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

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

References and Notes

• For examples, see:
• 1a Saha G. Basu MK. Kim S. Jung Y. Adiyaman Y. Powell WS. Fitzgerald GA. Rokach J. Tetrahedron Lett.  1999,  40:  7179 
• 1b Crimmins MT. Choy AL. J. Am. Chem. Soc.  1999,  121:  5653 
• 1c Paquette LA. Braun A. Tetrahedron Lett.  1997,  38:  5119 
• 1d Roush WR. J. Org. Chem.  1991,  56:  4151 
• 1e Ahmar M. Bloch R. Mandville G. Romain I. Tetrahedron Lett.  1992,  33:  2501 
• 2a Bachmann WE. Horwitz JP. Warzynshi RJ. J. Am. Chem. Soc.  1953,  75:  3268 
• 2b Serramedan D. Marc F. Pereyre M. Filliatre C. Chabardes P. Delmond B. Tetrahedron Lett.  1992,  33:  4457 
• 2c Marc F. Soulet B. Serramedan D. Delmond B. Tetrahedron  1994,  50:  3381 
• 3a Hertweck C. Boland W. J. Org. Chem.  2000,  65:  2458 
• 3b Bideau FL. Gilloir F. Nilsson Y. Aubert C. Malacria M. Tetrahedron  1996,  52:  7487 
• 3c Wipf P. Xu W. J. Org. Chem.  1993,  53:  825 
• 4 For an alternative to the use of β,γ-unsaturated aldehydes, see: Hughes G. Lautens M. Wen C. Org. Lett.  2000,  2:  107 
• Racemic allylation and crotylation:
• 5a Lautens M. Ouellet SG. Raeppel S. Angew. Chem. Int. Ed.  2000,  39:  4079 
• Enantioselective allylation:
• 5b Lautens M. Maddess ML. Sauer ELO. Ouellet SG. Org. Lett.  2002,  4:  83 
• Racemic and enantioselective propargylation:
• 5c Maddess ML. Lautens M. Org. Lett.  2005,  7:  3557 
• 6 Racherla US. Brown HC. J. Org. Chem.  1991,  56:  401 
• 7a Brown HC. Bhat KS. J. Am. Chem. Soc.  1986,  108:  293 
• 7b Brown HC. Bhat KS. Randad RS. J. Org. Chem.  1989,  54:  1570 
• 7c Brown HC. Bhat KS. J. Am. Chem. Soc.  1986,  108:  5919 
• 7d For a review, see: Ramachandran PV. Aldrichimica Acta  2002,  35:  23 
• 8 Fujita K. Schlosser M. Helv. Chim. Acta  1982,  65:  1258 
• 9 Jadhav PK. Bhat KS. Perumal PT. Brown HC.
  J. Org. Chem.  1986,  51:  432 
• 10 Brown HC. Sinclair JA. J. Organomet. Chem.  1977,  131:  163 
• 12a Paterson I. Goodman JM. Lister MA. Schumann RC. McClure CK. Norcross RD. Tetrahedron  1990,  46:  4663 
• 12b Paterson I. Lister MA. Tetrahedron Lett.  1988,  29:  585 
• 12c Paterson I. Lister MA. McClure CK. Tetrahedron Lett.  1986,  27:  4787 
• 14 Herold T. Hoffmann RW. Angew. Chem., Int. Ed. Engl.  1978,  17:  768 
• Boron:
• 15a Roush WR. Stereoselective Synthesis, In Methods of Organic Chemistry (Houben-Weyl)  21st. ed., Vol. 3:  Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. Thieme; Stuttgart: 1966.  p.1410-1486  
• Titanium:
• 15b Hoppe D. Stereoselective Synthesis, In Methods of Organic Chemistry (Houben-Weyl)   21st ed., Vol. 3:  Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. Thieme; Stuttgart: 1966.  p.1551-1583  
• 15c Burgos CH. Canales E. Matos K. Soderquist JA. J. Am. Chem. Soc.  2005,  127:  8044 
• Silicon:
• 15d Wang Z. Wand D. Sui X. Chem. Commun.  1996,  2261 
• 15e Kubota K. Leighton JL. Angew. Chem. Int. Ed.  2003,  48:  946 
• 15f Hackman BM. Lombardi PJ. Leighton JL. Org. Lett.  2004,  6:  4375 
• 15g Zyang X. Houk KN. Leighton JL. Angew. Chem. Int. Ed.  2005,  44:  938 
• 15h Masse CE. Panek JS. Chem. Rev.  1995,  95:  1293 
• Tin:
• 15i Nishida M. Tozawa T. Yamada K. Mukaiyama T. Chem. Lett.  1996,  1125 
• 15j Yamada K. Tozawa T. Nishida M. Mukaiyama T. Bull. Chem. Soc. Jpn.  1997,  70:  2301 
• 15k Jephcote VJ. Pratt AJ. Thomas EJ. J. Chem. Soc., Perkin Trans. 1  1989,  1529 
• 17 McCubbin JA. Maddess ML. Lautens M. Org. Lett.  2006,  8:  2993 

11

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

13

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.

16

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

18

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.

19

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).

20

See Supporting Information.