Illeprinted lrom the.krurnalof Organic('hemistrl', ,14, 2;169 (1979).1 (-'opyrightO 19?9ltv the American (lhemical Society and reprinted bv permissiot-rol'the copyright owner. Slr2 Displacements and Reductive Coupling of Ketones with Olefins in N,N-Diethylacetamide and N-Ethylpyrrolidone Allan F. Sowinskiand GeorgeM. Whitesides* Departmentof Chemistrt',Massachusetts Institute of Technologt',Cambridge, Massachusetts 02139 ReceiuedMarch 8. 1979 N,l/-Diethylacetamide (DEA) and N-ethylpyrrolidone (NEP) are complementaryto hexamethylphosphoric triamide (HMPA), dimethylformamide,and dimethyl sulfoxideas solventsin which to carry out severalreactions commonly conductedin polar, aprotic media. Reactionof neopentyltosylates with lithium halidesin DEA and NEP givesgood yields of neopentylhalides. Ketonesand terminal olefinsare reductivelycoupled to tertiary, alcoholsin fair to good yields in mixtures containing NEP, sodium, and f erf -butyl alcohol;1-hepten-6-one and 1-octen-7-oneare cleanly cyclizedto five- and six-memberedrings, respectively,in good yield by this samemixture. Terminal olefins are reduced to alkanes in fair yield by DEA sodium ferf-butyl alcohol mixtures; di- and tetrasubstituted olefins are resistant to reduction bv this mixture. Hexamethylphosphorictriamide (HMPA) is a dipolar more limited value than HMPA for dissolving-metalre- aprotic solventr'2that is particularl5rvaluable for such duction of olefins. In addition, we describea useful new reactionsas SN2displacement with anionic nucleophilesrr'a reaction which occurs in NEP (but not in HMPA) bv and dissolving-metalreductions.s The routine use of which ketonesand terminal olefins are reductively coupled HMPA has beendiscouraged by the announcementthat to tertiary alcoholsby sodium-ferf-butyl alcohol mixtures. it may be carcinogenic.6In the courseof other studies, we required quantities of several neopentyl halides. Results and Discussion Compoundsof this type had proved in previouswork to Bimolecular Substitution in DEA and NEP. Table be most rapidly prepared by displacementof tosylate ion I lists the yields of alkyl halidesdetected following the by halide ion usingHMPA as solvent.:r'?A recentpaper treatment of neopentyl and cyclohexyltosylates with ca. by Young and Dewald reported that l{,.4/-diethylacetamide 2 equiv of lithium halide in varioussolvents. DEA, NBP, (DEA) and other tertiary amide solventsdissolved sodium and ly'-acetylpyrrolidine(NAcP) afford marginally higher metal and gaveblue solutionscontaining solvatedelectrons yields of neopentylchloride than HMPA and significantly and metal anions.s Young and Dewald suggestedin improvedyields comparedwith yields obtainedwith the passingthat the high sodium cation solvatingability and common dipolar aprotic solventsl/,1/-dimethylacetamide chemicalstability indicatedby this observationmight find (DMA), DMF, and Me2SO. Severalanalogues of DEA application in other types of reactions.8Here we describe listed in this table proved to be lesseffective solventsfor experimentsconfirming that DEA and l/-ethylpy'rrolidone displacementthan their parent structure. Although DEA (NEP) are comparableto HMPA as solvents for dis- is comparableto HMPA as a solvent for nucleophilic placementreactions and that they are of significant,but substitutions involving neopentyl tosylate and 2,2-di- methylpropanediyl 1,3-ditosylate,it is notably poorer than (1) For reviewsof HMPA, see: Normant,H. Angeu. Chem.,Int. Ed. HMPA for nucleophilic displacement of tosylate from Engl. 1967,6, 1046S7; Normant, H. Bull. Chim. Soc.Fr. 1968,791 826. 