Alkylation of Alkenes - Organische Chemie - Metzger

12 Pages·2004·0.19 MB·English

PublishedonWeb07/28/2004
Alkylation of Alkenes: Ethylaluminum
Sesquichloride-Mediated Hydro-Alkyl Additions with Alkyl
Chloroformates and Di-tert-butylpyrocarbonate
Ursula Biermann and Ju¨rgen O. Metzger*
ContributionfromtheDepartmentofPureandAppliedChemistry,UniVersityofOldenburg,
D-26111Oldenburg,Germany
ReceivedFebruary26,2004; E-mail:[email protected]
Abstract:Ageneralmethodforthehydro-alkyladditiontothenonactivatedCdCdoublebondofalkenes
using alkyl chloroformates (primary, secondary), 12, and di-tert-butylpyrocarbonate, 52, mediated by
ethylaluminumsesquichloride(Et Al Cl )hasbeendeveloped.Reactionof 12and52,respectively,with
3 2 3
Et Al Cl givesanalkylcationwhichisaddedtothealkene;hydridetransfertotheadductcarbeniumion
3 2 3
or,ifapplicable,1,2-HshiftfollowedbyhydridetransferfromEt Al Cl totherearrangedadductcarbenium
3 2 3
iongivesthesaturatedadditionproduct.Thereactionhasbeenappliedto1-alkenes,2-methyl-1-alkenes,
internal double bonds, and to three cyclic alkenes. Special interest has been focused on alkylations of
unsaturated fatty compounds, such as oleic acid (2), which are important renewable feedstocks.
2-Methylalkanes,3-methylalkanes,2,4-dimethylalkanes,2,3-dimethylalkanes,2,2,4-trimethylalkanes,cy-
clohexylalkanes, and carboxylic acids and esters with the respective branched alkyl chain have been
synthesizedwithgoodtomoderateyields.
Introduction particular,consideredfactorswhichwouldfavortheformation
of mono-alkylation products. It was stated that 1:1 addition
The alkylation of alkenes is of considerable importance.1
products are formed if the alkyl halide reacts faster with the
However, there are no methods for the direct alkylation of
alkene than with the alkylation product; otherwise, higher
nonactivated CdC double bonds with alkyl residues, such as
addition products will be obtained.7 The relative dissociation
the isopropyl group. Thermal radical additions of alkanes are
ratesofthealkylhalideandthealkylationproductinducedby
applicabletoterminaldoublebondsonly,nottointernaldouble
theLewisacidshouldreflecttheirrelativeratesofadditionto
bonds.2,3 Cationic additions are restricted to tertiary alkanes:
a common alkene.7a Thus, mono alkylation products with
for example, the formation of isooctane by the reaction of
isopropylhalideswereneitherobtainedinreactionswithpropene
isobutene and isobutane in the presence of concentrated acids
and isobutene7b nor in the corresponding reactions with buta-
andsuperacids.4Friedel-Craftsalkylationsofalkenesarerarely
dieneandisoprene.11Exclusively,oligomersandpolymerswere
usedinpreparativeorganicsynthesistoformnewCsCbonds
formed. In contrast, the AlCl -induced condensation of tert-
3
because they tend to give mixtures of products, including
butyl chloride with propene afforded a mixture of isomeric
oligomersandpolymersofalkenesandmostlynotthedesired
heptyl chlorides in 70% yield.12 The formation of isomers
mono alkylation products.5 Alkylations of alkenes have been
depends on the applied Lewis acid.13 Mayr and Striepe found
thoroughly investigated by Olah6 and Mayr,7-10 who, in
thatthereactionoftert-butylchlorideandpropeneinducedby
ZnCl (cid:226)Et O gave exclusively the mono-alkylation product
2 2
(1) Industrial and Laboratory Alkylations; Albright, L. F., Goldsby, A. R.,
2-chloro-4,4-dimethylpentane.7b
Eds.;ACSSymposiumSeries1977;AmericanChemicalSociety: Wash-
ington,DC,1978. It is known that alkyl chloroformates are fragmented in the
(2) Metzger,J.O.J.Prakt.Chem.1990,332,767-781.
(3) Metzger,J.O.;Bangert,F.FatSci.Technol.1995,97,7-9. presenceofAlCl3,withformationofCO2andthecorresponding
(4) (a) Pines, H. In The Chemistry of Catalytic Hydrocarbon ConVersions; carbeniumions.14,15Also,silver(I)-induceddechlorodecarboxyl-
AcademicPress: NewYork,1981;pp50-58.(b)Nenitzescu,C.D.In
CarboniumIons;Olah,G.A.,vonR.Schleyer,P.,Eds.;Wiley: NewYork, ations were used to generate reactive carbocations from alkyl
1970; Vol. II, pp 463-520 (at p 504). (c) Olah, G. A.; Farooq O.;
Krishnamurthy,V.V.;Prakash,G.K.S.;Laali,K.J.Am.Chem.Soc.1985,
107,7541-7545.(d)Olah,G.A.;Batamack,P.;Deffieux,D.;Torok,B.; (9) (a)Mayr,H.;Schneider,R.;Schade,C.;Bartl,J.;Bederke,R.J.Am.Chem.
Wang,Q.;Molnar,A.;Prakash,G.K.S.Appl.Catal.,A1996,146,107- Soc. 1990, 112, 4446-4454. (b) Mayr, H.; Schneider, R.; Irrgang, B.;
117.(e)Olah,G.A.;Marinez,E.;Torok,B.;Prakash,G.K.S.Catal.Lett. Schade,C.J.Am.Chem.Soc.1990,112,4454-4459.
1999,61,105-110. (10) (a)Mayr,H.;Patz,M.Angew.Chem.1994,106,990-1010;Angew.Chem.,
(5) Kennedy, P.; Mare´chal, E. In Carbocationic Polymerization; Wiley- Int.Ed.Engl.1994,33,938-957;(b)Mayr,H.;Bug,T.;Gotta,M.F.;
Interscience: NewYork,1982;p82. Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.;
(6) Olah,G.A.;Kuhn,S.J.;Barnes,D.G.J.Org.Chem.1964,29,2685- Remennikov,G.;Schimmel,H.J.Am.Chem.Soc.2001,123,9500-9512.
2687. (11) Petrov,A.A.;Leets,K.V.Zh.Obshch.Khim.1956,26,1113,Chem.Abstr.
(7) (a)Mayr,H.Angew.Chem.1981,93,202-204;Angew.Chem.,Int.Ed. 1956,50,11936d.
Engl.1981,20,184-186.(b)Mayr,H.;Striepe,W.J.Org.Chem.1983, (12) Miller,V.A.J.Am.Chem.Soc.1947,69,1764-1768.
48,1159-1165. (13) Schmerling,L.J.Am.Chem.Soc.1953,75,6217-6222.
(8) Mayr,H.Angew.Chem.1990,102,1415-1428;Angew.Chem.,Int.Ed. (14) Kevill,D.N.InTheChemistryofAcylHalides,ChloroformateEstersand
Engl.1990,29,1371-1384. RelatedCompounds;Patai,S.,Ed.;Wiley: London1972,pp425-433.
