Synthesis, Stereostructure, and Conformations of Novel Bi- and Trifunctional (+)-Isomenthone Derivatives

Abstract

[reaction: see text] Following protection, keto alcohols 4 [from (+)-isomenthone] undergo reduction to 1,3-diol 6 (S configuration at the new stereocenter). Organometallic C-nucleophiles add to the carbonyl with the same facial selectivity as hydride, providing multifunctional derivatives, e.g., 8 and 9, with five contiguous stereocenters. The side chain hydroxyl of 4 is elaborated into amino and amide derivatives (e.g., 12). Structural analysis shows that 6, 8, 9, and the precursor to 12 (10) all adopt triaxial solid-state conformations.

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

“…318 In the case of a more substituted cyclohexanone related to menthone, additions of allylmagnesium and aryllithium reagents were also highly diastereoselective, although reaction conditions were not provided (Scheme 181). 321 The illustrated conformation of 459 could be favored, and developing 1,3diaxial interactions with the axial methyl group and the isopropyl group would develop upon addition to the axial face of this conformer. Conformational constraints imposed by other substituents on 2-alkoxycyclohexanones exert strong influences on stereoselectivity (Scheme 182).…”

Metalated Heterocycles and Their Applications in Synthetic Organic Chemistry

“…117a The lithiated species have been used frequently as nucleophiles, for example, in addition reactions to aldehydes in nucleoside chemistry, 117b,118 or to ketones in (+)-camphor, (-)-fenchone, 11 or (+)-isomenthone derivatives. 119 2-Lithiopyridine has also been used to obtain tris(2pyridyl)carbinol by addition to bis(2-pyridyl) ketone, 120 as well as bis(2-pyridyl)carbinols by reaction of 2 equiv of the organolithium with esters, 121 whereas only attack of 1 equiv of an organolithium such as 60 has been observed in the reaction with the chiral β-amino ester 59 to give the ketone 61 (Scheme 17). 67a Furthermore, there are examples of opening of cylic carbonates for the synthesis of taxoids, 73 additions to chiral tert-butylsulfinimines, 122 or the synthesis of vinylfuro[3,2-b]pyridines such as compound 64, pre-pared by iodine-lithium exchange on pyridine 62, followed by anionic cascade through a 5-exo-dig addition on the triple bond in derivative 63 (Scheme 17).…”

“…Thus, 2-lithiopyridine is obtained usually by treatment of 2-bromopyridine with n -butyllithium at low temperature, although naphthalene-catalyzed lithiation on chloropyridine has also been used 117a. The lithiated species have been used frequently as nucleophiles, for example, in addition reactions to aldehydes in nucleoside chemistry, 117b, or to ketones in (+)-camphor, (−)-fenchone, or (+)-isomenthone derivatives as well as bis(2-pyridyl)carbinols by reaction of 2 equiv of the organolithium with esters, whereas only attack of 1 equiv of an organolithium such as 60 has been observed in the reaction with the chiral β-amino ester 59 to give the ketone 61 (Scheme ) 67a…”

Phosphino-carboxamides: the inconspicuous gems

“…159 Amides 85 and 86 (Scheme 33) were prepared from the respective chiral phosphinocarboxylic acids and (À)-1-phenylethylamine and extensively tested in Pd-catalysed asymmetric allylations. 160 Related bicyclic compound (87) 161 and phosphinoamides prepared from 2-(diphenylphosphino)benzoic acid and terpenic 162 or cinchona amines 163 were also reported. Two planar-chiral phosphinoferrocene amides 88 (Scheme 34) were obtained in several steps from enantiopure ferrocenyl p-tolyl sulfoxide and applied to Cu-catalysed conjugate addition of diethyl zinc to chalcone and diethyl ethylidenemalonate (best ee's ca.…”