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Home , Isobutyric acid, Tetramethylbutane

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 ;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 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. Intermolecular Reductive Coupling of ooH Carbonyl Groups with Olefins in NEPa e- ncH-cHz ll | + -,^- | -ltEt RoH Corbony I hodJc t Corbonyl: GLC Yield cHr- cH 'c 2 3cNEt2 Cmod. Olefin Rot;o OH n tl o I rHl tl c il t'l 52 CHa-I -C-CH2CHR _* + cH3-c-cH2cH2R ROH 2l zs [rs-ss]d 5% t2 5l NEt2 OH OH I nu--Lr2 | Ho CH3CCH2CH2R v5 Ail I 55- I .< cH2cH2R

llr t lrnt' t- f' Ho a} t,l 65 OH OH ao 2'l 8l I I I CH3CHCH2CH2R CH3-C(CH2CH2R)2 d_' t,? 63 57o I0-20vo = e + ROH or RH [H'] 5I' toward tert-butyl alcohol; poor conversionsof terminal d_ olefin to reduced resulted from use of these mixed solvents. Attempts to employ proton donors less (e.g., acidic than tert-butyl alcohol n-propylamine, il xo\A ethylenediamine,morpholine) gave low yields of n-hexane tl

trr.r-t-)- from l-hexene. The incremental t addition of alcoholto blue 2l DEA-sodium-1-hexenemixtures alsoproduced low yields d_' of n-hexane. Our qualitative observationsindicate that the dissolution of sodium in HMPA, liquid ammonia, and ethylenedi- tl '? ir-, amine is considerablymore facile than in l/-ethylamide .<1(| <5 solvents and that HMPA is superior for the dissolving- I metal reductions of olefins to saturated . Reductive Coupling of Ketones with Olefins in NEP. Examination of the side products formed during reduction of l-hexene to n-hexane in DEA sodium- tl /^ ri'-\ "oA ll ttltl l,l terf-butyl alcohol mixtures revealedsmall amounts of llr/ k) chain-extendedproducts such as 2-octanone(ca. 5To), tl ?'l 62 2-octanol (35%), and 7-methyl-7-tridecanol(10-20%) t,? 59 (SchemeI). products These and related incorporating o solventmoieties from DEA or other solventsmake up the tl xo r.\ major part of the massbalance not reportedas n-hexane a\ t'l 4? II ) or l-hexenein Table I. The C8 and C14 productsobserved ,4, 2l 54 in DEA are probably produced by the addition of a-aminol (-/ t,? 40 and a-hydroxy radicals(or DEA and 2-octanoneradical anions)to the terminal carbonof 1-hexene.The reduction of theseintermediate radicals to saturatedproducts can xoA then occur either by single-electronreduction and pro- ') t,l tl tonation or by hydrogenatom abstractionfrom the solvent. y< The addition of a-hydroxy radicalsgenerated from primary or secondaryalcohols under free-radical conditions to o HO | | terminal olefins is well-known,lirbut a-aminol additions tl t'l g" have not been reported. Developmentof this reaction t\N'/ Y2 3,1 t8 establishedthat moderateto good yields of tertiary al- I coholscould be preparedby reductivecoupling of ketones and terminal alkeneson a small scale(1-5 mmol) in NBP, but other types of carbonyl compounds(e.g., , , aldehydes)did not result in significantyields of coupled products. Representativereactions are summarizedin Table III. In a typical example,1 equiv of 2-heptanone and excessfert-butyl alcoholwere added in portions to a vigorouslystirred 1-hexenesodium-NEP mixture at 25

