1,2-Bis(chlorodimethylsilyl)ethane can be used as a reagent for the protection of primary amines as their tetramethyldisilylazacyclopentane
or Stabase adducts; used in combination
with zinc to form organozinc carbenoids; electrophilic silylating
reagent.
Protection of Primary Amines.
Few protecting groups exist
for the N,N-diprotection of primary amines. The tetramethyldisilylazacyclopentane
or Stabase adduct (3) is particularly attractive
for this purpose due to its ease of preparation, base stability and
facile removal. This cyclic disilane is easily prepared (eq 1) from
the commercially available title reagent (1).For primary amines
with pKa values between 10 and 11, typical reaction conditions
involve the treatment of a dichloromethane solution of the amine
with (1) in the presence of two equivalents of triethylamine at
room temperature. Subsequent workup with aqueous dihydrogen
phosphate provides (3) in excellent yields.1 Stabase adducts are
quite stable to strongly basic conditions such as n-butyllithium and
s-butyllithium (at ?25°C), lithium diisopropylamide, and Grignard
reagents making it a superb candidate for use in the alkylation
of substrates bearing a primary amine. For example, protected
amino acid derivatives are easily alkylated (eq 2).After formation
of the lithium enolate of the protected ethyl glycinate (4)
under standard conditions, exposure to various alkyl halides or
aldehydes yields alkylation products such as (5).