2,2,3,3-tetramethylbutanediyl1,4-ditosylate with lithium (2) Gutmann, Y. CHEMTECH 1977,255 63. in addition to lower yields, NEP and DEA (3) Mosher,H. S.;Stephenson,B.;Solladie, G. J. Am. Chem. Soc.1972, chloride: 94,4t84-8. appearto give products contaminatedby monohalogenated (4) Schlessinger,R. H.; Richman,J. E.; Lee C. S.; Herrmann,J. L.; materials(ca. 10-15%); DMF and Me2SOare againmuch Cregge,R. J. Tetrahedron Lett. 1973,2425 28. less effective. The practical utility of DEA as a solvent (5) Ehmann,W.J.; Whitesides,G. M. J. Org.Chem.1970,35,3565 ?; and referencescontained therein. for displacementsat neopentylcenters is indicated by the (6) Lloyd, J. W. J. Am.Ind. Hyg. Assoc.1975,36,917-9;Zapp, J. A., isolation of good yields of neopentyl chloride, 1-chloro- Jr. Science1975, 190,422 3. 2,2-diethylbutane,1,4-dibromo-2,2-dimethylpropane, and (7) Gutowski,F. D.; Whitesides,G. M. J. Org.Chem.1976,'11,2882 5. (8) Young,C. A.; Dewald,R. R. J. Chem. Soc.,Chem. Commun.1977. pentaerythrityl tetrabromide from preparative-scalere- 188 9. actions. The experimentalprocedures followed in DEA 2370 J. Org.Chem., Vol. 44, No. 14,1979 Sowinskiand Whitesides TableI. Conversionof Alkyl Tosylatesto the Corresponding Alkyl Halides by Reactionwith Lithium Halides in Various Solventsd GC yield, % solventb (CH,),- (c,H,),- [(cH..),- (cH.),- c-Co- structure abbrev CCH,CI ccH,cl ccH,clI, C(CH,Iir), C(CH,Br). H,, Cl tl iqa CH,CH,CH,CONCH"CH. NEP 89 52 JD" H cH.coN(cH,cH.), DEA 87 (69)d'n Q7)d,f 68c 101(?oyr'r (6S;a' 26 CH,(CH,),NCOCH. NAcP 83 cH.cH2coN(cH.cH.)" DEP 79 ((CH,),N).P- O HMPA 78 (62)d'i 102(85)d 702 25 ci,c9l(cx, ), DMA i 4 .>^ cHrcH,cH,coNCH. NMP 70 cH3coN(cH2cH')'NCH3 NMPA 69 HCON(CH,), DMF 61 ll (cH,),CHCON(CH,CH,), DEB 57 CH.CON(CH,CH,),O NAcM 46 CH.SOCH, MerSO 45 /1 tt cH.coN(cH(cH3)' )' DPA 37 a Unlessspecified otherwise, displacementreactions on neopentyl tosylateswere cafie(l out a1 103-1 10 (l ()!f. I i I lll pe ods by employingapproximalely 2equivof lithium halideand tosylateconcentrations oi ca-0.26llItht'srr5.rrrLrtr,rnot ryclohexyl tosylate was conducted at 68-72 C over 20-h periods by employing approximately 2 equiv ol lithrrrm rhlorirle and a tosylate concentration of ca. 0.26 M. D Abbreviations: NEP, N.ethylpyrrolidone; DEA, N.N-dielhl ltc,':.,mrrle. NAcP, N-acetylpyrrolidine; DEP, N,N'diethylpropionamide; HMPA, hexamethylphosphorictriamide: Dll.-\. \ \ ,rinr"thyl' acetamide;NMP, N-methylpyrrolidone; NMPA, N-melhyl-N -acetylpiperazine;DMF, N,N-Cimethyllof mami(:, : I )F-U. .\..\ ' diethylisobutyramideI NAcM, N-acetylrnorpholine;Me, SO, dimethyl sulfoxide; DPA, N,N-diisopropvlaccl iinli( i. ( ] clo- hexene (66-70%) was the major product from the treatment of cyclohexyl tosylate with lithiunl chlolirii' in \ rfL{'u. solvents. Material balances d ()t ()DFnlvr -Ite were 90-99%. The vield was determined bv isolation. " The concentration nt i,)\\'rf,rewas 0.3M. / substittrtionof 2,2-diethyl"bulyll-tosylate was carried out at 150-160'C overu JrJ.