(13) Sosnovsky,G. "Free Radical Reactionsin Preparative Organic Chemistry";Macmillan: New York, N.Y., 1964;pp121 5:and references included therein. 2372 J. Org. Chem.,Vol. 44, No. 14, 1979 Sowinskiand Whitesides oC over a 1-h period. The mixture was worked up by coupled product), but the geminally disubstituted olefin cautiously quenching the supernatant solution with an 2-methyl-1-penteneunderwent addition poorly (20Vo),and equal volume of water and extracting with pentane; the vicinal di- and trisubstituted olefins gave only traces extract was found to contain n-hexane(5%), l-hexene (<5%) of coupledproducts. (17Vo), 2-heptanol (16%), and 6-methyl-6-dodecanol Extension of the reductive addition reaction to other (66%). Employing a two- or threefold excessof 2-hep- carbonyl compounds was not successful. Heptanal and tanone increasedthe yield of coupledproduct to 75-8lTo, other aldehydescontaining a protons appearedto suffer based on the Iimiting reactant l-hexene; using an excess base-catalyzedcondensation before reduction took place; of l-hexene with various ketonesgenerally did not improve pivaldehyde,which doesnot bear a protons, did undergo the yield over that of the 1:1 stoichiometry. The pro- reduction to neopentanol but afforded only traces of portion of ketone reduction to alcohol and reductive coupledproduct with l-hexene ((5%). The addition of coupling with l-hexene dependson the solventused: the anhydrous formaldehyde to 1-hexenein an NEP-sodi- reduction of 2-heptanoneand l-hexene in liquid ammo- um-ferf-butyl alcohol mixture did not produce l-heptanol nia-ether affords no 6-methyl-6-dodecanol(

Table IV. Intramolecular Reductive Coupling of Scheme II Ketoolefins in NEPd o O_ OH OH ll e I no,r I lr.l I .'+\ 4-r # I I oH oH oH rR //// }{-Lr + \(Lr t.. VL \2 lLH.l I <5 <5 OH ll

tl\

[H'] = e- + ROH or RH oH oH oH aprotic conditions (anhydrousDMF-tetraethylammonium \2 p-toluenesulfonate).17Thus either reactive speciesis kfd\f\------>'--l capableof facile olefin addition, and it is not possibleto 65 <3 distinguish which is involved in reductive coupling in sodium-ferf-butyl alcohol-NEP mixtures on this basis. A mechanisminvolving the addition of olefin radical anions or sodium alkyls to the ketone carbonyl in reductive oH oH oH coupling by NEP-sodium-tert-butyl alcohol does not appear probable. The reduction of terminal olefins by l/-ethylamide-sodium-fert-butyl alcohol mixtures pro- LY tfds ceedsto 50Tocompletion after 5-10 h, and olefins do not visibly react with blue l[-ethylamide-sodium solutions. In contrast,ketones instantly decolorizethese blue solutions, 80

