Cuprates, addition to enones

Tab. 6.2. HMPT = Results of diastereoselective cuprate additions to enone hexamethylphosphoric triamide). 95 (TMS = trimethylsilyl,...

An asymmetric total synthesis of the alkaloid dendroba-tid 251 F 192 using a Noyori-type three-component reaction was described by Aube and coworkers (Scheme 6.26) [55]. 1,4-Cuprate addition to enone 189 is achieved from the exo-face, and subsequent aldol condensation results in the formation of only one diastereoisomer 191 in 65% yield. Dendrobatid 251 F 192 is achieved in only six further steps. 

Tricyclic templates such as 246 have been used to obtain stereocontrol in the synthesis of important cyclopentanoic natural products [85]. Normally, the endo-face of a cage-like structure is strongly shielded, and all kinds of additions occur from the exo-side. Thus, cuprate addition to enone 246 selectively gives the exoadduct 247. If, however, an additional substituent is introduced onto the exo-face as in the ether 246b or the sulfide 246c, considerable amounts of the endo-adduct 248 are generated. For X= SPH, the endo-selectivity is completely reversed, yielding exclusively compound 248. 

A number of reports have appeared which deal specifically with the creation of the AB portion of the trichothecene skeleton. The majority of this work, as shown in Scheme 7, concerns itself with alternative Diels-Alder strategies for the construction of the A ring. When methyl coumalate (120) is used as the dienophile the AB system results immediately, although a number of manipulations are needed to convert the Diels-Alder adducts to useful synthetic intermediates. In this fashion Tatsuno and Nakahara (707) have intercepted a previous intermediate (121) in their 12,13-epoxytrichothec-9-ene (1) synthesis (see Scheme 5), while Kraus and Frazier (97) have prepared ketone (122), an olefin isomer of the calonectrin intermediate (115) (see Scheme 6). Most recently, Banks and co-workers (72) have prepared lactone (124) from the Diels-Alder adduct (123). Scheme 8 summarizes some early work from Goldsmith s laboratory (57) in which the cis fusion of the AB system was generated from a cuprate addition to enone (125). 

Sdieine 6.12. Diactereocelective cuprate addition to 2 enone 61 - Ice/ ctep towardc the cynthecic of ico[7]-levnglandin D . TBS = t-biityidimethylcilyl)... 

Sdieire 6.20. Diactereocelective cuprate addition to cteroidal enone 95 (MOM = methoKymethyl). 

The poor diasteroselectivity at the yS-carbon of cyclic enones arises from poor facial selectivity during cuprate addition. Acyclic enones may also give poor dia-stereoselectivity at the y8-carbon center because of E Z isomerization arising from an equilibrium between an enone-cuprate d-re complex and starting materials. Much work remains to be done in the development of asymmetric variations in a-aminoalkylcuprate chemistry. 

Scheme 6.12. Diastereoselective cuprate addition to Z enone 61 - key step towards the synthesis of iso[7]-levuglandin D2. (TBS = t-butyidimethylsilyl)...

Scheme 6.20. Diastereoselective cuprate addition to steroidal enone 95 (MOM = methoxymethyl).

Ar= Ph, p-MePh, o-MePh R = allyl, Me, Ph, cyclopropyl, n-butyl Scheme 6.28. Diastereoselective cuprate addition to a planar chiral a lchromium enone complex 145. 

Scheme 6.29. Diastereoselective cuprate addition to chiral molybdenum Ti-allyl enone complex 147.

ESR and CIDNP studies intended to detect the radical intermediates failed [63], Conjugate addition of a vinylcuprate reagent to an enone takes place with retention of the vinyl geometry indicating that no vinyl radical intermediate is involved [64, 65], Kinetic isotope effects and substituent effects in cuprate addition to benzophenone indicate that C-C bond formation is rate-determining, which is not consistent with the involvement of a radical ion pair intermediate [66]. 

For 1,4 addition to enones, the cuprates of the bislactim ethers have been found to be very useful [88AG(E)1194]. These are made by reacting the lithio derivatives with CuBr SMe2 in the presence of dimethyl sulfide. 

ArSCu(RMgX)n. These heterocuprates are more useful than lithium dialkyl-cuprates for conjugate addition to enones.5 They are also useful for conjugate addition to the less reactive cinnamates and crotonates.6 Yields are markedly improved by use of 2-methoxyphenylthio as the ligand in additions to the crotonates. 

Mixed homocuprates.7 Mixed cuprates (1) in which the nontransferable ligand is an a-sulfonyl carbanion are easily prepared from dimethyl sulfone or methyl phenyl sulfone (equation I), and are effective for conjugate addition to enones and for a synthesis of ketones from acid chlorides. 

The methyl group at C-2 was introduced by cuprate addition to the enone 11 on the face opposite the large TBDMS group and the lithium enolate 12 trapped with Me3SiCl to give 13. This silyl enol ether was ozonised, reduced, and the silyl group hydrolysed whereupon oxidation gave spontaneous lactonisation to 1 in 12% yield from 11. 

Cossy and co-workers reported the synthesis of a variety of 3-oxacycloalkenes via RCM <02TL7263> (Scheme 37). Further transformations of these compounds, such as oi-oxyalkylation and cuprate addition to the enone were also reported. 

Recently, the direct transformation of allyl- 206272 and aryl tellurides 209273 into the corresponding organocopper species 207 and 210 by tellurium-copper exchange was described. The resulting allyl 207 or aryl cuprates 210 were captured by coupling with vinyl triflates 208272 or by 1,4-addition to enones 211,273 respectively (Scheme 112). 

Chloro-l-lithio- -pentene, CH2=C(Li)CH2CH2CH2Cl (I)." Both the Grignard and the cuprate reagents derived from 2 undergo conjugate addition to enones in moderate yield. In some cases use of BF, etherate as catalyst improves yields significantly. The products are cyclized by base to annelated methylenecyclohexanes. Overall yields vary from 40 to 70%. 

Cuprates of this type also undergo addition to enones in high yield (equation I). They should be particularly useful for effecting complete utilization of an organolithium reagent. 

Lithium phenyltkio trimethyhtannyl)cuprate, C6H5S[(CH3)3Sn]CuLi (1)/ The deep red cuprate is prepared by reaction of C6H5SCU with (CH3)3SnLi in THF at - 20°. It converts /3 -iodo enones efficiently into p -trimethylstannyl-o, j3-enones. It is somewhat less efficient than (CH3)3SnLi for conjugate addition to enones. Examples ... 

Scheme 6.28. Diastereoselective cuprate addition to a planar chiral arylchromium enone complex 145.

The organocopper reagents used for conjugate additions to enones are homocuprates, heterocuprates, higher-order cuprates, and Grignard reagents in the presence of catalytic amounts of copper salts (CuX). 

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