10.1021/ja048904yCCC:$27.50 ©2004AmericanChemicalSociety J.AM.CHEM.SOC.2004,126,10319-10330 9 10319
ARTICLES BiermannandMetzger
Scheme1. Friedel-CraftsAlkylationofArenesbyAlCl3-Induced
FormationofCarbeniumIonsfromChloroformates14a
a(Ar)Aryl,R)Alkyl)
chloroformates.16 Previously Friedel and Crafts,17 as well as
Rennie,18 showed that benzene is ethylated with ethyl chloro-
formate in the presence of AlCl (Scheme 1).
3
Our special interest lies in the alkylation of long-chain
unsaturatedfattycompounds,suchasoleicacid(2),sincethey
arerenewablerawmaterialsofincreasingsignificance19-21and
alkyl-branched fatty compounds have interesting properties
which make them attractive for use in cosmetic and lubricant
applications.22,23 Most of these characteristics, such as good
spreadability,lowviscosity,andgoodoxidativeandhydrolytic
stability, are shown by the commercially available product
“isostearic acid” that is used in cosmetics and lubricants.
However, this commercial isostearic acid that is formed as a
byproductinthemontmorillonite-induceddimerizationprocess
of oleic acid is not at all a pure compoundsit consists of a
mixtureofanimmensenumberofcomponents.24Thesynthesis
of well-defined and completely characterized alkyl-branched
fatty compounds by an addition reaction to, e.g., oleic acid,
would be important.
We now report the results of our study, aimed to develop a
general synthetic method for the hydro-alkylation of nonacti-
vatedCdCdoublebondsofalkeneswithalkylchloroformates
mediatedbyethylaluminumsesquichloride(Et Al Cl ).Dichlo- Figure1. Alkenes1-11usedinalkylationreactions.
3 2 3
romethane has been used as solvent without any nucleophilic
properties.Weperformedasystematicinvestigationofthescope
of the reaction with respect to alkenes (Figure 1) and to alkyl
chloroformates(Figure2)andcouldestablishreactionconditions
that allow the synthesis of the desired alkylation products in
good to moderate yields.25
Results
First, we studied the hydro-alkyl addition to the 1,2-disub-
stituted CdC double bond of alkenes, such as trans-4-octene
(15) (a) Olah, G. A.; Olah, J. A. In Carbonium Ions; Olah, G. A., von R.
Schleyer,P.,Eds.;Wiley: NewYork,1970;Vol.II,pp715-782(atp
765).(b)Kirmse,B.TopCurr.Chem.1979,80,125-311(atp172).
(16) Beak,P.Acc.Chem.Res.1976,9,230-236.
(17) Friedel,C.;Crafts,J.M.C.R.SeancesAcad.Sci.1877,84,1450-1454.
(18) Rennie,E.H.J.J.Chem.Soc.1882,41,33.
(19) (a)Biermann,U.;Friedt,W.;Lang,S.;Lu¨hs,W.;Machmu¨ller,G.;Metzger,
J.O.;Ru¨schgen.Klaas,M.;Scha¨fer,H.J.;Schneider,M.P.Angew.Chem.
2000,112,2292-2310;Angew.Chem.,Int.Ed.2000,39,2206-2224.(b)
Biermann,U.;Metzger,J.O.Top.Catal.2004,27,119-130.(c)Eissen,
M.;Metzger,J.O.;Schmidt,E.;Schneidewind,U.Angew.Chem.2002, Figure2. Alkylationagents: alkylchloroformates12a-l.
114,402-425;Angew.Chem.,Int.Ed.2002,41,414-436.
(20) SynthesesofNoVelFattyAcidDeriVatiVes;Knothe,G.,Derksen,J.T.P.,
(1),oleicacid(2),methyloleate(3),andmethylricinoleate(4),
Eds.;AmericanOilChemistsSociety: Champaign,IL,1999.
(21) Biermann,U.;Fu¨rmeier,S.;Metzger,J.O.InOleochemicalManufacture andofcyclicalkenes,suchascyclohexene(5)andcyclopentene
and Applications; Gunstone, F. D., Hamilton, R. J., Eds.; Sheffield
AcademicPressandCRCPress: BocaRaton,FL,2001,266-299. (11), using chloroformates of secondary alcohols, such as
(22) Kinsman,D.V.InFattyAcidsinIndustry;Johnson,R.W.,Fritz,E.,Eds.; isopropyl(12a),cyclohexyl(12b),and2-pentylchloroformate
MarcelDekker: NewYork,1989;pp233-276.
(23) Johnson, R. W., Jr.; Cantrell, R. R. In Kirk Othmer Encyclopedia of (12c),asalkylatingagents(Table1).Allproductswereunam-
Chemical Technology, 4th ed.; New York: Wiley, 1993; Vol. 5, 189- biguouslyidentifiedandcharacterizedby1HNMR,13CNMR,
192.
(24) TechnicalDataSheet,Emersol874IsostearicAcid,HenkelCoorporation: GC/MS,andifapplicable,bycomparisonwithliteraturedata.
GulphMills,PA,1999. Dropwiseadditionofethylaluminumsesquichloride(Et Al -
(25) Forapreliminaryaccountofourresults,see: Biermann,U.;Metzger,J. 3 2
O.Angew.Chem.,Int.Ed.1999,38,3675-3677. Cl3)toamixtureofalkene1andisopropylchloroformate(12a)
10320 J.AM.CHEM.SOC.9VOL.126,NO.33,2004
AlkylationofAlkeneswithEthylaluminumSesquichloride ARTICLES
Table1. EthylaluminumSesquichloride(Et3Al2Cl3)-InducedAlkylationsofAlkenes1-11withSecondaryAlkylChloroformates: Isopropyl
(12a),Cyclohexyl(12b),and2-PentylChloroformate(12c)
aIsolatedyieldswereobtainedbyKugelrohrdistillationsexceptforproducts14/15,20/21,27,29,and30/31whichwereobtainedbycolumnchromatography
(seeExperimentalSection).bTheregioisomericproducts18and19wereobtainedasmixturesofdiasteromers,respectively,inratiosof7:1(18)and5:3
(19).cThereactionwascarriedoutwithequimolaramountsofEt3Al2Cl3andtriethylsilane.