o in the presenceof sodium and tert-butyl alcohol (Scheme The ketoolefin (2"0 mmol) wos ollowed io reoci with viqorously stirred sodim shoi II). Reductionsof olefins to hydrocarbonscan also be ondteri-buhvr orcohor (1'B mL' e mmor) inNEP (6 l mL) accomplishedby thesesolvents in the absenceof ketones, F;1"1i;"i1#J::'' but this reactionis unlikely to prove useful in synthesis in other than unusual circumstances. and 2-nonanol (520%) and intermolecular coupling Several characteristicsof the interesting reductive products presumablycompleted the material balance. couplingreaction deserve brief comment. First, DEA and Somesuggestions about the essentialmechanistic fea- NEP are considerablymore stabletoward dissolvedsodium tures of the reductivecoupling of ketoneswith terminal than dimethylformamide, dimethylacetamide,and ly'- olefins can be drawn from these observations. The C-C methylpyrrolidone. The relativelylow stability of DMF bond-forming step probably involves the addition of the in the presenceof strong basesis well-knownand seems intermediate ketyl radical anion or a-hydroxy radical to be a result of rapid base-catalyzeddecarbonylation. The derived from one-electronreduction of the ketone to the mechanisticorigin of the difference in stability between exo carbon of the terminal olefinl3'l8(Scheme II). This (di)nrethylamidesand (di)ethylamides(and higher (di)- intermediatealkyl radical could undergosubsequent re- alkylamides)is not presently clear but is important in duction by single-electrontransfer and protonation or by choosingamide-containing solvents for these strongly hydrogen atom abstraction from any one of severalgood reducing reactions. Second,it is unclear whether the hydrogen donors that are present. The ketyl anion or reductive coupling reaction occursat the sodium surface a-hydroxy radical that does not add appearsto suffer or in solution. DEA and NEP do dissolvesodium and give reduction to the secondaryalcohol by these same se- blue solutions,but reaction mixtures are colorlessduring quences. Examplesof C-C bond formation by the addition the reductivecoupling reaction. Further, HMPA forms of either reactiveintermediate to a terminal olefin have much more concentratedsolutions of sodium than do DEA appeared. Generatinga-hydroxy radicalsfrom primary and NEP, but only the latter solventsyield the tertiary or secondaryalcohols and initiators in the presenceof alcoholsderived from reductive coupling: in HMPA, terminal olefins gives preparatively useful yields of the reduction of ketone to alcohol is the only important re- coupled product.l:r The eiectrochemicalreductive cycli- action. Although this differencemight simply reflect the zation of 1-octen-7-onegives comparableyields of 1,2- partitioning of an intermediate ketyl or protonated ketyl dimethylcyclohexanolunder protic (1:9(v/v) methanol/ betweenaddition to olefin and reductionto alcohol(ate), dioxane-tetraethylammonium p-toluenesulfonate) or it may also indicate some more major difference in 2374 J. Org.Chem., VoL 44, No. 14,1979 Sowinski and Whitesides mechanism. Third, in a practical sense,this reaction is (CDCI3)6 3.60 (8 H, broadened.split s), 2.1 (3 H, s). N- oC presently useful for preparation quantities methyl-N'-acetylpiperazine(39%): bp 129.0 129.8 (19.5torr) only the of small lH ((5 mmol) of products: yields decreasesignificanr"ly when (lit.25168'c (760torr)); NMR (CDCI3)6 3.50(4 H, m), ca. (7 (3 the reaction is scaled up. Our qualitative observations 2.3 H, superimposeds and m), 2.10 H, s). l/-Acetyl- py'rrolidine(51%): bp 111.0113.0'C (15torr); tH NMR (CDCI3) suggestthat the aggregationof sodium during the reaction, 6 3.21 (4 H, t), 2.0 (7 H, superimposeds and m). N,N-Diiso- and the consequent decreasein sodium surface, is an propylacetamide(85%): bp 97.5-99.0'C (24 torr) (lit.2a80 oC important contributor to this decreasein yield. It may be (13torr)); 1H NMR (CDCI3)6 3.6(2 H. broadm),2.05 (3 H, s), possibleto circumvent this problem by high-speedstirring 1.25(12 H, "t"). N,N-Diethylisobutyramidewas preparedfrom or by