|lpe'r,"1 r'r ,m;,..,r rr{ 1.4 equiv of lithium chloride. s The concenlration of dilosylate was 0.14 M. h The substitution ol penlaer!ih,-Li!Lr,.lramesyl- ate $as carried out at 135-140 "C over a 48-h period by employing 1.5 equiv of lithium bromide ancllln)f"\lr,i, r(,ncentla- tion of 0,5 M. i Reference3. preparations are analogous to those employed with Table II. Reduction of Olefins to I{r'clroc'arbonsu-ith HMPA.e Products are easily isolated by dilution of the Sodium and 1r,rl-Butvl Alcohol ', reaction mixture with 1-2 volumes of water and extraction Vlr'l(1. with an immiscible solvent such as hexane. .' .r:'1 in( l' '7 Displacementreactions on cyclohexylrings generallydo reactanl solvent prodttct rn.rt,',,'ial. ) not proceedwell.lO Table I includes the yields of cy- 1-hexene HN'lPA ri-hexiine l. \ clohexyl chloride obtained from the reaction of cyclohexyl DEP i):r r I I DEB tij r19t tosylate with lithium chloride in various solvents. Cy- -..' clohexyl tosylate primarily undergoeselimination in all of DEA r.l I .il the solvents tested, giving cyclohexene(65-67 DPA r ltr I %) and NEP jrrrllt modestyields (14-33%). of cyclohexylchloride DEA and NMPA I r I., ) NEP appear to offer no special advantageto HMPA or NAcP I r(l-1t DMF as solvents for this reaction. cyclohexene HMPA c1'cloht'xane !ill, Dissolving-Metal Reduction in DEA. Dilute blue DEA lirr()) solutions are formed when DEA, NEP, and l/,l/-di- DEP Irtr-(l()t 2,3-climethvl ethylpropionamide (DEP) are stirred vigorously with telramethyl- DEA I r1U0) ethylene butatre sodium shot. In comparison,DMA is rapidly decomposed o under these conditions and HMPA gives concentrated, Reactions were carried out by vigorcluslv stirring a almost opaque,blue-black solutions. The blue solutions mixture of sodium shot (ca. 0.3 g, 13 mmol). oletin r1.2 mmol), ferf-butyl alcohol (0.3-mL (ca. formed by thesel{-ethylamides and aliquots 3 are considerablyless stable mmol) added at 6-8-h intervals) in the specified solvent than that formed by HMPA,rr and persist at room tem- (6.0 mL) at ambient temperature over 17-24-h periocls. perature only 2-3 min after removal from the metal. D Abbreviations are the same as those used in Table I. c Whereas HMPA-metal solutions are stable even to 1 equiv Reference 5. of tert-butyl alcohol, N-ethylamide-metal solutions are decolorized instantly by it. HMPA-sodium-terf-butyl tempts to improve the reducingmedium were unsuccessful. alcohol mixtures are effective for reducing nonconjugated For example,sodium -potassium alloy (78 wt % K) and alkenes and polyalkylated aromatic compounds.s We lithium, sodium,and sodium-alumina dispersionsappear attempted analogousreactions with some simple olefins, to reduce DEA12and afford only low conversionsof 1- and these results are summarizedin Table II. Terminal hexeneto n-hexane. HMPA-sodium-ferf-but.vl alcohol olefins are reducedslowly in fair yield in DEA, DEP, and mixtures are noticeablystabilized by the addition of THF N,l[-diethylisobutyramide (DEB), but multiply alkyl- as a cosolvent,although their reactivity toward reducible substituted double bonds resist reduction. Various at- substancesseems undiminished.ll The addition of THF or TMBDA to DEA as cosolventsdid not enhance the solubility of sodium or stabilizethe resultant blue solution (12)Larcheveque, M.;Cuvigny, T.;Normant, H. C. R. Hebd.Secnces Acad. Sci.,Ser. 1973,276,209 12. ReductiveCoupling of Ketoneswith Olefins J. Org. Chem., Vol. 44, No. 14, 1979 2371 Scheme I Table III.