J.AM.CHEM.SOC.9VOL.126,NO.33,2004 10321
ARTICLES BiermannandMetzger
Scheme2. MechanismoftheHydro-AlkylationofInternalAlkenes The hydro-alkyl addition to cyclic alkenes, such as cyclo-
withIsopropylChloroformate(12a)andEthylaluminum
hexene(5)andcyclopentene(11),withisopropylchloroformate
Sesquichloride
(12a)underthestandardreactionconditionsdescribedforalkene
1occurredwithonlymoderateyields,e.g.,40%,ofisopropyl-
cyclohexane(22).Productmixtures,whichconsistedmainlyof
oligomers,wereformed.However,theformationofthemono-
alkylation products could be favored by addition of a more
effective hydride donor, such as triethylsilane.10 Thus, the
isopropylationof5,whichwascarriedoutbydropwiseaddition
of an equimolar mixture of triethylsilane and Et AlCl to the
3 3
mixtureof5and12a,affordedisopropylcyclohexane(22)ina
remarkable yield of 82% (Table 1, entry 6).25 The oligomer-
izationwasextensivelysuppressedusingthesemodifiedstandard
reactionconditions.Isopropylcyclopentane(23)wassynthezised
indichloromethaneinaratioof1:1:1gave,after1hofreaction in 69% yield using comparable reaction conditions (Table 1,
time at -15 (cid:176) C and stirring for an additional 1 h at room entry7).Remarkably,cis-andtrans-1,2-dimethylcyclohexane
temperature,thehydro-alkyl-additionproduct4-isopropyloctane were detected as minor products (together, 3.5%) by GC/MS.
(13) in 67% yield (Table 1, entry 1). These are the standard The reaction was also applied to the trialkyl-substituted CdC
reactionconditionsthatareusedinthefollowingexperiments. doublebondof1-methylcyclohexene(6).Thealkylationof6
Itisimportanttouse1equivofEt Al Cl ;0.5equivisnecessary with12awasalreadycompleteafterareactiontimeof1hand
3 2 3
forthechloroabstractionfromthechloroformate,and0.5equiv gave o-menthane, 24, in a yield of 49% as a diastereomeric
is consumed in the hydride transfer to the adduct carbenium mixtureinaratioof[trans-24]:[cis-24])1.5:1(Table1,entry
8). The isopropylation of 2-methyl-1-undecene (8), using
ion(seeScheme2).Rearrangedadditionproductsandisomeric
standardreactionconditions,yieldedonly10%of2,4-dimeth-
ethyl-isopropyloctanes were formed in small amounts, about
yltridecane (26). An additional product formed, in 45% yield,
10%oftheoverallyield.Mostreactionsdescribedinthispaper
showed comparable minor products (<10%) that will be was 10,10,13-trimethyleicosane, the hydrodimer of 8, as was
shownbyGC/MS.Additionofequimolaramountsoftriethyl-
outlined,furthermore,onlyinspecialexamples.Chloroisopro-
silane afforded a 47% yield of 26 but did not suppress the
pyloctanes and isopropyloctenes were not detected, or were
formation of the dimer completely (Table 1, entry 10). Most
detected only in trace amounts, by GC/MS. The range of
interestingwasthehydro-isopropyladditionto1-alkenes,giving
temperaturethatcanbeusedtoperformthereactionsuccessfully
selective access to 2-methylalkanes. The reaction of 1-octene
is very small, thus preventing the investigation of the temper-
(7), 10-undecenoic acid (9), and methyl 10-undecenoate (10)
ature dependence.
was studied. Under standard reaction conditions, the desired
Alkylationsofunsaturatedfattycompounds2and3,contain-
additionproductswereobtainedinlowyieldsonly(e.g.,reacting
ingtwodifferentalkylsubstituentsatthecis-configureddouble
chloroformate12awith10-undecenoicacid(9)producedhydro-
bond, afforded the regioisomeric mixtures of 9- and 10- alkyl-additionproduct27in10%yield,asdeterminedbyGC,
isopropyloctadecanoic acid (14 and 15) and the respective because of dimerization and oligomerization of alkene 9). By
methylesters(16and17)in73%and71%yield,respectively applying modified standard reaction conditions with addition
(Table 1, entries 2 and 3). The regioisomers that could not be of equimolar amounts of triethylsilane (alkene:12a:Et Al Cl :
3 2 3
separated by chromatographic and other usual separation Et SiH)1:1:1:1),oligomerizationofthealkeneswasconsider-
3
methods were obtained in a ratio of approximately 1:1. A ably suppressed so that the mono-alkylation products 25, 27,
respective mixture of the regioisomers 9- and 10-cyclohexyl- and 28 were isolated in yields of 55%, 60%, and 72%,
octadecanoicacid(20and21)wasformedonreactionofalkene respectively (Table 1, entries 9, 11, and 12).
2 with cyclohexyl chloroformate (12b) (Table 1, entry 5). It The hydro-cyclohexyl addition to 1-alkenes opens an easy
seemstoberemarkablethattheyieldisnotdiminishedreacting way to 1-cyclohexylalkanes. Reaction of 10-undecenoic acid
substrates with carboxy and ester functionalities. In these (9) with cyclohexyl chloroformate (12b) in the presence of
reactions,itisimportanttoapply1.5equivofEt3Al2Cl3because equimolaramountsofEt3Al2Cl3andtriethylsilaneafforded11-
0.5 equiv is used by the carboxy group and the ester group, cyclohexylundecanoic acid (29) in an isolated yield of 58%
respectively.Also,anadditionalhydroxygroupinthe(cid:226)-position (Table 1, entry 13).
relativetotheCdCdoublebondistolerated.Theisopropylation 2-Pentyl chloroformate (12c) as a further secondary alkyl
of methyl ricinoleate (4) gave the alkylation products in 60% chloroformate was studied additionally because of a possible
yieldasamixtureofthetworegioisomers18and19inaratio rearrangementoftheintermediate2-pentylcation.Asexpected,
ofapproximately1:1.Bothwereformedasapairofdiastereo- incontrasttotherespectivereactionswithchloroformates12a
mers; 18 in a ratio of 7:1 and 19 in a ratio of 5:3. The and 12b, alkylation products obtained with 12c were formed
diastereomersweredistinguishablebyGCanalysisandbythe as mixtures of isomers. The alkylation of 10-undecenoic acid
13CNMRspectrum,buttheycouldnotbeassignedunambigu- (9) yielded 72% of a mixture of 12-methylpentadecanoic acid
oulytotherespectivecompounds.Inthisexample,2equivof (30)and12-ethyltetradecanoicacid(31)inaratioof1.2:1(Table
EtAlCl hadtobeappliedbecausethereactionoftheadditional 1,entry14).3-Pentylchloroformate(12l)yieldedthesameratio
3 2 3
hydroxyl group with Et Al Cl consumes 0.5 equiv (Table 1, of the respective isomers in the corresponding reaction with
3 2 3
entry 4). cyclohexene (5) (Table 2, entry 6).
10322 J.AM.CHEM.SOC.9VOL.126,NO.33,2004
AlkylationofAlkeneswithEthylaluminumSesquichloride ARTICLES
Table2. EthylaluminumSesquichloride(Et3Al2Cl3)-InducedAlkylationsofAlkenes2,5,and9withLinearPrimaryAlkylChloroformates:
1-Propyl(12d),1-Butyl(12e),1-Pentyl(12f),and1-HexylChloroformate(12g)
aIsolated yields were obtained by column chromatographysexcept for product 35, which was obtained by Kugelrohr distillation (see Experimental
Section).bThereactionwascarriedoutwithequimolaramountsofEt3Al2Cl3andtriethylsilane.cUsing3-pentylchloroformate(12l),theratioof[36]:[37]
)1.2:1wasobtained.
