Propargylic lithium derivatives

Several equilibria are involved in this reaction, as shown by B NMR. The metalation-hydroboration of acetylides leads to 1,3-diols. A possible sequence of transformations for the reaction of H3B-THF with propargylic lithium derivative is . 

A mixture of 0.40 mol of propargyl chloride and 150ml of dry diethyl ether was cooled at -90°C (liquid nitrogen bath) and a solution of 0.40 mol of ethyl-lithium (note 1) in about 350 ml of diethyl ether (see Exp. 1) was added with vigorous stirring and occasional cooling (note 2). The temperature of the reaction mixture was kept between -70 and -90°C. The formation of the lithium derivative proceeded almost instantaneously, so that the solution obtained could be used directly after the addition of the ethyl 1ithium, which was carried out in 15-20 min. This lithium acetylide solution is very unstable and must be kept below -60°C. 

Methyl 4-chloro-2-butynoate has been prepared in 54% yield by treatment of 4-chloro-2-butynoic acid with 10% sulfuric acid in methanol. 4-Chloro-2-butynoic (chlorotetrolic) acid has been prepared in 40% yield by chromic acid oxidation of 4-chloro-2-butyn-l-ol (the latter obtained 1n 45% yield by the reaction of 2-butyne-l, 4-diol with thlonyl chloride) or in 85% yield by treatment of the lithium derivative of propargyl chloride with carbon... 

Each vinyl metal reagent was prepared by thermodynamic hydrostannylation of the corresponding alkyne.41 42 The simpler lithium derivative 165 R = CH2SMe came from the protected propargyl alcohol 167. 

Total synthesis of a-santalol.2 a-Santalol (7) has been synthesized from (—)-ir-bromotricyclene (1) by essentially the same procedure used previously by Corey and Kirst for the synthesis of trans,frans-farnesol (2, 240-241). The starting material was converted into the terminal acetylene (2) by reaction with lithio-1-trimethylsilylpropyne followed by desilylation (2, 239-240). This was converted into the propargylic alcohol (3) by way of the lithium derivative by reaction with paraformaldehyde. /run.v-Hydroaluruination was then effected by treatment with H-buty(lithium followed by diisobutylaluminum hydride. Treatment with iodine... 

Propargylic organoboranes derived from the corresponding lithium reagents react with aldehydes and certain ketones with high regioselectivity to give trimethylsilyl-substituted a-allenic alcohols (Scheme... 

The main use of the title reagent is as a precursor of the lithium derivative. l,3-Bis(triisopropylsilyl)propyne is cleanly lithiated by treatment with 1 equiv of n-butyllithium in THF at —20°C (15 min) to what is probably an equilibrium mixture of propargylic and allenic species (1) and (2) (eq 1). The bulky triisopropylsilyl (TIPS) group serves as a controlling group in the addition of (1/2) to electrophiles. 

Several helical polycyclic aromatic hydrocarbons bearing aryl substituents at the most sterically hindered position were synthesized in an efficient three-step cascade reaction. The initial benzannulated enediynes were synthesized by the reaction of appropriate lithium acetylenides with an aryl-rert-butyl ketone. This was followed by reduction of the resultant acetylenic propargyl type alcohol with triethylsilicon hydride. This method turned out to be particularly successful for the synthesis of helical molecules. The reaction of ketones 3.588 and 3.590 with the lithium derivative of l-ethynyl-2-(2-penylethynyl)benzene 3.545 or related binaphthyl derivative followed by reduction and three-step sequence of cascade reactions led to polycyclic aromatic compounds 3.589 and 3.591, respectively, in a good yield (Scheme 3.48) [294, 295]. 

The alkynylation of estrone methyl ether with the lithium, sodium and potassium derivatives of propargyl alcohol, 3-butyn-l-ol, and propargyl aldehyde diethyl acetal in pyridine and dioxane has been studied by Miller. Every combination of alkali metal and alkyne tried, but one, gives the 17a-alkylated products (65a), (65c) and (65d). The exception is alkynylation with the potassium derivative of propargyl aldehyde diethyl acetal in pyridine at room temperature, which produces a mixture of epimeric 17-(3, 3 -diethoxy-T-propynyl) derivatives. The rate of alkynylation of estrone methyl ether depends on the structure of the alkyne and proceeds in the order propar-gylaldehyde diethyl acetal > 3-butyn-l-ol > propargyl alcohol. The reactivity of the alkali metal salts is in the order potassium > sodium > lithium. 

The reaction of propargylic chiral acetals with a catalytic copper reagent (RMgX/5% CuX) provides the expected alkoxy allenes in quantitative yield (Table 3)61. The diastereomeric excess is highly dependent on the size of the ring of the acetal and on the type of substituents it contains. The best diastereomeric excess is 85% with the acetal derived from cyclooctanediol. The use of lithium dimethylcuprate results in 1,2-addition lo the triple bond and the resulting lithium alkenyl cuprate bearing a cyclic acetal does not eliminate even at reflux temperature ( + 35°C). 

The bromoallene (-)-kumausallene (62) was isolated in 1983 from the red alga Laurencia nipponica Yamada [64a], The synthesis of the racemic natural product by Overman and co-workers once again employed the SN2 -substitution of a propargyl mesylate with lithium dibromocuprate (Scheme 18.22) [79]. Thus, starting from the unsymmetrically substituted 2,6-dioxabicyclo[3.3.0]octane derivative 69, the first side chain was introduced by Swern oxidation and subsequent Sakurai reaction with the allylsilane 70. The resulting alcohol 71 was protected and the second side chain was attached via diastereoselective addition of a titanium acetylide. The synthesis was concluded by the introduction of two bromine atoms anti-selective S -substitution of the bulky propargyl mesylate 72 was followed by Appel bromination (tetrabromo-methane-triphenylphosphine) of the alcohol derived from deprotection of the bromoallene 73. 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

Treatment of the propargylic alcohol 144, readily prepared from condensation between benzophenone (143) and the lithium acetylide 101, with thionyl chloride promoted a sequence of reactions with an initial formation of the chlorosulfite 145 followed by an SNi reaction to produce in situ the chlorinated and the benzannulated enyne-allene 146 (Scheme 20.30) [62], A spontaneous Schmittel cyclization then generated the biradical 147, which in turn underwent a radical-radical coupling to form the formal [4+ 2]-cycloaddition product 148 and subsequently, after a prototropic rearrangement, 149. The chloride 149 is prone to hydrolysis to give the corresponding 11 H-bcnzo h fluoren-ll-ol 150 in 85% overall yield from 144. Several other llff-benzo[fc]fluoren-ll-ols were likewise synthesized from benzophenone derivatives. 

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