other mechanical or chemical means of maintaining isobutyric acid by conversionto its acid chloride (63%) with a high sodium surfacearea. Alternatively, electrochemical thionyl chloride and treatment with 2 equiv of diethylamine in reductions in DEA or NEP might prove valuable. Until diethyl ether:23bp 90.0-92.0"C (19 torr) (lit.26?5.0-76.0 "C (8 IH these possibilities have been tested experimentally, torr)); NMR (CDCI3)6 3.38(4 H, q),3.70(1 H, sep),1.1 (fZ however, the reaction should be considered only for H, superimposedd and t). small-scalepreparations. Preparation of Authentic Samples of Alcohol Products. Samples of various tertiary alcoholswere prepared in routine Although data regardingDEA other toxicity and amides fashion from ketonesand Grignard or lithium reagentsuand were are scarce,2othese solventshave the combination of high characterizedby standard spectroscopictechniques and com- solvent power and miscibility with both organic solvents parison of physical properties with literature values, when and water which would be expected to make them effective available, The boiling points and massspectral data of a series in facilitating passivetransport of both organic and in- of alcoholsthat were preparedfrom n-hexylmagnesiumchloride organic materials through the skin and cell walls. Solutions and the appropriate ketone are listed as follows. 7-Methyl-7- oC of toxic substancesin these solvents should be handled tridecanol: bp 156 158 (19torr); massspectrum mf e (relative with care. intensity)199 (7),130 (11),119 (100),111 (6),7I (7),69 (42),58 (5),57(6), 55 (11),45(5),43 (15),41 (8). 6-Methyl-6-dodecanol: bp 118-122'C (5 torr); massspectrum mf e (relativeintensity) Experimental Section 185(6),130 (7),129 (70),116 (8),115 (100),114 (5),111 (6),99 General Methods. Melting points were determined on a (7),97(20),85 (6),83 (6),71 (2t),70 (6),69 (57),59 (10),58 (19), Thomas-Hoovercapillary apparatusand are un- 57 (15),56 (14),55 (54),45 (32),44(9),43 (83), 42 (13),41(43). oC corrected. Boiling points are uncorrected. Infrared spectra (IR) 3-Ethyl-3-nonanol:bp 123.5 125.0 (30torr); massspectrum were recorded on a Perkin-Elmer Model 567 grating infrared mf e (relativeintensitv) 144 (8), 143 (80).88 (6),87 (100),85 (10), spectrometerand are reported in wavenumbers. Proton NMR 83 (27),73 (6),70 (5),69 (63),59 (18),57 (33),55 (22),45(28), spectra were determined on a Varian AssociatesModel T-60 43 (24),41Q4\,39 (6). 2-Methyl-2-octanol:bp 127.0-128.5"C spectrometer and are reported in parts per million downfield from (87 torr) (lit.2880'C (12.5torr)); massspectrum mf e (relative MeaSi. Mass spectrawere obtainedon a Varian Model MAT 44 intensity)129 (13),69 (17),59 (100),58 (5),55 (6),43 (14),41 (10). oC instrument at an ionizing voltageof 70 eV. Elemental analyses 1-n-Hexylcyclohexanol:bp 125.0-L27.0 (7 torr) (1ft.2e172'C were performed by Robertson Laboratory, Florham Park, N.J. (100torr)): massspectrum mf e (relativeintensity) 141 (8), 114 GLC analyseswere carried out on a Perkin-Elmer Model 990 or (4),113 (12), 100 (7),99 (100), 81 (34),72 (6),71(9),67 (8), 58 39208 chromatograph equipped with a flame ionization (8),57(16),55 (17),43 (i3),41 (13),29 (7). A sampleof 2,2,3- detector. Neopentyl and cyclohexylhalides were analyzedby using trimethyl-3-nonanolwas preparedfrom 1-lithiohexaneand pi- a 9-ft column of 20% SE-30 on 80-100 Chrom P; hydrocarbons nacolone: bp 122.0-123.0"C (24 torr); mass spectrum mf e were analyzed with a 30-ft column of l0To TCEP on 80 100 (relativeintensity) 130 (6), 129 (75),102 (6),101 (79),85 (13),83 Chrom P; secondaryalcohols and ketoneswere separatedon a (36),71(19),70 (7),69 (100),59 (27),58 (12),57 (33),55 (38),45 9-ft column of 5To Carbowax20M on 80-100Chrom W; tertiary (20),43 (57),41(43),39 (9),29 (30). 