Having investigated the very general addition reactions of equimolaramountsoftriethylsilaneshowedtheadditionofthe
secondaryalkylchloroformates,wedrawourattentiontolinear 2-butyl cation, yielding 72% of 12-methyltetradecanoic acid
primaryalkylchloroformates.Reactionsofethylchloroformate (34).Cyclohexene(5)yieldedonly30%ofsec-butylcyclohexane
(12k)with1-alkenesunderstandardreactionconditions,aswell (35). In addition, cyclohexylcyclohexane (36%, GC) was
aswithaddedtriethylsilane,gaveoligomerizationofthealkene, formed,theformationofwhichcouldnotbesuppressedbythe
e.g., the reaction of 9 and chloroformate 12k resulted in the addition of Et SiH.
3
formationofamixtureofC22dicarboxylicacidsin70%yield, Higher linear alkyl chloroformates are expected to give
aswasshownbyGC/MS.However,reacting1-propylchloro- isomers by addition of the possible secondary alkyl groups
formate(12d)understandardreactionconditionswitholeicacid which can be formed by Wagner-Meerwein rearrangements.
(2)gaveamixtureof9-and10-isopropyloctadecanoicacid(14, Thus, alkylation of alkene 5 with chloroformate 12f in the
15)inayieldof71%(Table2,entry1).Thus,thesameproduct presence of triethylsilane yielded mixtures of 2- and 3-cyclo-
mixture and almost the same yield were obtained as with hexylpentaneinaratioof[36]:[37])1.3:1.Aproductratioof
isopropylchloroformate(12a)(Table1,entry2).Analogously, 1.2:1 was obtained using 3-pentyl chloroformate (12l) (Table
reactionofchloroformate12dand10-undecenoicacid(9)with 2,entry6).Amixtureof12-methylhexadecanoicacid(40)and
addedtriethylsilanegave12-methyltridecanoicacid(27)in56% of12-ethylpentadecanoicacid(41)inaratioof[40]:[41])1.1:1
yield (Table 2, entry 2). wasobtainedfromthealkylationofalkene9withchloroformate
Using1-butylchloroformate(12e)inthereaction,theaddition 12g in the presence of triethylsilane (Table 2, entry 8).
of the sec-butyl group could be expected. Indeed, reaction of Approximatelythesameratioofproducts38and39wasformed
oleic acid (2) under standard reaction conditions with chloro- with alkene 5 (Table 2, entry 7).
formate 12e afforded the regioisomeric mixture of 9- and 10- Itseemsworthmentioningthat,inallexamplesofreactions
sec-butyloctadecanoicacid(32,33)in74%yield.Analogously, with primary alkyl chloroformates investigated, no hydro-1-
reactionofalkene9withchloroformate12einthepresenceof alkyl-additionproductscouldbedetected.Primaryalkylchlo-
J.AM.CHEM.SOC.9VOL.126,NO.33,2004 10323
ARTICLES BiermannandMetzger
Table3. EthylaluminumSesquichloride-InducedAlkylationsofAlkenes2,5,9,and11withBranchedPrimaryAlkylChloroformates:
Isobutyl(12h)andNeopentylChloroformate(12I)
aIsolatedyieldswereobtainedbycolumnchromatography(32/33/42/43,34/44,and46/47)orbyKugelrohrdistillation(35/45/54,48/49,and50/51)(see
ExperimentalSection).bThereactionwascarriedoutwithequimolaramountsofEt3Al2Cl3andtriethylsilane.c1:1Mixtureofdiastereomers.
Table4. EthylaluminumSesquichloride-InducedAlkylationsof
roformates that are branched at C-2 lead to the formation of Alkenes2,5,8,9,and11withDi-tert-butylpyrocarbonate(52)
interesting,rearrangedadditionproducts.Wetreated,therefore,
oleicacid(2)withisobutylchloroformate(12h)inthepresence
of Et Al Cl and obtained a mixture of hydro-alkyl addition
3 2 3
products32,33and42,43in74%overallyield(Table3,entry
1).Regioisomers32and33werealsoformedbyreactionof2
with1-butylchloroformate(12e)(Table2,entry3).Regioiso-
mers42and43aretheproductsofhydro-tert-butyladditionto
the double bond and were also formed by reacting alkene 2
withdi-tert-butylpyrocarbonate(52)(Table4,entry1).Theratio
of([32]+[33]):([42]+[43])wasapproximately2:1.Reactionof
thesamechloroformate,12h,with1-alkene9showedadifferent
outcome of products. Two isomeric addition products 34 and
44, in a ratio of 1:2.2, were obtained. Whereas 34 was also
obtained by addition of 1-butyl chloroformate (12e), no tert-
butyl addition product was observed. Instead 11,12-dimethyl-
tridecanoicacid(44)wasformed(Table3,entry2),whichwas
also obtained by reaction of 9 with di-tert-butylpyrocarbonate
(52)(Table4,entry2).Therespectivereactionofcyclohexene
(5) gave 2-butylcyclohexane (35), 1-isopropyl-1-methylcyclo-
hexane(45),andtert-butylcyclohexane(54)inaratioof12.5: aIsolatedyieldswereobtainedbycolumnchromatography(42/43and
44) or by Kugelrohr distillation (53, 45/54, and 55) (see Experimental
2.5:1. Product 35 was also formed in the reaction with
Section).bThereactionwascarriedoutwithequimolaramountsofEt3Al2Cl3
chloroformate 12e (Table 2, entry 5), and products 45 and 54 andtriethylsilane.
