily transfer from sulfur to the alkoxide, and 3) transform the alkoxide into a good leaving group. Literature precedents suggested three structural frameworks that might fit our criteria: 1) thiocarbonateor xanthate-type acyl groups, 2) thio-substituted heterocycles, or 3) phosphates. Phosphates were chosen as the group to study the feasibility of the anionic cascade because of their ease of substrate synthesis, stability toward carbon nucleophiles, and leaving group ability (Z = P, Y= OR and X = O or S; Scheme 1). To test our hypothesis, we chose to explore the addition of vinyl nucleophiles to the aryl ketone thiophosphate 1 (Table 1). The addition product would afford a tertiary alkoxide, which would then undergo a migration of the thiophosphate to form a thiolate nucleophile, which we expected would favor the 6-endo cyclization pathway. Vinyl Grignard addition to the aryl ketone 1 proceeded well to form 2 without interference from the thiophosphate group. Interestingly, in tetrahydrofuran with magnesium as the alkoxide counterion, the expected in situ anionic cascade to form 3 or 4 did not take place. Instead, the corresponding alcohol was isolated (entry 1). Presumably the magnesium counterion impedes thiophosphate transfer to the alkoxide. However, treatment of the corresponding alcohol with an alkoxide base or sodium hydride resulted in a facile cyclization, which afforded the thiopyran 3 as the major product following an acidic workup. We postulated that an alkali metal alkoxide additive might exchange out the magnesium in situ and allow the proposed anionic cascade to proceed in one pot (Table 1, entries 2–13). After screening lithium, sodium, and potassium alkoxides in methanol, ethanol, 2-propanol, or tertbutanol, it became clear that adding potassium tert-butoxide Scheme 1. One-pot anionic cascade route to thiopyrans.
18 citations
TL;DR: Early applications of the Wittig-Still rearrangement to modifications of steroids are reviewed as are applications to various terpene and alkaloid natural product targets and miscellaneous compounds.
Abstract: This Review traces the discovery of the Wittig-Still rearrangement and its applications in organic synthesis. Its relationship to Wittig rearrangements is discussed along with detailed analysis of E/Z- and diastereoselectivity. Modifications of the products arising from the Wittig-Still rearrangement are reviewed in the context of increased complexity in intermediates potentially useful in target-oriented synthesis. Early applications of the Wittig-Still rearrangement to modifications of steroids are reviewed as are applications to various terpene and alkaloid natural product targets and miscellaneous compounds. To the best of our knowledge, the literature is covered through December 2016.
16 citations
TL;DR: L'etude physiologique des corpora allata (CA) n'apparaIit pas totalement satisfaisante tant que l'on n'a pas envisagee l'action de l'hormone juvenile sur l'Insecte.
Abstract: L'etude physiologique des corpora allata (CA) n'apparaIit pas totalement satisfaisante tant que l'on n'a pas envisagee l'action de l'hormone juvenile sur l'Insecte.
7 citations
TL;DR: A number of analogs of 2 E, 4 E )-3,7,11-trimethyl-2,4-dodecadienoate were prepared and bioassayed for juvenile hormone activity on the yellow-fever mosquito ( Aedes aegypti), the greater wax moth ( Galleria mellonella), the yellow mealworm ( Tenebrio molitor), the house fly ( Musca domestica), and the tobacco budworm ( Heliothis virescens).
6 citations