Download (direct link):
slr or MeU/THF (1) 78°C (2) "ds"
The enethiolates (2) present interesting aspects. Some are mentioned below (see  for a discussion and appropriate references):
• They have good thermal stability. No significant decomposition was observed by warming them up to room temperature.
• Under kinetic conditions the enethiolates (2) of cis geometry are formed preferentially and are configurationally stable.
• They are ambident nucleophiles. Attacks from both carbon or sulfur occurred in their reactions with electrophiles, but selectivity was often observed and some new procedures for carbon-carbon bond formation could be developed.
ium enethiolates react rapidly and at low temperature with aldehydes afford good yields of p-hydroxydithioesters [120, 331]. This reaction
“ I) LDA/THF. -78°C
IJ -------------------------». r2
Me SR1 u) RzCHO, -78°C ©
ociated with the use of the dithioesler group as an acyl anion equivalent allows two successive electrophilic additions on two vicinal carbons of the starting dithioester, which appears as a cPd1 synthon:
Î Î ñí2- c=o
The potential of this sequence was applied in Meyers’s total synthesis of antibiotic maytansinoids such as (-)-maysine .
3-10 fragment (with 7-OH and 9-CO protected)
The accompanying scheme shows how ethyl dithioacetate was incorporated (C8 and C9) in the elaboration of the sought after 3-10 fragment of a convergent synthesis, allowing introduction of the aldehydic function (CIO) while affording (C9) a suitably protected carbonyl group (for the building of the cyclic urethane in the last stage of synthesis).
a 5 min period and stirring maintained for 15-20 min. Triethylamine (6.9*> ml, 50 mmol) was added dropwise and the reaction mixture stirred for 5 min at —50°C and for 10 min at +25°C, then poured into water, acidified (1% aqueous HC1) and extracted with dichloromethane. The organic lay^r was washed with saturated aqueous sodium chloride, dried (MgSO„) and the solvent evaporated under reduced pressure. The (B-oxodithioester was purified by liquid chromatography (eluent: heptane/ethyl acetate).
For R1 = Me, R2 = Ph the aldol was obtained in an 82% yield and the P* oxodithioester in an 80% yield.
For R* = Ph and R2 = Me the yields of the two steps were, respectively-50 and 90%.
From  with permission.
It is of note that only this last compound is obtained by base condensation of carbon disulfide with the ketone PhCH.COEt. Moi‘e generally the selective preparations of the two rcgioisomers corresponding to the exchange of the R1 and R2 groups is of interest, although tl'e reaction failed for R1 = H (the dimer of the a-unsaturated dithioester formed by dehydration of the aldol was isolated instead).
A few aldol reactions have been reported for thionoesters , bllt apparently none for thioketones so far.
4.2.5 Michael addition
The addition reaction of enethiolates towards Michael acceptors has bet'11 investigated (for reviews, see [120, 362]). It was established that lithiui" dithioester enethiolates undergo regioselective 1,4-addition with a wiJc
variety of a-unsaturated ketones around -50°C, under aprotic conditions, yielding good to excellent yields of 5-oxoalkanedithioates [332, 363, 364]. This behaviour of dithioester lithium enethiolates as soft nucleophiles is particularly valuable in view of the known 1.2 addition of lithium enolates of carboxylic esters with enones under similar conditions.
i) LDA/THF. -78°C, 5 min Î
S -98°C to -10°C. 15-30 min
sr2 * bK ill) NH4C1. h2o ^
ill) NH4C1. h2o
Michael addition of lithium enethiolates
To a solution of LDA (40 mmol) in THF (200ml) cooled at -45°C, methyl dithioacctate (3.92ml, 40mmol) was added dropwise. The yellow colour rapidly disappeared. The mixture was stirred for 5 min. 2-Cyclohexenone (3.92 ml, 40 mmol) was then added dropwise. A yellow colour appeared. The resulting mixture was stirred for 15 min. An aqueous solution of ammonium chloride was added and the mixture partitioned between ether and brine. The organic layer was washed with brine, dried with magnesium sulfate and concentrated. Methyl (cyclohexanone-3-yl)dithioacetate (3) (6.75g, 33.4mmol, 83%) was isolated by flash chromatography on silica gel using cyclohexane/ethyl acetate (9:1) as the eluent.
From  with permission.
With reactive Michael partners the reaction had to be run at lower temperatures (—98°C for methyl vinyl ketone for a 30% yield), and with less reactive ones the temperature had to be raised for the addition to occur (-10°C for 3-methylcyclohexenone for a 52% yield).