10324 J.AM.CHEM.SOC.9VOL.126,NO.33,2004
AlkylationofAlkeneswithEthylaluminumSesquichloride ARTICLES
wereobtainedbyreactionwithdi-tert-butylpyrocarbonate(52). 2, entry 4). 2,4-Dimethylalkanes may be obtained by reaction
(Table 3, entry 3; see also Table 4, entry 4). of 2-methyl-1-alkenes with isopropyl chloroformate (Table 1,
Itisremarkablethatthealkylationsof9and5with12h(Table entry10),and2,3-dimethylalkanesmaybeobtainedbyreaction
3, entries 2 and 3) showed only very small amounts of of1-alkeneswithdi-tert-butylpyrocarbonate(52)(Table4,entry
oligomerizationproducts(>8%),althoughtheywerecarriedout 2). Reacting 2-methyl-1-alkenes with 52 can provide 2,2,4-
under standard reaction conditions without addition of trieth- trimethylalkanes (Table 4, entry 3). Cyclohexylalkanes can
ylsilane. In all examples described here, no trace of a hydro- generallybesynthesizedbyreactingcyclohexylchloroformate
isobutyl-addition product could be observed. (12b)withalkenes(Table1,entries6and13).11-Cyclohexyl-
Next,neopentylchloroformate(12i)wasreactedwithalkene undecanoic acid (29) is known to be the main lipid of
9. 11,12-Dimethyltetradecanoic acid (46) and 11-ethyl-12- thermophilicarchaebacteria.27Thesynthesisofthemethylester
methyltridecanoicacid(47)wereformedinaratioof2.2:1and of 29 has been performed by thermal radical addition of
isolated in an overall yield of 70% (Table 3, entry 4). 46 was cyclohexanetothemethylesterof9(yield)30%),3amethod
formed as a diastereomeric mixture in a ratio of about 1:1, as which is restricted to 1-alkenes for the synthesis of 1-cyclo-
was shown by 13C NMR. The respective reaction with cyclo- hexylalkanes.2
hexene (5) afforded 1-ethyl-1-isopropylcyclohexane (48) and The main phenomena emerging from the results described
1-(2-butyl)-1-methylcyclohexane (49) in a ratio of 1.3:1 and intheprecedingsection,whichshouldbeposedfordiscussion,
an overall yield of 84% (Table 3, entry 5). Most interesting certainly are the differences in the substitution patterns of the
results were obtained reacting cyclopentene (11) with chloro- addition products which may be influenced by the respective
formate12i.Amixtureof1-ethyl-1,2-dimethylcyclohexane(50) alkyl group of the chloroformate 12, as well as by the alkene
and1-ethyl-2,2-dimethylcyclohexane(51)inaratioof2.8:1and being reacted. Furthermore, an important phenomenon to be
anoverallyieldof65%wereobtained.Thetwodiastereomers explained is the fact that the hydro-alkyl addition could be
of50wereformedunselectivelyinaratioofabout1:1,aswas performed in many cases, e.g., with internal alkenes, under
shown by 13C NMR. standard reaction conditions with the reagent ethylaluminum
Finally,wewereinterestedinthepossibilityoftheaddition sesquichloride only, whereas in other examples, e.g., with
ofthetert-butylgrouptononactivateddoublebondsofalkenes. 1-alkenes,thestandardreactionconditionshadtobemodified
Becauseofitsthermalinstability,tert-butylchloroformatecould bytheadditionoftriethylsilaneasanadditionalhydridedonor
notbeused,correspondingto12a-l,tostudythesereactions, to suppress the formation of oligomers. In contrast, when
so di-tert-butylpyrocarbonate (52) was applied to perform the reacting alkenes 6 and 8, the formation of dimers could only
reaction with alkenes 2, 5, and 9 (Table 4). To our complete partiallybesuppressedbytriethylsilane.Thereactionmechanism
satisfaction, pyrocarbonate 52 behaved as the chloroformates, should be able to explain these phenomena.
12.Theproductsobtainedwerealreadydescribedforreactions The basic reaction mechanism can be rationalized easily if
with isobutyl chloroformate 12h. Reaction of alkene 8 with alkylations were carried out with simple secondary alkyl
pyrocarbonate 52 gave 2,2,4-trimethyltridecane (53), which chloroformates,suchasisopropylchloroformate(12a)(Scheme
could be isolated in 43% yield only (Table 4, entry 3). The 2).InthepresenceofEt Al Cl ,chloroformate12adecomposes
3 2 3
dimerizationof8,whichresultedintheformationofabout18% by formation of CO and the isopropyl cation, which adds to
2
of 10,10,12-trimethylicosane (GC), could not also be fully theCdCdoublebondofaninternalalkenetogiveasecondary
suppressed in the presence of Et SiH. adduct carbenium ion I. One could have thought that hydride
3
Finally, cyclopentene (11) was reacted with 52 (11:52:Et - transfertoadductcarbeniumionIgivesthehydro-alkyl-addition
3
Al Cl ) 2:1:2). To our surprise, we isolated 1,1,2-trimethyl- product. However, a 1,2-H shift affording the more stable
2 3
cyclohexane (55) in 60% yield (Table 4, entry 5). tertiary carbenium ion II, possibly being in equilibrium with
ion III, seems to be faster, as can be seen in the addition
Discussion
reactionsoftert-butylcation(seee.g.,Scheme7).Subsequent
Thenewlydevelopedprotocolofhydro-alkylationofalkenes transferofahydrideionfromanethylaluminumspeciestothe
ismostimportantfromapreparativepointofview.Nonactivated tertiarycarbeniumionsIIand/orIIIandeliminationofethene
CdCdoublebondsofalkeneshavebeenhydro-alkylatedusing lead to the hydro-alkyl addition product. It is known that
averygreatvarietyofprimaryandsecondaryalkylchlorofor- ethylaluminumcompoundscantransferhydrideionsaswellas
mates, 12, and di-tert-butylpyrocarbonate (52). Various func- ethylgroups;28notably,inthiscase,thehydrideionistransferred
tionalgroupsinthesubstratearetolerated.Thus,oleicacid(2), significantly more rapidly than the ethyl group, as is demon-
a renewable feedstock, was hydro-isopropylated to give a 1:1 strated by the small amount of ethylated products in most
mixture of 9- and 10-isopropylstearic acid (14, 15) (Table 1, reactions. In addition, as shown in Scheme 3, chloride might
entry 2) betransferredaswelltothecarbeniumiontogivealkyl-chloro-
The protocol allows for the highly efficient synthesis of addition products,7b and a proton could be eliminated to give
2-methylalkanes (isoalkanes) by reaction of 1-alkenes with alkyl-dehydrogenationproducts.29Thepossibleproductsofthese
isopropyl and 1-propyl chloroformate (Table 1, entries 9, 11, two competitive reactions could not be observed and were
12; Table 2, entry 2). (cid:246)-Unsaturated fatty acids give, most formedsifatallsinverysmallamounts.Finally,therearranged
easily,((cid:246)-1)-methyl-branchedisofattyacids,animportantclass adduct carbenium ion could be trapped by the alkene to give
ofnaturalcompounds.Isofattyacidshavebeensynthesizedin
(27) (a)Handa,S.;Floss.H.G.Chem.Commun.1997,153-154.(b)Floss,H.
a multistep procedure by Fordyce and Johanson.26 3-Methyla- G.Nat.Prod.Rep.1997,14,433-452.
lkanesareformedbyreactionwith1-butylchloroformate(Table (28) Snider, B. B.; Rodini, D. J.; Karras, M.; Kirk, T. C.; Deutsch, E. A.;
Cordova,R.;Price,R.T.Tetrahedron1981,37,3927-3934.
(29) Snider,B.B.;Rodini,D.J.;Kirk,T.C.;Cordova,R.J.Am.Soc.1982,
(26) Fordyce,C.R.;Johnson,J.R.J.Am.Chem.Soc.1933,55,3368-3372. 104,555-563.
J.AM.CHEM.SOC.9VOL.126,NO.33,2004 10325
ARTICLES BiermannandMetzger
Scheme3. PossibleCompetitiveReactionsoftheHydro-Alkyl Scheme4. MechanismoftheReactionof2-Methyl-1-undecene
AdditionShownfortheRearrangedAdductCarbeniumIonII.Ana- (8)withtheIsopropylCationGeneratedfromIsopropyl
logousReactionsArePossiblewithCarbeniumIonIII(Scheme2) Chlorformate(12a)inthePresenceofEt3Al2Cl3(seeScheme2)
GivingAlkylationProduct26andHydrodimer
10,10,13-Trimethyleicosane
Scheme5. ReactionofPentylChloroformates12fand12linthe
PresenceofEt3Al2Cl3withCyclohexene(5)andof12cwith
10-UndecenoicAcid(9)GivingtheHydro-AlkylationProducts36,
37and30,31,Respectively
oligomers. This latter competitive reaction seems to be unim-
portantinreactionsofinternalalkenesbecausethemoststable
intermediate tertiary carbenium ion is sterically crowded and
shouldbeveryunreactiveinanadditiontotheinternalalkene.
