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Synlett 2011(19): 2857-2861  
DOI: 10.1055/s-0031-1289565
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Allylation and Crotylation of in situ Generated β,γ-Unsaturated Aldehydes

J. Adam McCubbin, Matthew L. Maddess, Mark Lautens*
Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6, Canada
Fax: +1(416)9468185; e-Mail: mlautens@chem.utoronto.ca;
Further Information

Publication History

Received 11 August 2011
Publication Date:
31 October 2011 (online)

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Abstract

β,γ-Unsaturated aldehydes generated in situ by treatment of 2-vinyloxiranes with a catalytic amount of Sc(OTf)3 are effectively trapped by ring-strained allyl- and crotylsilane reagents to afford bishomoallylic alcohols as single diastereomers in high enantiomeric excess.

Key words

vinyloxiranes - enantioselective crotylation - silanes - Lewis acid catalysis - rearrangement reaction

11

Diminished but still substantial yields of the bishomoallylic alcohol were observed.

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The bright yellow color of metalated 2-butene is observed to fade after addition of approximately 0.5 equiv of TfOB(Ipc)2 while for MeOB(Ipc)2 the yellow color persists until a full equivalent has been added.

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The absolute stereochemistry of the product [(S)-8b] was established by comparison of HPLC traces with material obtained from enantioselective Brown allylation of 6b.5b This assigned configuration is consistent with that observed by Leighton et al.¹5e

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The following procedure is representative for the allylation reaction. See Supporting Information for full characteri-zation data of all products.
Synthesis of ( S )-8b A 25 mL round-bottom flask was flame dried under a stream of nitrogen and allowed to cool to r.t. To this was added 3 (250 mg, 0.45 mmol) and Et2O (3.0 mL). The mixture was cooled to 0 ˚C, and Sc(OTf)3 (14.8 mg, 0.03 mmol) was added followed by the slow addition of 6b (44 mg, 0.3 mmol) over 3 h as a solution in Et2O (2.0 mL). After the addition was complete the reaction was stirred for 2 h at 0 ˚C, and then an equal volume of aq HCl (1 N) was added, and the mixture stirred for 10 min at r.t. The reaction mixture was diluted with H2O and transferred to a separatory funnel with Et2O. The organic layer was isolated, and the aqueous layer was extracted with Et2O (2×). The combined organic layers were dried with MgSO4, filtered, concentrated in vacuo, and the crude residue was purified by flash chroma-tography (5-10% EtOAc-hexane) to afford the desired product (S)-8b as a colorless oil (yield 73%). ¹H NMR (300 MHz, CDCl3): δ = 7.38-7.35 (m, 2 H), 7.33-7.28 (m, 2 H), 7.24-7.19 (m, 1 H), 6.48 (d, J = 15.9 Hz, 1 H), 6.24 (ddd, J = 15.9, 7.4, 7.4 Hz, 1 H), 5.92-5.81 (m, 1 H), 5.19-5.13 (m, 2 H), 3.84-3.74 (m, 1 H), 2.50-2.21 (m, 4 H), 1.81 (d, J = 3.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 137.5, 134.8, 133.3, 128.7, 127.5 126.3, 126.3, 118.4 70.4, 41.6, 40.7. HPLC [CHIRALCEL OD, 1 mL/min, hexane-2-PrOH (95:5), 30 ˚C, 1 µL injection]: t R1 = 14.4 min (minor), t R2 = 17.7 min (major);96% ee.

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The following procedure is representative for the crotylation reaction. See Supporting Information for full characterization data of all products.
Synthesis of ( R , S )-7b To a 25 mL round-bottom flask was added Leightons’ reagent [(E)-4, 256 mg, 0.45 mmol] and toluene (3.0 mL). The mixture was cooled to 0 ˚C, and Sc(OTf)3 (14.8 mg, 0.03 mmol) was added followed by the slow addition of 6b (44 mg, 0.3 mmol) over 3 h as a solution in toluene (2.0 mL). After 2 h at 0 ˚C, an equal volume of aq HCl (1 N) was added, and the mixture was stirred for 10 min at r.t. The reaction mixture was diluted with H2O and transferred to a separatory funnel with Et2O. The organic layer was isolated, and the aqueous layer was extracted with Et2O (2×), the combined organic layers were dried with MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (10% EtOAc-hexane) to afford the desired product (R,S)-7b as a colorless oil (yield 51%). ¹H NMR (400 MHz, CDCl3): δ = 7.38-7.35 (m, 2 H), 7.32-7.27 (m, 2 H), 7.23-7.18 (tt, J = 4.3, 1.8 Hz, 1 H), 6.51-6.45 (d, J = 15.9 Hz, 1 H), 6.31-6.23 (ddd, J = 15.8, 7.8, 6.7 Hz, 1 H), 5.86-5.76 (ddd, J = 16.6, 11.0, 8.2 Hz, 1 H), 5.16-5.15 (s, 1 H), 5.14-5.10 (ddd, J = 8.2, 1.9, 0.9 Hz, 1 H), 3.59-3.48 (ddt, J = 7.8, 5.9, 3.7 Hz, 1 H), 2.52-2.45 (dddd, J = 14.2, 6.6, 3.9, 1.5 Hz, 1 H), 1.74-1.71 (d, J = 3.4 Hz, 1 H), 1.10-1.07 (d, J = 6.9 Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 140.0, 137.3, 132.7, 128.5, 127.1, 126.5, 126.0, 116.3, 74.2, 43.5, 38.0, 16.2. FTIR (neat): ν = 3392, 2971, 2930, 1640, 1598, 1495, 1450, 1418, 1028, 999, 966, 915, 745, 693 cm-¹. HRMS (EI): m/z calcd for C14H18O [M+] 202.1358; found: 202.1363. HPLC [CHIRACEL OD, 1 mL/min, hexane-2-PrOH (95:5), 30 ˚C, 1 µL injection]: t R1 = 13.1 min, t R2 = 14.3 min (major); 92% ee; [α]D ²0 +29.7 (c 0.024, CHCl3).

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See Supporting Information.