George W. Kabalka,' John D. Baker, Jr., and Gary W. Neal Universltv of Tennessee
I
Organoboranes as Alkylating Agents
Organoboranes are playing an increasingly important role in synthetic organic chemistry ( I ) . A number of factors have contributed to the utility of the organohoranes as synthetic intermediates. These include their ready availability and versatile reactivitv. In addition the orranoboranes are unique among organomeiallic reagents in &at functionally substituted oreanohoranes mav readilv be prepared via the hydrohorationof the appropr&tely s"bsti&&l alkenes. Early studies demonstrated the versatility of the organoboranes as reactive intermediates. Utilizing the hydrohoration reaction a wide varietv of alkenes can he functionalized in a stereospecific and regioselective manner (eqn. (1)) (2).(X = -OH, -H, -Br, -NH2, -R, -Hg+, etc.)
We wish to present two hydrohoration-alkylation sequences which clearly demonstrate the synthetic utility of the organohoranes. Each synthesis can he performed in one three-hour lahoratory period. The experiment utilizes stable, commercially available reagents (moderately priced) and standard laboratory glassware. Each reaction involves the preparation of trihexylborane (using l-hexene and horane dimethylsulfide (eqn. (4)) and its reaction with an a,B-unsaturated ketone under free-radical conditions (eqns. (5) and (6)) (3, 10). In the f i s t synthesis, trihexylhorane is reacted with a simple a,p-unsaturated ketone, methyl vinyl ketone to yield 2-decanone (eqn. (5)). In the second synthesis, the organoborane is reacted with p-quinone to yield 2-hexyl-p-hydroquinone (eqn. (6)) (3,lO).
The functionality is dependent, of course, on the reaction conditions (Rx) utilized. Recent develo~mentshave focused on the oreanoboranes as alkylating ageits. This is an extremely exciting area of research due to the fact that the rerio- and stereochemicalintegrity of thealkyl groups in the &anoboranes are normally retained in the alkylation reaction. I t is now known that the organohoranes can transfer one or more of their alkyl suhstituents via two distinct mechanistic pathways. The transfer may occur via a free radical chain reaction (eqn. (2)) (3,4) or via an anionotropic rearrangement (eqn. (3)) (I, 5). Numerous examples of these alkylation reactions have appeared in recent years (2, 6, 7).
R,B
+
M0
2 R-OBK
2
Experimental Authors of current undergraduate organic textbooks have recognized the utility of the organohoranes and have been providing increased coverage of their role in synthesis. Unfortunately, the authors of undergraduate lahoratory manuals have not followed snit. There have been iustifiable reasons for the omission of organohorane reactions in the past: (1) the necessarv horane solutions (BH?.THF) have been somewhat difticult to prepare, requiring the ure of metal hydrides; (2, the burane sdutions have heen difficult to store. reauirine dw. . oxygen-free conditions a t 0°C; (3) many of thk organic sub: strates (methyl vinyl ketone, carbon monoxide, ethyl bromoacetate, etc.) were inconvenient to handle in an underrradnate laboratory. - Recent advances in borane chemistry have altered this situation sirnificantlv. Trialkvlboranes can now be conveniently prepared in an undergraduate lahoratory using the stable, commercially available hydroharating agent borane The borane dimethylsulfide complex dimethylsulfide (8,9). can he transferred in an oxygen atmosphere without significant loss of h y d ~ i d e . ~
-
Reagents All reagents are available from Aldrieh Chemical Company and can be used without further purification. Apparatus .\ standsrd.singlt. necked. 5u0-mlround bottom flask,fitred with a ('la~ren~daprcris empluyd. A reflux nmoruser, iitred with sdvln:: tube 15 atrarhed I., one sldr ui thc Clatsen ndsprrr and n dropping runnel ftttrd wth n as lnlrt t i h e is .lttacned t u rhr urher ' r h ~gas inlet t h e i s n,n,rru tcd minpnsmall piece ofpiari luhlng iniertrd i n t u 3 rhrrrnmnrtrr ndaptrr. Synthesis of Tri-n-hexylborane3 (Hood!) The apparatus is flushed with an inert gas such as nitrogen or carbon dio~ide.~ While continuing the flushing,the borane dimethylsulfide (3.7 ml, 38 mmole) is added to the flask by temporarily removing the condenser. This is fallowed hy the addition of 40 ml of diethyl ether.5The reflux condenser is replaced and the nitrogen flaw 1
To whom correspondence should be addressed. Volume 53. Number 9, September 1976 / 549