In contrast, during reaction of 1-alkenes, the formed tertiary
carbenium ion is less crowded, and addition to the 1-alkene
willbeasfastasorevenfasterthanhydridetransferfromthe
ethylaluminum species. Fortunately, reaction conditions could
befound(addingEtSiH)suchthathydridetransfertotheadduct
3
carbenium ion is the fastest trapping reaction which enables
the hydro-alkyl-addition products to be obtained in 47-82% able to perform Wagner-Meerwein rearrangements,30 being
isolated yield (Table 1).
fasterthantheadditionandthehydridetransferreaction.Thus,
Thisbasicreactionmechanismenablesustounderstandthe
2- (12c) and 3-pentyl chloroformate (12l) gave the same ratio
resultsgiveninTable1,entries1-13.Ascanbeexpected,the
of 2- and 3-addition products of 1.3:1, giving evidence that
primarilyformedcarbeniumion(isopropyl,cyclohexyl)isadded
3-pentylcationismorestablethan2-pentylcation(Scheme5).
without regioselectivity to oleic acid (2) and the respective
Reactionsofprimaryalkylchloroformatesgaveexclusively
methylester3(entries2,3,and5).Unfortunately,theaddition
rearranged products with respect to the primary alkyl group
tomethylricinoleate(4)occursaswellwithoutregioselectivity
(Tables2and3).Noprimaryadditionproductswereobserved
(entry 4). Expectedly, high regioselectivity is observed in
in contrast to deaminations of 1-aminoalkanes which yielded
reactionsof1-alkenes(entries9-13)and1-methylcyclohexene
rearrangedandprimaryreactionproductswithwater.301-Propyl
(6) (entry 8). The lowest yields were obtained by reacting
chloroformate (12d) gave the same addition products and
2-methyl-1-undecene(8)becausehydrodimersof8wereformed
comparableyieldsasisopropylchloroformate(12a).Obviously,
in a competitive reaction which could not be fully suppressed
duringtheEtAl Cl -mediateddecompositionof12d,rearrange-
3 2 3
by the addition of Et SiH. That is remarkable because, in the
3 ment of 1-propyl to isopropyl occurs, possibly by concerted
primaryadditionreaction,astabletertiarycationisformedand
1,2-H shift and CO elimination. The following reaction steps
2
direct hydride transfer to this adduct ion gives product 26
togivethefinalproductoccurasoutlinedinthebasicreaction
(Scheme 4). However, a stable tertiary cation is formed by
scheme (Scheme 2). The same applies to the reactions of
(cid:226)-hydrogen transfer from the isopropyl cation as well, and chloroformates 12e-g (Table 2, entries 3-8). The Et Al Cl -
3 2 3
additiontoalkene8followedbyhydridetransfergives,finally,
mediateddecompositionofneopentylchloroformate(12i)gives
thehydrodimer.Thesameconsiderationsapplytoreactionsof
the tert-pentyl cation (Scheme 6), and the Et Al Cl -mediated
3 2 3
1-methylcyclohexene(6).Theminoryieldsofadditionsofbutyl,
decompositionofisobutylchloroformate(12h)bytwocompeti-
pentyl, and hexyl cations may be explained by competitive
tive1,2-shiftsofHandCH givestert-butyland2-butylcation,30
3
(cid:226)-hydrogentransferfromthesecondarycationstocyclohexene
respectively, which are added to the respective alkene.
(5)togiveaninternalalkeneandacyclohexylcationthatadds
It can be assumed from the experimental results that the
tocyclohexene,affordingfinallycylohexylcyclohexane(Table
carbenium ions are fully equilibrated prior the addition to the
2, entries 5-7).
alkene.Thus,reacting2-pentylchloroformate(12c)withalkene
It should be pointed out that the carbocations that are
9(Table1,entry14)and1-pentylchloroformate(12f),aswell
formulatedforconvenienceasfreecarbocationsinschemes2-7
as3-pentylchloroformate(12l)withcyclohexene(5)(Table2,
may exist as ion pairs stabilized by their anionic counterparts
because dichloromethane is neither an ionizing nor a nucleo-
(30) Keating,J.T.;Skell,P.S.InCarboniumIons;Olah,G.A.,Schleyer,P.v.
philic solvent. However, the carbocationic species formed are R.,Eds.;Wiley: NewYork,1970,Vol.II,pp573-653.
10326 J.AM.CHEM.SOC.9VOL.126,NO.33,2004
AlkylationofAlkeneswithEthylaluminumSesquichloride ARTICLES
Scheme6. MechanismoftheReactionofNeopentylChloro- Scheme7. MechanismofReactionsofDi-tert-butylpyrocarbonate
formate(12i)withEthylaluminumSesquichlorideand10-Unde- (52)inthePresenceofEt3Al2Cl3withCyclohexene(5)and
cenoicAcid(9)GivingHydro-AlkylationProducts46and47 Cyclopentene(11)ToGiveAlkylationProducts45/54and55,
Respectively
entry6),gavethesameratioof2-and3-pentyladditionproducts
(Scheme 5). The same applies to 1-hexyl chloroformate, 12g,
whichwasaddedtoalkenes5and9togivetheadditionproducts
inaratioof1:1and1.1:1,respectively(Table2,entries7-8).
In comparison, deamination of 2-aminopentane in water gave
2- and 3-pentanol in a ratio of 3:1.31
Remarkably, a hydro-tert-butyl addition product was only Additionreactionsoftert-alkylcationstocyclopentene(11)
observed by reacting alkenes with a 1,1-dialkyl-substituted aremostremarkable.Reactionwithdi-tert-butylpyrocarbonate
double bond, such as in 8, and with an internal double bond, (52) gave 1,1,2-trimethylcyclohexane (55) (Table 4, entry 5).
