Intramolecular Oxymercuration of Stereoisomeric Cyclohexyl-Belted Poly(spirotetrahydrofuranyl) Platforms

Abstract

The four tetraspiro carbinols 28, 30, 41, and 43 and the three trispiro cyclohexenones 25, 38, and 53 have been synthesized and individually subjected to intramolecular oxymercuration. The three-dimensional structures of all 10 products have been unequivocally established by X-ray crystallographic analysis. In seven of these structures, the preferred solid-state conformation features an axially disposed C-Hg bond where the mercury atom is internally chelated in a 1,3-diaxial relationship to at least one or, more often, two oxygen centers. An unusually strong preference has been observed for equatorial occupancy on the part of the C-O bonds. This bias can be attributed to the relief of torsional strain effects that arise when gauche CH 2 ---CH 2 interactions are skirted. An important mechanistic distinction separates the kinetically preferred trans mercuricyclization of the tetraspiro alcohols from the contrasting cis stereochemical ring closure exhibited predominantly by the unsaturated ketones. In the first instance, the approach of Hg 2+ to the double bond is governed to a large extent by coordination to a proximal axially oriented ether oxygen. Where the ketones are concerned, precoordination to the Lewis basic carbonyl oxygen presumably initiates spirocyclization in a fashion controlled by the conformational preference of the resident tetrahydrofuranyl subunits.

Versatile Methodology to Hydrate Alkynes, in the Presence of a Wide Variety of Functional Groups, with Mercury(II) p-Toluensulfonamidate, Under Catalytic, Mild, and Neutral Conditions

“…Product 35 was obtained and also the dehydration product 36 as a major product (in a ratio of 1:6), due to 35 is a β-hydroxyketone that dehydrates to afford the highly conjugated α,β-unsaturated ketone hydration of the internal alkyne was observed, and a 1,5-dicarbonyl compound was obtained instead of a 1,6-diketone, which is the product expected from the usual hydration mechanism, due to the insertion of the Hg-ligand entity on the less acetylenic carbon (Scheme 2). [14], [15] The explanation for this result could be based on the fact that the hydration of the terminal alkyne is faster than that of the internal one, thus the product 38 is obtained as a reaction intermediate, then in a second step a 1,5-dicarbonyl compound 39 is formed instead of the 1,6-diketone by the anchimeric assistance of the initially formed carbonyl group, according to a mechanism previously reported [16] (Scheme 2).…”

“…Intermediate (IV) could afford the α-mercuriated carbonyl compound (V) that has been characterized by X-ray diffraction analysis in previous studies. [14] …”

Catalytic Hydration of Alkynes and Its Application in Synthesis

“…An acidmediated hydrodemercuration takes place (II → IV, maybe via III), and this step might be rate-determining, based on measured deuterium isotope effects of 5 (reaction in D 2 O with D 2 SO 4 , Hg 2 SO 4 ). 169 Curiously, a-mercuriated carbonyl compounds (Scheme 15, III), which are well characterized and for which X-ray crystal structure determinations exist, 170 have been little considered in mechanistic discussions. It is assumed that the reaction product is initially released as an enol (IV), before tautomerizing to the final product, though enols have not been directly observed.…”

Reactions of Allylmagnesium Reagents with Carbonyl Compounds and Compounds with C═N Double Bonds: Their Diastereoselectivities Generally Cannot Be Analyzed Using the Felkin–Anh and Chelation-Control Models

“…The Felkin–Anh or related models (for example, Scheme ) and the chelation-control model (for example, Scheme ) often fail to rationalize the product obtained in these transformations, although they can explain selectivities observed for additions of other organometallic nucleophiles. In some cases, allylmagnesium reagents react with opposite selectivity to other Grignard reagents − (for example, Scheme ). These problems can hinder efforts to develop stereoselective syntheses of natural products using allylmagnesium reagents, as illustrated for additions to structurally similar substrates 10 and 12 , which occur with contrasting selectivities (Scheme ).…”