discontinued. I-Hexene (14.4ml, 115mmole) is placed in the dropping funnel and added to the horane solution dropwise. The rate of addition should he fast enough to achieve a gentle reflux (an ice-water hath may be used to moderate the reflux rate). After the addition is completed, the solution is gently refluxed for 15 min using a hot water hath.6 The solution is cooled to room temperature and the Claisen adapter is replaced by a distilling head and condenser. The etherdimethylsulfide solvent mixture is distilled from the reaction flask by means of a steam bath (No flame^).^ At the completion of the distillation, the distilling head is again replaced by the Claisen adapter, dropping funnel, and reflux condenser. Synthesis of 2-Decanone The trihexylborane (uido supm) is diluted with 50 ml of diethyl ether. Water (1.8ml,lOOmmole) is added to the flask to destroy any residual hydride. A solution of methyl vinyl ketone (2.6 ml, 31 mmole) (Lachrymator) dissolved in 50 ml of diethyl ether is placed in the dropping funnel. The reaction flaskis warmedon the steam bath (No flames at this point) and the ketone solution added over aperiod of 20 mi". The reaction mixture is refluxed for an additional 20 min after the addition is complete. The reaction mixture is then cooled, extracted with 3 X 45-ml portions of 2 N KOH (to remove the borinic acid byproduct), washed with 2 X 50-ml portions of water, over anhydrous MgSO*. The ether is removed by distillation (steam bath) and the product purified by distillation a t reduced pressure (water aspirator), hp 165-180°C at 140 mm Hg. The yield of 2-decanone is 3.9 g
may he air dried by plncina in n henker w c i l t he next labomtory per i d , rnp6U-:W. Theywid of crude hrxylh\,droquinunr i s 5 3 :l 960 .I." The pruduct may he rerrystallmd from s SwS0 toluene-pentme mirt&, mp 79-80DC Discussion T h e alkylation of a,&unsaturated ketones is representative of a broad spectrum of free-radical chain reactions of organoboranes (3,11,12). T h e reaction with a$-unsaturated ketones c a n h e visualized a s occurring as outlined below. Initiation
+
R,B
trace of 0,
R,B02.
+
R.
' -fO
Propagation
R.
Propagation
"7"' +
/
+
R ~ B+
Synthesis of 3-~exylhydroquinone p-Quinone (3.37 g, 31 mmole) dissolved in 120 ml of ethyl ether is placed in the dropping funnel. The reaction flask, containing the trihexylborane, is warmed on a steam bath and thequinone solution added over a period of 20 min.sAt the completion of the addition, the Claisen adapter is replaced by a distilling head and condenser. The ether is distilled from the reaction flask by means of a steam bath (No flames at this point!). Water (300 ml) is added to the brown liquid remaining in the distilling flask and 150 ml of water isdistilled from the flask using a Bunsen burner. This steam distillation removes the dihexylhorinicaeid (which often collects in the condenser ss a white solid) and any unreaeted quinane. Thedistilling flaskiscoaled in an ice hath and the product collected on a Buehner funnel. The product The reactions must hecarried out in an efficient hood due to the evolution of dimethylsulfide. We have found horane dimethylsulfide to he remarkably stable. We dispense it from a huret fitted only with a drying tube. The student can transfer it via small flasks or vials under atmospheric conditions. The loss of hydride due to oxygen and moisture is insignificant (less than 5%)if the manipulations are carried out quickly (less than 5 min). In an attempt togauge the dangers involved we have "spilled" a few milliliters of horane dimethylsulfide into a large watchglass. I t does not inflame. The reagent slowly reacts with moisture to form a white crusty material. Caution! The borane dimethylsulfideis presumably toxic and laboratory cleanliness should he emphasized. "he products contain approximately 10% of the sec-hexyl derivatives (5-methyl-2-nonanone in the 1st synthesis and 2-[l-methylpentyl]-p-hydroquinone in the 2nd synthesis). This is a cnnsequence of the fact that the hydrohoration reaction is not completely regiospeeifie. The distillation of 2-decanone will yield traces of the solid dihexvlborinic acid (which is not quantitatively removed by the KOH washes) if the distillation temperature is permitted to rise much bevond the hoiline mint of 2-deeanane. ,~~ ' During the hvdroborntion, an mert dry almosphrre ISimpormnt. We fuund srni1.1cylinder d nltn,:rn tu be conwnirnt. Cnrhm di
