Conjugate Addition of Methylmagnesium Iodide to 10-Methyl-1(9)-octal-2-one. An Approach to the Valeranone Carbon Framework

Marshall, James A.; Fanta, Wayne I.; Roebke, Heide

doi:10.1021/jo01342a007

Cited by 40 publications

(21 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We therefore explored the use of these reagents for the crucial introduction of an angular methyl group in the octalone 7 and found that lithium dimethylcopper, which is prepared simply by reaction or ethereal methyllithium with cuprous iodide (molar ratio 2: 1, respectively) at 0" under nitrogen, was excellent for this purpose. Thus, reaction of octalone 7 with an excess or lithium dimethylcopper in ether at 0" and under nitrogen for 2 h gave, after appropriate work-up, a 77 % yield of the desired (-k)-eremophil-11-en-3-one (12). The spectral properties of the latter were in complete agreement with the assigned structure.…”

supporting

confidence: 55%

“…Removal of the ether yielded a pale-yellow oil which, upon distillation under reduced pressure gave, in addition t o a small amount (0. (+)-Eremophil-11-en-3-one (12) and Derivatives (13,14) The following reaction was carried out under an atmosphere of dry nitrogen. To a stirring, ice-cold (0') slurry of cuprous iodide (6.0 g) in 120 ml of anhydrous ether was added, by injection from a dry syringe, 39.4 ml of 1.59 M ethereal methyllithium.…”

Section: Preparation Of Octalonementioning

confidence: 99%

“…At the outset, it appeared that this might be conveniently accomplished by use of the copper salt -catalyzed conjugate addition of methyl magnesium bromide (or iodide) to the a,P-unsaturated ketone system of 7. This type of reaction had been successfully employed (12,13) in the case of a number of 1 (9)-octal-2-ones (e.g. 8, 9, and 10) and, stereocl~emically, resulted in each case in the formation of the corresponding cis-fused decalone system.…”

mentioning

confidence: 99%

“…Having successfully introduced a methyl group at the bridgehead position of octaloile 7, it became important to determine the stereochemistry of the product (12). Although, as noted previously, the copper salt -catalyzed conjugate addition of methyl magnesium halides to various l(9)-octal-2-ones had invariably resulted in the formation of the correspondiilg cis-fused decalone derivatives, the obscmity of the mechanism of the reaction of lithium dimethylcopper with a,P-unsaturated ketones (15, 16) required that caution be used in assuming that decalone 12 should also possess cis-fused six-membered rings.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Stereoselective synthesis of (±)-eremophil-3,11-diene and related compounds. Concerning the structure of eremophilene

Piers¹,

Keziere²

1969

Can. J. Chem.

View full text Add to dashboard Cite

An efficient, stereoselective synthesis of (+)-eremophil-3,11-diene (3) is described. The key step of the synthetic sequence involves the conjugate addition of lithium dimethylcopper to the octalone 7, which produces (+)-erernophil-11-en-3-one (12) in good yield. The latter is converted, via the tosylhydrazone derivative 13, into compound 3. Comparison of 3 with eremophilene indicates that the initial structural proposal for the latter sesquiterpene is in error. Evidence is presented which demonstrates that eremophilene is correctly represented by structure 4.Canadian Journal of Chemistry, 47, 137 (1969) The biogenetically interesting (1) eremophilane class of sesquiterpenes possess the basic carbon skeleton 1. Since the isolation of eremophilone (2) by Simonsen and co-workers (3), the number of known, naturally occurring eremophilanetype sesquiterpenes has, particularly in recent years, grown rapidly.' Structurally, one of the simplest members of this class is eremophilene, a C,,H2, hydrocarbon first isolated from Petasites ofJicirzalis Moench. (5) and from P. albus (L.) Gaertn. (6). In 1964. Hochmannovh and Herout \ , (7), on the basis of nuclear magnetic resonance (n.m.r.) spectra, a fairly extensive chemical degradation, and correlation with hydroxydihydroeremophilone (2) (2), assigned structure 3 to eremophilene.In connection with an interest in developing general methods for the total synthesis of various eremophilane-type sesquiterpenes, we report in this paper an efficient and stereoselective total synthesis of racemic 3, and present evidence which invalidates the original structural proposal (7) for eremophilene. It should be immediately noted, however, that very recently, after our synthetic work had appeared in preliminary form (a), KPepinskL et al. (9) presented spectroscopic and structural evidence which also disagreed with the initial structural proposal for eremophilene (7) and, on the basis of this evidence, assigned structure 4 to this sesquiterpene.' This latter assignment has very recently been confirmed by a stereoselective total synthesis of (k)-4.3 We also present, in this paper, evidence which confirms that eremophilene is indeed correctly represented by structure 4.The starting material for our synthesis, 3-isopropenylcyclohexanone (S), was readily prepared, essentially by the procedure of House and co-workers (10). Thus, cuprous chloride -catalyzed conjugate addition of isopropenyl magnesium bromide to 2-cyclohexen-1-one gave the desired cyclohexanone derivative (5)

show abstract

supporting

confidence: 55%

Section: Preparation Of Octalonementioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Stereoselective synthesis of (±)-eremophil-3,11-diene and related compounds. Concerning the structure of eremophilene

Piers¹,

Keziere²

1969

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

“…hindrance of a attack by the axial 7a and 9a hydrogens (16) and it is to be expected that the absence of a C19 methyl group in 20 would yet further favor P over a attack. Furthermore, the reaction of the closely related enone 22 with vinylmagnesium bromide catalyzed by cupric acetate has been shown to give the 5P product 23 (17).…”

Section: Ots C3h7mentioning

confidence: 99%

Bridged-ring steroids. II. The synthesis of bridged steroids with a bicyclo[2.2.1]heptane ring A system

Yates¹,

Winnik²

1981

Can. J. Chem.

