Investigation of a Stereoselective Co-Mediated Rearrangement Reaction (original) (raw)
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Helvetica Chimica Acta, 2012
Lately dedicated to Prof. J. Jurczak on the occasion of his 70th birthday 1 ) Treatment of cyclohexadecanone (1g; with I 2 (2.2 mol-euqiv.) and KOH in MeOH) furnished the unsaturated (Z)-ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3-chloroperbenzoic acid (m-CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone (¼ cyclopentadecanone; 1f) with NaOH in MeOH/H 2 O and then HCl at 658. This methodology was similarly extended to higher (C 17 ) and lower (C 15 to C 11 ) cyclic ketone analogues, as well as regioselectively to (À)-(R)-muscone (5c) and homomuscone (5f) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1-oxaspiro[2,n]alkanes and -alkenes 4 and 8, resulting from a CoreyÀChaykovsky oxiranylation, are also presented. Helvetica Chimica Acta -Vol. 95 (2012) 428 2012 Verlag Helvetica Chimica Acta AG, Zürich 1 ) In early 2011. For patent reasons, this manuscript (2008) was kept for several years prior to submission. 2 ) For a recent review, see [1]. 3 ) 3-(5-Isopropenyl-2-methyl-cyclopent-1-en-1-yl)-2,2-dimethylpropyl propanoate. 4 ) For a specific review, see [4]. 5 ) For supported conditions, see, e.g., [6]; for enzymatic lactonization, see, e.g., [7]; for a recent review, see [8]. Helvetica Chimica Acta -Vol. 95 (2012) 429 6 ) Treatment of the known 1,3-dioxolane-2,2-dioctanol (Ia) [16] with CBr 4 and Ph 3 P (see Scheme 3 in the Exper. Part) afforded the unreported corresponding dibromide Ib (yield 65%), which was then cyclized (Na 2 S, EtOH [17]) to the new cyclic thioether IIa (61%), prior to oxidation (H 2 O 2 , NaHCO 3 , MnSO 4 , MeCN [18]) to sulfone IIb (95%). When treated under RambergÀBäcklund conditions (KOH, Al 2 O 3 , EtOH, CCl 4 or CBr 2 F 2 , 608 [19]), this sulfone IIb afforded, in 70 -82% yield, a 3 : 7 (E)/(Z) mixture of unsaturated macrocyclic acetal III, a known precursor in the synthesis of civetone (IVa) by Stoll and co-workers [20]. Similarly, hydrolysis of acetals IIa or IIb (HCl, THF/H 2 O) furnished the corresponding macroheterocyclic ketones Va or Vb (58 -60%) respectively, both devoid of olfactive character. Acylation of Ia (AcCl, DMAP, Et 3 N, CH 2 Cl 2 ) afforded diacetate Ic (60%). Quantitative hydrolysis of acetals I to ketones VI (HCl, THF/H 2 O)
A Chelation-Controlled Ester Enolate Claisen Rearrangement
Journal of Organic Chemistry, 1995
The Ireland ester enolate Claisen rearrangement gives rise to 2-trisubstituted alkenes due to heteroatom-enforced control over the conformation of the transition state. An oxygen-bearing functional group at the tertiary carbinol center, which can coordinate to the enolate metal via a seven-membered chelated transition state, provides the control element to explain the selectivity. a$-Disubstituted unsaturated carboxylic acids are also formed with high diastereoselectivity.
beta.-Hydroxy esters: (E)- versus (Z)-enolate geometry in dianionic Claisen rearrangements
The Journal of Organic Chemistry, 1988
Control elements operative in the @hydroxy ester dianionic Claisen rearrangements are probed. Stereochemistry at C, dictates face selectivity at C, and C, in 1-2-5, but only to the extent that it controls ester enolate geometry since a second important control element, chair/boat selectivity, is also operative. Evidence for excellent Wenolate selectivity in the enolization of 0-hydroxy esters (cf. 7 and 13) and substrate-dependent chair/boat selectivity in the ensuing Claisen rearrangement are described.
The Journal of Organic Chemistry, 1989
Studies probing several aspects of a proposed yohimbane alkaloid synthetic strategy based upon the zwitterionic amino-Claisen rearrangement reactions of isoquinuclidenes have been conducted. As part of these efforts, methods have been developed to prepare 7-ketoisoquinuclidenes and their derivatives. An approach to these substances utilizing an oxidative cleavage sequence starting with 7-acetylisoquinuclidenes has been shown to be limited to C-6 electron withdrawing group substituted systems owing to an interesting rearrangement reaction which occurs upon attempts to a-oxidize enolate anions derived from these substrates. A more successful approach has been developed which employs Diels-Alder cycloaddition of the ketene equivalent, a-acetoxyacrylonitrile to N-carbethoxy-1,2-dihydropyridine followed by deprotection to liberate the 7-ketone function. Zwitterionic amino-Claisen rearrangements occurring in reactions of a series of isoquinuclidenes with alkyl propiolates have been probed, and limitations of this process have been uncovered. However, the diethoxy ketal of a 7-ketoisoquinuclidene has been shown to be efficiently converted to an enone-containing, cis-fused hydroisoquinoline upon treatment with methyl propiolate. Finally, methods for stereoselective introduction of the reserpine E ring functionality have been modeled. The strategy involves cyanosilylation of the enone function followed by hydroboration-oxidation of the regioselectively formed silyl enol ether, alcohol methylation, silyl ether deprotection, and esterification. The stereochemical aspects of these processes are discussed.
Journal of the American Chemical Society, 1978
The photochemical behavior of two chiral monocyclic enones, 4-methyl-4-phenyl-and 4-methyl-4-propyl-2-cyclohexenone. has been investigated. In both systems, it was found that the rearrangement to bicyclo[3.1 .O]hexan-2-ones (lumiketones) proceeds stereospecifically, with no loss in optical purity. The same conclusion is reached for the products of aryl migration in the former case, while the rearrangement to a 3-substituted 2-cyclopentenone in the latter case is at least 64% stereospecific. The results are consistent with synchronous mechanisms for these rearrangements describable in terms of orbital symmetry formalisms as [,2a + ,2,] and [,2, + .2,] cycloadditions, originating from triplet excited states of the reactants. Open diradical intermediates are clearly not involved in these reactants. This supports the contention of Woodward and Hoffmann that considerations of orbital symmetry can be used to predict the stereochemical course of reactions proceeding from excited states with unpaired electrons. The inefficiency in these reactions is found not to be due to reversion to starting material from diradical intermediates, but rather is a consequence of the shape of the T I and So potential surfaces in the region corresponding to twisting of the enone around the C=C bond.
A novel entry into 3-acetylcyclohexanone via a cope rearrangement
Tetrahedron Letters, 1978
We recently reported an interesting approach to a thiapyran rearrangement of [l]'(equation 1). This work prompted us to attempt with nitrogen according to the scheme delineated in equation 2. derivative [2], via replacing the pyran Various imines [3] (R = Me, Et, n-Pr, and n-Bu) were prepared by mixing a slight excess of the appropriate amine with the dimer of methylvinyl ketone in diethyl ether over molecular Cope oxygen sieves. The imines were obtained in good yield and could be purified by distillation. However, because of rapid deterioration they had to be used within a short time of purification. Passing the imines through a heated column (250' C) resulted in an efficient conversion to an enamine product (R = Me(62%); Et(58X); n-Pr(74X); n-Bu(70%))2. Spectral analyses of the products were not consistant with structure [4] (see tables 1 and 2); and, hydrolysis of the rearrangement products yielded 3-acetylcyclohexanone [713. This observation is best rationalized by the scheme presented in equation 3.