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DOI: 10.1055/s-0029-1219542
An 1,2-Elimination Approach to the Enantioselective Synthesis of 1,3-Disubstituted Linear Allenes
Publication History
Publication Date:
23 February 2010 (online)
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Abstract
The construction of 1,3-disubstituted allene skeleton, which is present in many natural allenes, via an i-PrMgBr-mediated elimination of optically active 3-acetoxy-2-iodo-prop-1-ene derviatives is exemplified through the enantioselective total synthesis of two bioactive natural allenes.
Key words
alkynes - carbanions - elimination - halides - natural products
- Supporting Information for this article is available online:
- Supporting Information
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The substrate utilized in this work was conveniently derived by a Novezyme 435 resolution of the racemic propargylic alcohol. For details, see the Supporting Information.
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References and Notes
For clarity, synthesis of 6a-c is given in the Supporting Information.
9Although i-PrMgBr-mediated elimination of sulfoxides are known (cf. ref. 4b,c), it has never been utilized (to our knowledge) for elimination of α-acetoxyalkenyl halides.
11Lower level of functional-group tolerance is also a major concern here, although the simultaneous cleavage of the terminal Ac protecting group is beneficial in this synthesis.
15All attempts to separate the enantiomers of 14 by chiral HPLC failed.
16Unlike sulfoxides, there is no stereogenic center in iodide. No loss of stereogenic centers occurred with the elimination of the halides.
17
Representative
Procedures
Conversion of 6a into
7
A solution of 6a (150 mg,
0.30 mmol) in dry THF (2 mL) was added dropwise via a syringe to
a solution of i-PrMgBr (2 M, in Et2O,
0.9 mL, 1.8 mmol) in dry THF (5 mL) stirred at -78 ˚C
under argon. After completion of the addition, the stirring was
continued at -60 ˚C for 2.5 h. Aqueous sat. NH4Cl
was added. The mixture was extracted with Et2O (50 mL),
washed with H2O and brine before being dried over anhyd
Na2SO4. Removal of the solvent by rotary evaporation and
column chromatography (PE-EtOAc, 100:1) on silica gel gave
allene 7 as a colorless oil (84 mg, 0.28
mmol, 93%) along with recovered 6a (6
mg, 0.012 mmol, 4%).
Data
for 7
[α]D
²7 -33.7 (c 0.9, CHCl3). ¹H
NMR (300 MHz, CDCl3):
δ = 5.28-5.20
(m, 2 H), 4.54 (dd, J = 5.8,
2.8 Hz, 2 H), 3.62 (t, J = 6.4
Hz, 2 H), 2.07 (s, 3 H), 2.10-2.02 (m, 2 H), 1.54 (quint, J = 7.3 Hz,
2 H), 1.48 (quint, J = 7.1
Hz, 2 H), 0.90 (s, 9 H), 0.05 (s, 6 H). ¹³C
NMR (75 MHz, CDCl3): δ = 205.4, 170.8,
92.8, 86.9, 62.90, 62.87, 32.1, 28.1, 25.9, 25.3, 21.0, 18.3, -5.3.
FT-IR (film): 2955, 2930, 2858, 1963, 1744, 1227, 1103 cm-¹.
ESI-MS: m/z = 321.1 [M + Na]+. HRMS
(MALDI): m/z calcd for C16H30SiO3Na [M + Na]+: 321.1856;
found: 321.1863.