Bases strong bulky

As a practical matter elimination can always be made to occur quantitatively Strong bases especially bulky ones such as tert butoxide ion react even with primary alkyl halides by an E2 process at elevated temperatures The more difficult task is to find condifions fhaf promofe subsfifufion In general fhe besf approach is fo choose condi lions lhal favor fhe 8 2 mechanism—an unhindered subslrale a good nucleophile lhal IS nol slrongly basic and fhe lowesl praclical lemperalure consislenl wilh reasonable reaclion rales... 

Reagent Strong bulky Bronsted base (e.g., Me,CO ) Strong nucleophile... 

However, there is always the possibility of some E2 elimination taking place as well. Neverthless, substitution is usually favoured overelimination, even when using strong bases like HO" or EtO". If E2 elimination of a primary halide is desired, it is best to use a strong bulky base like ferf-butoxide [(CH3)3C-0"]. With a bulky base, the elimination product is favoured over the substitution product since the bulky base experiences more steric hindrance in its approach to the electrophilic carbon than it does to the acidic p-proton. 

Chemoselective E2 eliminations can be carried out with sterically hindered, sufficiently strong bases. Their bulkiness causes them to react with an H atom at the periphery of the molecule rather than at a C atom deep within the molecule. These bases are therefore called nonnucleo-philic bases. The weaker nonnucleophilic bases include the bicyclic amidines DBN (diazabi-cyclononene) and DBU (diazabicycloundecene). These can be used to carry out chemoselective E2 eliminations even starting from primary and secondary alkyl halides and sulfonates (Figure 4.17). 

R-Li (alkyllithium) Methyllithium Butyllithium sec-Butyllithium fert-Butyllithium Strong base Strong nucleophile when R is not bulky. Deprotonation of weak organic acids, E2 eliminations Sn2/Sn2 displacements, addition reactions, addition-elimination reactions... 

El reaction occurs if a strong, bulky base is used. 

The dihydro-1,2-azaboroles 4 <1996CHEC-II(3)753>, 2,5-dihydro-l,2-oxaboroles 14 <20040M5088>, and dihydro-1,2-thiaboroles 19-21 <20000M4681, 20000M4935> can be deprotonated by strong, bulky bases as in Equation (6), the most widely used bases being lithium diisopropylamide (LDA), lithium 2,2,6,6-tetramethylpiperidide (LTMP), and KN(SiMe3)2. 

The regiochemistry of the elimination, if the basic structure is given, can be influenced by the choice of the leaving group and the base. Fluorides yield the Hofmann product preferentially, while iodides afford the Zaitsev pr uct. Strong bulky bases, e.g. KOBu in Bu OH, increase the proportion of Hofmann product. The advantage of the bulky base is lost in DMSO. ... 

E2 reactions are favoured over SN2 reactions by using strong bulky bases (which are poor nucleophiles). 

A primary B and C secondary and D tertiary bromoalkanes, reacting with (a) a good nucleophile that is a moderately weak base (b) a strong, bulky base (c) a good nucleophile that is a moderately strong, nonbulky base (d) like (a), a good but not particularly strongly basic nucleophile and (e) a weak and essentially nonbasic nucleophile. 

A 1-Bromobutane (primary) will give SN2 products, CH3CH2CH2CH2Nu, under all conditions except (b) (E2 with strong bulky base to give CH3CH2CH=CH2) and (e) (no reaction with poor nucleophile). 

E2 The main reaction with strong, bulky bases, such as potassium tert-butoxide. 

NaHMDS was chosen as a strong bulky base for the initial deprotonation of 116. This deprotonation was carried out at —78 °C with stirring for 0.5 h, with the development of a strong yellow colour indicating this step had been successful. This solution was then transferred into a solution of malonate 110 in THF also at -78 °C, and the mixture stirred at -78 °C for 0.5 h. TLC analysis indicated no reaction after this time and so the temperature was increased to —30 °C, to rt., and then further to 50 °C. However stiU no reaction was observed to have occurred, and upon work up both unreacted starting materials were present in the NMR spectrum of the crude reaction mixture as the only components (Scheme 2.13). 

Epoxides are converted to allylic alcohols with nonnucleophilic bases such as lithium diethylamide [LiN(CH2CH3)2]. Draw a stepwise mechanism for the conversion of 1,2-epoxycyclohexane to 2-cyclohexen-1 -ol with this base. Explain why a strong bulky base must be used in this reaction. 

LDA (a Strong, bulky base but a poor nucleophile) is used to form an enolate ion in reactions that require the carbonyl compound to be completely converted to the enolate ion before it reacts with an electrophile. 

RCH2X strong nucleophile strong bulky base Sn2 E2... 

R2CHX strong base and nucleophile strong bulky base weak base and nucleophile Sn2 + E2 E2 SnI + El... 

NaOCOCHs is a good nucleophile and weak base, and substitution is favored. [3] KOC(CH3)3 is a strong, bulky base that reacts by E2 elimination when there is a (3 hydrogen in the alkyl halide. 

No substitution occurs with a strong bulky base and a 3° RX. The C with the leaving group is too crowded for an 3 2 substitution to occur. Elimination occurs instead by an E2 mechanism. 

Although the process is a common one, many reactions in practice give a mixture of products. While we may influence the outcome by using a more or less strong/bulky base, sometimes, the selectivity may still be too poor for practical application. In Figure 10.29, there is only one possible elimination process. 

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