Dedicated to my research supervisor Dr. Pinaki S. Bhadury
Introduction
n -Butyllithium (n -BuLi) is one of the most prominent organolithium reagents in the whole of synthetic
chemistry,[1 ]
[2 ]
[3 ] and available as solutions in alkanes such as pentane, hexane, or heptane, which
is usually encountered as a pale yellow solution. It is unstable towards air or moisture
but stable in an atmosphere of nitrogen. It has been widely used in organic reactions,
such as regioselective lithiation reaction,[
4
] reversible metathesis reaction,[
5
] Claisen rearrangement,[
6
] phospho-Fries rearrangement,[
7
] coupling reaction,[
8
] asymmetric deprotonation–electrophilic trapping reaction,[
9
] enantioselective hydroxyalkylation,[
10
] etc. In general, n -butyllithium is commercially available and can also be prepared readily by the reaction
of 1-bromobutane or 1-chlorobutane with Li metal (Scheme [1 ]).[
11
] An overview of the usage of n -BuLi in organic synthesis is presented below.
Scheme 1
(A) Fort and co-workers described an efficient method for the synthesis of polysubstituted
furo[2,3-c ]pyridines via successive regioselective lithiations, using n -BuLi or [n -BuLi/LiDMAE] as base. For each step the products were obtained in moderate to excellent
yields.[
4
]
(B) Bailey et al. reported mild and highly efficient experimental conditions for the
reversible metathesis reaction known as the lithium–halogen exchange. The reaction
products of 1-bromo-4-tert -butylbenzene with n -BuLi at 0 °C are obtained quantitative in heptane containing a small quantity of
THF. Particularly, nettlesome side reactions, including coupling of aryllithium with
the co-generated alkyl halide and formation of a benzyne intermediate via ortho-metalation
of the aryl halide, are effectively avoided.[
5
]
(C) Upon treatment with n -BuLi, a variety of allyl 1,1-dichlorovinyl ethers undergo rearrangement to furnish
high yields of γ,δ-unsaturated esters after alcohol addition. A potential advantage
of this method over other variants of the Claisen rearrangement is the ability to
add a variety of alcohol nucleophiles to the proposed ketene intermediate, allowing
the one-pot preparation of diverse esters of γ,δ-unsaturated carboxylic acids with
high stereoselectivity.[
6
]
(D) n -BuLi together with i -Pr2 NH has been used in the preparation of bifunctional BINOL ligands bearing phosphine
oxides [P(=O)R2 ], phosphonates [P(=O)(OR)2 ], or phosphoramides [P(=O)(NR2 )2 ] at the 3,3′-positions via a phospho-Fries rearrangement as key step. This method
has an advantage with regard to yield and purification in comparison with a coupling
method that uses halide compounds, expensive diphenylphosphine oxide [Ph2 P(=O)H], and palladium or nickel catalysts.[
7
]
(E) Tarselli and Micalizio described a successful procedure for the coupling of aliphatic
imines with allylic and allenic alkoxides enabled by a unique reactivity profile of
Ti(IV) isopropoxide/n -BuLi compared to well-known Ti(IV) isopropoxide/RMgX systems. This coupling proceeds
with moderate to excellent yields.[
8
]
(F) An enantioselective hydroxyalkylation of o -tolualdehyde and 3-aminotetrahydrofurans (or 3-aminopyrrolidines, 3-aminotetrahydrothiophens)
in the presence of n -BuLi and lithium amides gives the target product 1-o -tolylpentan-1-ol in good yield and moderate ee.[
10
]
(G) The highly pyramidalized alkene pentacyclo-[4.3.0.02,4 .03,8 .05,7 ]non-4-ene was successfully synthesized with n -BuLi via dehalogenation of vicinal dihalides. The method has proven to be reliable
for the synthesis of a variety of strained alkenes.[
12
]
(H) Luliński et al. found that lithiated benzonitriles can be generated in high yields
from reactions of bromobenzonitriles with n- BuLi in THF under standard cryogenic conditions (ca. –70 °C, even up to –60 °C). The
reverse addition mode is employed to reduce significantly side reactions.[
13
]
