PDF icon PDF herunterladen
Synlett 2008(14): 2183-2187  
DOI: 10.1055/s-2008-1078011
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

The Conversion of Carbonyl Compounds into Pentadienylamines by a Julia-Kocienski Olefination Procedure

Reyhan Bastin, Mélanie Liron, Richard J. K. Taylor*
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK
Fax: +44(1904)434523; e-Mail: rjkt@york.ac.uk;
Weitere Informationen

Publikationsverlauf

Received 23 June 2008
Publikationsdatum:
31. Juli 2008 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik
Preview

Abstract

Julia-Kocienski olefination has been successfully employed to convert carbonyl compounds into the corresponding Boc-protected 1,3-pentadienyl amines in a C4N homologation process. Good to excellent yields are achieved in THF using MHMDS as base to deprotonate the precursor 1-phenyl-1H-tetrazol-5-ylsulfone reagent. The nature of the metallic countercation dramatically affects the stereoselectivity of the newly formed alkene: good levels of 2E,4E-stereoselectivity are achieved using KHMDS whereas LiHMDS gives a predominance of the 2E,4Z-dienyl product.

Key words

1,3-pentadienyl amines - modified Julia olefination - alkenes - 1-phenyl-1H-tetrazol-5-yl sulfones

14

Preparation of tert -Butyl ( E )-4-(1-Phenyl-1 H -tetrazol-5-ylsulfonyl)but-2-enyl Carbamate (11) To a solution of the sulfide 10 (7 g, 15.6 mmol) and Mo7O24 (NH4)6˙4H2O (5.8 g, 4.7 mmol) in MeOH (130 mL) was added 30% aq H2O2 (48.3 mL, 468 mmol) at r.t. The solution was stirred for 1 h, and then sat. aq Na2S2O7 solution was added to quench the excess of peroxide. After a stirring for 45 min at r.t., the reaction mixture was extracted with EtOAc (3 × 100 mL), dried (NaSO4), and concentrated in vacuo; purification by silica flash column chromatography (PE-EtOAc, 1:1) gave the title sulfone 11 (5.6 g, 95%) as a white solid, mp 86 ˚C; R f  = 0.56 (PE-EtOAc, 1:1). ¹H NMR (400 MHz, CDCl3): δ = 1.43 (s, 9 H, t-Bu), 3.77 (m, 2 H, CH2-1), 4.41 (d, J = 7.5 Hz, 2 H, CH2-4), 4.63 (br s, 1 H, NH), 5.29-6.04 (m, 1 H, H-2), 6.00 (dt, J = 15.0, 7.5 Hz, 1 H, H-3), 7.57-7.60 (m, 5 H, Ar). ¹³C NMR (100 MHz, CDCl3): δ = 28.7, 42.2, 59.5, 81.5, 114.5, 125.5, 130.0, 131.8, 133.3, 141.1, 153.4, 155.9. IR (neat): νmax = 3356, 2978, 1709, 1502, 1347, 1249, 1155 cm-¹. HRMS: m/z calcd for C16H21N5O4S [MH+]: 380.13925; found (CI): 380.1392 (0.1 ppm error).

16

The Julia-Kocienski olefination is normally trans-selective due to the kinetically controlled and irreversible addition of metallated PT-sulfones to aldehydes preferentially generating anti-β-alkoxysulfones, which then undergo Smile rearrangement. [¹0] [¹¹] In the present study, it would appear that LiHMDS preferentially generates syn-β-alkoxysulfones resulting in a predominance of the E,Z-adducts. The reasons for this unexpected switch are not fully understood at the present time but further studies are in progress to shed light on this interesting observation.

17

Preparation of 1-[ N -( tert -Butoxycarbonyl)amino]-5-phenylpenta-2,4-diene (12)
To as stirred solution of PT-sulfone 11 (45 mg, 0.12 mmol, 1.2 equiv) in THF (1.4 mL) was added LiHMDS (0.26 mL 1.0 M in THF, 0.26 mmol, 2.55 equiv), or KHMDS (0.52 mL, 0.5 M in toluene, 0.26 mmol, 2.55 equiv), at -78 ˚C. In the KHMDS case, 18-crown-6 (34 mg, 0.13 mmol, 1.2 equiv) was also present at the outset. After 1.5 h at the same temperature, the orange mixture was added to benzaldehyde (10.6 mg, 0.1 mmol, 1.0 equiv) in THF (0.9 mL) at -78 ˚C via cannula. The mixture was stirred at -78 ˚C for 1.5 h and then for 1 h at r.t. After quenching with brine (3 mL) and stirring at r.t. for 10 min, the aqueous layer was extracted with EtOAc (3 × 8 mL). The combined organic phases were dried over MgSO4 and concentrated in vacuo. Purification was performed via flash chromatography on SiO2 using mixtures of PE and EtOAc as eluent to afford the product alkenes as mixtures of their 2E,4E/2E,4Z isomers (ratio was determined by ¹H NMR spectroscopy).
Using KHMDS
72% (2E,4E/2E,4Z = 72:28); NMR data for major isomer 12 E,E were comparable to those published.8 Using LiHMDS
72% (2E,4E/2E,4Z = 13:87) as a pale yellow solid, R f  = 0.71 (PE-EtOAc, 4:1); mp 42 ˚C. ¹H NMR (400 MHz, CDCl3; major isomer): δ = 1.43 (s, 9 H, t-Bu), 3.81 (m, 2 H, H-1), 4.58 (br s, 1 H, NH), 5.84 (dt, 1 H, J = 15.0, 5.5 Hz, H-2), 6.23 (t, 1 H, J = 11.6 Hz, H-4), 6.23 (t, 1 H, J = 11.5 Hz,
H-4), 6.42 (d, 1 H, J = 11.5 Hz, H-5), 6.69 (dddd, J = 15.0, 11.5, 2.5, 1.5 Hz, 1 H, H-3), 7.36-7.25 (m, 5 H, Ar). ¹³C NMR (100 MHz, CDCl3; major isomer): δ = 28.1, 42.2, 81.5, 127.9, 128.5, 128.7, 129.4, 129.6, 130.9, 132.9, 137.6, 156.1. IR (neat): νmax = 3318, 2978, 1677, 1531, 1365, 1275, 1166, 995 cm-¹. HRMS: m/z calcd for C16H21NNaO2 [MNa]+: 282.1470; found: 282.1465 (3.5 ppm error)].

18

All novel compounds were fully characterised (sometimes as E,E/E,Z mixtures) including confirmation by high-field NMR and HRMS.