such as in 2 and 5, whereas 1-alkene 9 gives the rearranged Nocyclopentanederivativecouldbedetected.Arationalization
product 44 (Table 3, entries 1-3; Table 4, entries 1-4). That of the formation of 55 is given in Scheme 7. Addition of the
canbestraightforwardlyrationalized.Byadditionoftert-butyl tert-butylcationto11yieldsasecondarycyclopentylcation.A
cation to alkene 8, a stable tertiary adduct carbenium ion is 1,2-H shift followed by a concerted 1,2-CH shift and a ring
3
formed, which is reacted with hydride to give product 53. In enlargement gives the most stable endocyclic tert-cyclohexyl
contrast,byadditionto1-alkene9,asecondaryadductcarben- cation and, finally, by hydride transfer, product 55. Ring
ium ion is obtained which can be stabilized by a 1,2-H shift enlargement of 1-ethylcyclopentyl to 1-methylcyclohexyl cat-
andafollowing1,2-CH3shifttogiveatertiarycarbeniumion. ion33andof2-(2-cyclopentyl)propylcationto1,2-dimethylcy-
The following hydride transfer gives, highly selectively and clohexyl cation34 is well known and studied by quantum
preparativelyveryinterestingly,a2,3-dimethylalkylcompound. mechanicalcalculations.35Therespectiveadditionoftert-pentyl
Reacting alkenes containing an internal double bond, tert- cation by reaction with neopentyl chloroformate (12i) analog-
butylatedandrearrangedproductswereobserved.Intheaddition ously gave the isomeric cyclohexane derivatives 50 and 51
step,asecondarycarbeniumadductionisformedfollowedby because of a competitive 1,2-shift of methyl and ethyl in the
1,2-Hshifttogiveatertiarycarbeniumion.Now,theproduct adduct cation (Table 3, entry 6). Interestingly, reaction of
outcomeseemstobecontrolledthermodynamically.Inthecase isopropyl chloroformate (12a) with 11 yielded, as already
of alkene 2, the tert-butylated products 42 and 43 are formed
discussed, isopropylcyclopentane as the major product (Table
preferably. In contrast, in the case of cyclohexene (5), the
1, entry 7). As minor products, cis- and trans-dimethylcyclo-
exocyclic rearranged cation seems to be more stable,32 and a
hexanecouldbedetected,formedclearlybyringenlargement
ratio of [45]:[54] ) 5:1 was observed (Scheme 7).
as described above. These results show that the most stable
Addition of the tert-pentyl cation to alkene 9 occurs as product, carbenium ionic species, are formed, reacting finally
outlinedaboveforthetert-butylcationaddition.Thedifference with the hydride donor.
is that methyl and ethyl can undergo 1,2-shifts competitively,
Afewexampleswerestudiedgivingdiastereomericproducts.
giving two isomers (Scheme 6). The ratio of isomers 46 and
Products 46 and 50 were formed unselectively; whereas the
47wasfoundtobe2.2:1.Additiontocyclohexene(5)yielded
formation of products 18/19 and 24 showed low stereoselec-
analogously the addition products 48 and 49 (Table 3, entries
tivity, giving evidence that the reaction scheme may possibly
4, 5).
be useful in stereoselective synthesis.
(31) Fry,J.L.;Karabatsos,J.J.InCarboniumIons;Olah,G.A.,Schleyer,P.
v.R.,Eds.;Wiley: NewYork,1970,Vol.II,pp521-571. (33) Lenoir,D.;Siehl,H.-U.InHouben-Weyl;GeorgThieme-Verlag: Stuttgart,
(32) Siehl,H.-U.;Vrcek,V;Kronja,O.J.Chem.Soc.,PerkinTrans.22002, 1990,Vol.E19c,p264.
106-113. (34) Vrcek,V.;Siehl,H.-U.;Kronja,O.J.Phys.Org.Chem.2000,13,616-6.
J.AM.CHEM.SOC.9VOL.126,NO.33,2004 10327
ARTICLES BiermannandMetzger
Conclusions triethylsilane (0.58 g, 5 mmol) and EtAlCl (1.24 g, 5 mmol) was
3 2 3
thenaddeddropwiseover1hat-15(cid:176) C,andthemixturewasstirred
Our investigation of the ethylaluminum sesquichloride-
for an additional 1 h at room temperature. Diethyl ether (100 mL),
mediated hydro-alkylation of a very broad variety of alkenes
HO(40mL),and10%HCl,todissolveprecipitatedaluminumsalts,
2
withalkylchloroformatesexhibitingdifferentstructuralfeatures were then added. The organic phase was separated and washed with
clearlyestablishedthescopeofthisverygeneralcationichydro- HO (3 (cid:2) 30 mL). The combined extracts were dried over NaSO,
2 2 4
alkyl addition as a powerful synthetic tool. Some important thesolventwasremovedinvacuo,andtheresiduesofexperiments8,
classesofalkylbranchedalkanes,e.g.,2-methylalkanes,3-me- 10and16weredissolvedinpentaneandfilteredthroughsilicagel60.
thylalkanes, 2,4-dimethylalkanes, 2,3-dimethylalkanes, 2,2,4- After the pentane was evaporated, purification was achieved by
trimethylalkanes, and cyclohexylalkanes, can be generally Kugelrohrdistillation.Theresiduesofexperiments11,12,13,15and
17 were purified by column chromatography using petroleum ether/
synthesizedwithhightomoderateyields.Importantfunctional
EtOAc(7:3).Fractionscontainingthealkylationproductwerecollected,
groups,e.g.,carboxy,ester,andhydroxy,arecompatiblewith
thesolventwasevaporated,andtheresiduedriedat20(cid:176) C/0.01mbar.
the reaction conditions, enabling the selective synthesis of
3.4-Isopropyloctane(13).Thereactionoftrans-4-octene(1)(0.56
carboxylicacids,esters,andalcoholswithabranchedalkylchain
g, 5 mmol) and isopropyl chloroformate (12a) (0.7 g, 5 mmol) was
as given above for the respective alkanes.
carriedoutasdescribed(procedure1)andgave,afterpurificationof
thecrudeproductbyKugelrohrdistillation,0.52g(67%)of 13asa
ExperimentalSection
colorlessoil;n20)1.4239;1HNMR(300.1MHz)(cid:228))0.88(d,J)
D
1.GeneralMethods.Allreactionswereperformedundernitrogen. 6.9 Hz, 6H, CH), 0.94 (m, 6H, CH), 1.09 (m, 2H, CH), 1.32 (m,
3 3 2
Solventsweredriedanddistilledaccordingtostandardprocedures. 8H, CH), 1.74 (m, 1H, 4-H); 13C NMR (75.5 MHz) (cid:228) ) 14.56 and
2
Oleicacidandmethyloleate(newsunflower,82.8%oleicacid,3.6% 14.94(C1andC8),19.52and19.56(CH(CH)),21.25(C7),23.35,
32
stearic acid, 3.5% palmitic acid, 8.4% linoleic acid) and methyl 29.31 (C9), 30.45, 30.63, 33.32, 43.84 (C4); GC/MS (EI), m/z (%)
ricinoleate(80-85%purity)wereobtainedfromCognis.Theamounts 156(3),112(66),71(71),57(100).
ofthestartingolefinsusedinthereactionswerecalculatedbasedon 4.Mixtureof9-IsopropyloctadecanoicAcid(14)and10-Isopro-
100% purity. 10-Undecenoic acid and methyl 10-undecenoate were pyloctadecanoicacid(15).Thereactionofoleicacid(2)(1.41g,4.2
obtainedfromAtochem,andEt3Al2Cl3wasobtainedfromCrompton mmol) and isopropyl chloroformate (12a) or 1-propyl chlorformate
GmbH. 1-Propyl, 1-hexyl, isobutyl, and neopentyl chloroformate, as (12d) (0.7 g, 5 mmol), respectively, was carried out as described
well as 1-octene, trans-4-octene, cyclohexene, cyclopentene, and (procedure 1) and gave, after purification of the crude product by
2-methyl-1-undecene, were purchased from Aldrich and used as columnchromatography,0.99g(73%)and0.97g(71%),respectively,
received. Isopropyl, cyclohexyl, and 1-butyl chloroformate were ofamixtureof14and15((cid:25)1:1)asacorlorlessoil;n19)1.4588.