2,2-Dimethyl-3-nonanolwas alcoholswere detected following chromatography on a12-ft HiPak preparedfrom pivaldehydeand n-hexylmagnesiumchloride: bp oC column of UC-W98 on 80-100 WHP. Products were identified 145.0-146.0"C (92 torr) (lit.3090 (13 torr)); massspectrum by peak-height enhancementresulting from coinjection of an mle (relativeintensity) 115 (11),97 (45),96 (8),87 (16),71 (10), authentic sample and by massspectroscopy on a Hewlett-Packard 70 (7),69 (25),58 (6),57 (68),55 (100),54 (7),45 (13),44 (L5), 59924 GC/MS. Reagentgrade HMPA, DMA, NMP, DEA, NEP, 43 (52),42 (li\,41 (75),40 (10),39 (21). A sampleof 4,6-di- DEP, Me2SO,and DMF were obtained from commercialsources methyl-6-undecanolwas prepared from 2-heptanone and 2- oC and were purified by distillation from calcium hydride through methylpentyl-1-magnesiumbromide: bp 174.0-175.0 (98torr); a 26-cm column at reduced pressure. HMPA (bp 88.9-89.0oC massspectrum mf e (relativeintensity) 129 (54),116 (7), 115(100), (8 torr)), DEA (bp 105.0-107.0'C (61torr)), NEP (bp 78.0-78.5 111(9),97 (16),85 (18),83 (8),71 (29),70 (10),69 (33), 59 (27), "C (90torr)), and DEP (bp 81.3-82.0'C (10torr)) wereredistilled 58(11),57 (18),56 (11),55 (44),45 (16),43 (59),41 (30),39 (7), through the samecolumn from molten sodium.2r Reagentgrade 29 (22). The addition of ethylmagnesiumbromide to heptanone oC fert-butyl alcohol was distilled from sodium metal under nitrogen. afforded3-methyl-3-octanol: bp 113.0 114.5 (58 torr) (lit.3t 'C Reactantssuch as olefins and ketoneswere purified immediately 80-81 (15torr)); massspectrum m/e (relativeintensity) 129 before use by passagethrough a 2-in. column of grade I alumina. (13),115 (40),97 (9),i4 (11),73(100), ?l (8),70(8),69 (10),59 Dissolving-metalreductions and couplings were performed in (13),57(8),55 (33),45 (9),43 (17),41 (11). 2-Methyl-2-butanol 15-mL polymerization tubes (Lab Glass)that were sealedwith was obtainedcommercially. 0.25-in.butyl rubber septa and crown caps. All reactionswere Authentic samplesof cyclic tertiarv alcoholswere prepared from carried out in flame-driedglassware under an inert atmosphere the appropriatecycloalkanone and methyllithium. A sampleof of prepurified nitrogen or argon by using routine techniquesfor 2-methylcyclooctanonewas synthesized according to a literature handling oxygen- and moisture-sensitivematerials.22 procedure;32all other ketones were obtained commercially. General Preparation of Ethylamides. Additional amides were preparedby routine methods.B N-Acetylmorpholine (79%): lH (241 bp 139.0-139.8"C (26torr) (lit.24117-118 (13 torr)); NMR Chem. Abstr. 1956,50,i112. (25)Nakajima. K. Rull Chem.Soc. Jpn.,1961, 3.1, 651-4. (26)Miller, L. L.; Johnson,J. R. J. Org.Chem.1936, /, 135-40. (27)Reference 2l), pp 879 81. (20) Christenson,H. E., Ed., "Toxic SubstancesList, 1973Ed."; NIOSH: (28) Williams,F. E.;Whitmore, F. C. J. Am. Chem.Soc.1933, 55, 406-11. Rockville,Md., 1973;p 3. (29)Williams, H. B., EdwardsW. R., Jr.J. Am. Chem.Soc. 1947,69, (21) Burfield,D. R.; Lee, K.-H.; Smithers,R. H. J. Org.Chem.1977, 336,8. 42,3060 5, (30) Zavada.,J.;Pdnkova, I\{.; Sicher, J. CoLlect.Czech. Chem. Commun. (22) Shriver, D. F. "The Manipulation of Air-SensitiveCompounds"; 1972.,37,2414 35. McGraw-Hill: New York, N.Y., 1969;pp 145 205. (ill) Jamison.M. M.; Lesslie,M. S.;Turner,E. E. J. Inst.Pet.1949, (23) Hilgetag,G.; Martini, A., Eds.,"Preparative Organic Chemistrv"; ,r5.590 620. Wiley: New York, N.Y., 19?2;pp 484 8. (ll2) Girard. C.; Conia,,J. M. TetrahedronLett. 1973,276770. Reductive Coupling of Ketones with Olefins J. Org. Chem., Vol. 44, No. 14, 1979 2375

Spectraland physicalproperties of this seriesof compoundsare canted from the unreactedsodium and cautiously treated with as follows. l-Methylcyclopentanol bp 74.0-75.5oC (64 torr) (lit.m water (10 mL). The mixture was extracted with three 15-mL 134oC (760torr)); massspectrum mf e (relativeintensity) 85 (14), volumes of pentane (98%), and the combined extracts were 84 (6),72(8),71(100),70 (7),67 (14),59 (6),58 (71), 57 (27),56 washedwith three 15-mL volumes of water. The solution was (8),55 (27),53(5), 45 (8),44 (5),43 (96),42 12\,41(29),40 (7), dried over magnesium sulfate. GLC analysis revealed 6- 39 (19). Racemic1,2-dimethylcyclopentanol: bp 83.0 86.0"C methyl-6-dodecanol (65 % ), 2-heptanol(37 % ), 2-heptanone (