View full text Add to dashboard Cite

PETER YATES and FRANFOISE M. WINNIK. Can. J. Chem. 59, 1641 (1981).Bridged steroids with a bicyclo[2.2.l]heptane ring A system are formed on thermolysis of 5-vinyl 3-keto steroids. 5-Vinyl-Sa-cholestan-3-one (26) on being heated at 350°C in decalin gave 2a,5-(syn-methylmethano)-Sa-cholestan-3-one (27). Similar treatment of 17~-hydroxy-S-vinyl-S~-estran-3-one (21) gave 17P-hydroxy-2P,5-(syn-methylmethano)-SP-estran-3-one (M), which was also obtained by reduction of 2P,S-(syn-methylmethano)-SP-estrane-3,17-dione (31) with sodium borohydride on alumina. Compound 31 was formed as the major product on thermolysis of 5-vinyl-5P-estrane-3,17-dione (24) at 350°C, together with 5-(trans-propeny1)-A-nor-SP-estrane-3,17-dione (32). Compounds 27, 30, and 31 are considered to arise via intramolecular ene reactions of the A*-enols of compounds 26, 21, and 24, respectively. Compound 32 is postulated to be formed via an analogous reaction of the A3-enol of 24, followed by thermolysis of the resulting 3'-methyl-4~,5-dihydrocyclopropa[4,5]-5~-estrane-3,17-dione (36). Photolysis of 30 in methanol results in a-cleavage of the C2-C3 bond and the formation of a ketene-derived ester and two enal-derived oxetanes.PETER YATES et FRAN~OISE M. WINNIK. Can. J. Chem. 59, 1641 (1981). La thermolyse des vinyl-5 ceto-3 stero~des conduit a la formation de stero~des pontes portant au niveau du cycle A un bicyclo[2.2.1] heptane. Si on chauffe la vinyl-5 5a-cholestanone-3 (26) dans de la decaline a 350"C, on obtient la (methylmCthano syn)-2a,5 5a-cholestanone-3 (27). L'hydroxy-17P vinyl-5 SP-estranone-3 (211, traitee de la mime f a~o n , fournit I'hydroxy-17P (methylmethano syn)-2P,5 SP-estranone-3 (30) que I'on obtient egalement par reduction de la (methylmethano syn)-2P,S SP-estraned~one-3,17 (31) par le borohydrure de sodium sur I'alumine. Le composk 31 se forme comme le produ~t principal de la thermolyse de la Bridged steroids are of interest both because of their potential biological activity and because they can serve as substrates for the study of the effects of the constraints imposed on bridged bicyclic systems by the steroid skeleton in the course of the I reactions of such systems.We and others have previously investigated the synthesis of steroids incorporating a bicyclo-[2.2.2]octane (2, and references therein quoted) or bicyclo[3.2. ]]octane system (3). Here we are concerned with the incorporation of a bicyclo-[2.2.l]heptane system. Solo et al. have made extensive investigations of bridged ring D steroids of this type, which they synthesized by Diels-Alder addition of dienophiles to steroid 14,16-dienes (4, and earlier papers in this series). However, the only previous work to our knowledge that led to the incorporation of a bicyclo[2.2. llheptane system into a steroid ring other than ring D is that of Nazer ( 9 , who obtained compounds la and l b by treatment of 2a and 2b, respectively, with lithium (3), C2 and C5 (4), or C3 and C10 (5) (the last being possible only in the 19-nor series). Our initial approach was to a system of typ...

show abstract

Conjugate Addition Reactions of Organocopper Reagents

Posner

2011

Organic Reactions

View full text Add to dashboard Cite

Addition of an organometallic reagent to alpha,beta‐usaturated carbonyl compounds occurs in one or both of two modes: attack at the carbonyl function produces a 1,2 adduct, whereas reaction with the entire system gives a 1,4 adduct. Organoalkali metal reagents derived from unstabilized carbanions generally add across the carbonyl group, where as enolate and other stabilized anions usually undergo a Michael addition, introducing a carboalkyl group at the beta carbon. Grignard reagents normally give 1,2 adducts. The wide scope of these reagents has made conjugate addition of alkyl and aryl groups a useful reaction in organic synthesis. Copper‐promoted conjugate additions were generally effected by allowing an organomagnesium reagent and a alpha, beta‐ unsaturated carbonyl compound to react in the presence of a catalytic amount of copper salt. Studies since 1966 have shown that stoichiometric organocopper reagents in addition to their broad utility in coupling reactions with organic halides and in reaction with other substrates undergo unusually effective conjugate addition to a wide variety alpha,beta‐ unsaturated carbonyl substrates. Emphasis in this chapter is on stoichiometric organic copper reagents. Mechanism, scope, limitations, synthetic utility, and optimal conditions are considered.

show abstract

Conjugate Addition of Methylmagnesium Iodide to 10-Methyl-1(9)-octal-2-one. An Approach to the Valeranone Carbon Framework

Cited by 40 publications

References 0 publications

Stereoselective synthesis of (±)-eremophil-3,11-diene and related compounds. Concerning the structure of eremophilene

Stereoselective synthesis of (±)-eremophil-3,11-diene and related compounds. Concerning the structure of eremophilene

Bridged-ring steroids. II. The synthesis of bridged steroids with a bicyclo[2.2.1]heptane ring A system

Conjugate Addition Reactions of Organocopper Reagents

Contact Info

Product

Resources

About