D
obtained from BASF, and 1-, 2-, and 3-pentyl chloroformate were 5.MixtureofMethyl9-Isopropyloctadecanoate(16)andMethyl
synthezisedasdescribed.36ForcolumnchromatographyMerck60silica 10-Isopropyloctadecanoate (17). The reaction of methyl oleate (3)
gel,70-230mesh,wasused.AnalyticalGCwasperformedonaCarlo (1.48g,4.2mmol)andisopropylchloroformate(12a)(0.7g,5mmol)
Erba GC series 4160 with an FID detector and fused silica capillary wascarriedoutasdescribed(procedure1)andgave,afterpurification
columnDB1,29m.1Hand13CNMRspectrawererecordedinCDCl3 ofthecrudeproductbyKugelrohrdistillation,1.02g(71%)ofamixture
onaBrukerAM300orBrukerAM500spectrometerat20(cid:176) Cusing of16and17((cid:25)1:1)asacolorlessoil;n20)1.4500;1HNMR(500.1
TMS (1H NMR) and CDCl3 ((cid:228) ) 77.0 ppm, 13C NMR) as internal MHz)(cid:228))0.79(d,J)6.6Hz,6H,CHD(CH3)2),0.87(t,J)7.0Hz,
standards. Selected data are given; full 1H and 13C NMR data are 3H,18-H),1.25(m,27H,CH),1.61(m,2H,3-H),1.66(m,1H,9-H),
2
availablefromtheauthorsonrequest.Massspectrawererecordedon 2.29(t,J)7.6,2H,2-H),3.65(s,3H,OCH);13CNMR(125.8MHz)
3
aFinniganMAT212.Allproductswereunambiguouslyidentifiedby (cid:228))14.07(C18),19.17(CH(CH)),22.66(C17),24.94(C3),31.91
32
1Hand13CNMRandbyMS(EI)orGC/MS(EI).Refractiveindices, CH(CH)),34.10(C2),43.69(C9(10)),51.37(OCH),174.29(C1);
32 3
nD,weretakenonaZeiss-Abbe´refractometer.Elementalanalyseswere MS(EI),m/z(%)340(10)[M+],309(2),297(100),265(25);C22H44O2
performed by Mikroanalytisches Labor Beller, D-37004 Go¨ttingen, (340.59)calcd,C77.58,H13.02;found,C77.50,H12.91.
Germany.
6.MixtureofMethyl12-Hydroxy-9-isopropyloctadecanoate(18)
2.SynthesisofAlkylationProducts.2.1.Procedure1(Standard andMethyl12-Hydroxy-10-isopropyloctadecanoate(19).Thereac-
ReactionConditions).Amixtureof5mmoloftherespectivealkene tion of methyl ricinoleate (4) (1.56 g, 4.2 mmol) and isopropyl
and 5 mmol of the alkyl chloroformate, 12, in CH2Cl2 (10 mL) was chloroformate (12a) (0.7 g, 5 mmol) was carried out as described
stirredinaN2atmosphere(1bar)for5minat-15(cid:176) C.Et3Al2Cl3(1.24 (procedure 1) and gave, after purification of the crude product by
g,5mmolfor1,6,and9-11;1.86g,7.5mmolfor2and3,and2.47 Kugelrohr ditillation, 0.9 g (60%) of a mixture of 18 and 19, which
g,10mmolfor4)wasaddeddropwiseover1h(0.5hfor6)at-15 wereformedasmixturesofdiastereomers,respectively,inaratioof
(cid:176) C,andthesolutionwasstirredatroomtemperatureforanadditional 7:1(GC)for18and5:3(GC)for19,asacolorlessoil;n20)1.4605;
D
1h(0.5hfor6).Diethylether(100mL),H2O(40mL),and10%HCl, 1HNMR(500.1MHz)(cid:228))0.82(m,9H,18-H,(CH3)2CH),1.23(m,
todissolveprecipitatedaluminumsalts,werethenadded.Theorganic 22H, CH), 1.37 (m, 4H, 11-H, 13-H), 1.59 (m, 3H, 3-H, 9(10)-H),
phasewasseparatedandwashedwithH2O(3(cid:2)30mL).Thecombined 2.27(t,J2)7.5Hz,2H,2-H),3.55(m,1H,12-H),3.64(s,3H,OCH3);
extractsweredriedoverNa2SO4.Thesolventwasremovedinvacuo. 13C NMR (125.8 MHz) (cid:228) ) 14.02 (C18), 18.14 (CHCH3), 19.05
Purification was achieved by Kugelrohr distillation or column (CHCH),19.24(CHCH),22.57(C17),31.81(CH(CH)),34.05(C2),
3 3 32
chromatography,usingpetroleumether/EtOAc(7:3)aseluent.Fractions 38.32(C9(10)),38.57(C9(10)),39.80(C9(10)),43.80(C9(10)),51.36
containing the alkylation products were collected, the solvent was (OCH),70.11(C12),70.41(C12),72.39(C12),72.44(C12),174.27
evaporated,andtheresiduewasdriedat20(cid:176) C/0.01mbar. (C1);3MS(CI,iso-butane)m/z(%)357(18)[MH+],3.39(100)[MH+
2.2.Procedure2(ModifiedReactionConditionswithAddition -HO];HR-MS(EI)C H O calcd,356.3290;found,356.3293.
2 22 44 3
ofTriethylsilane).Amixtureof5mmoloftherespectivealkeneand
7. Mixture of 9-Cyclohexyloctadecanoic Acid (20) and 10-
of 5 mmol of the alkyl chloroformate, 12, in CHCl (10 mL) was
2 2 CyclohexyloctadecanoicAcid(21).Thereactionofoleicacid(2)(1.41
stirredinaN atmosphere(1bar)for5minat-15(cid:176) C.Amixtureof
2 g, 4.2 mmol) and cyclohexyl chloroformate (12b) (0.81 g, 5 mmol)
wascarriedoutasdescribed(procedure1)andgave,afterpurification
(35) Vrcek,V.;Saunders,M.;Kronja,O.J.Org.Chem.2003,68,1859-1866.
of the crude product by column chromatography, 1.51 g (83%) of a
(36) Petersen,S.;Piepenbrink,H.-F.InHouben-Weyl,4thed.;GeorgThieme-
Verlag: Stuttgart,1952;Vol.8,101-104. mixture of 20 and 21 ((cid:25)1:1) as a pale yellow oil; n20 ) 1.4712; 1H
D
10328 J.AM.CHEM.SOC.9VOL.126,NO.33,2004