Modular Synthesis of α-Substituted Alkenyl Acetals by a Palladium-Catalyzed Suzuki Reaction of α-Haloalkenyl Acetals with Organoboranes

Abstract

A modular and straightforward synthetic strategy for the preparation of α-substituted alkenyl acetals has been developed. α-Haloalkenyl acetals react smoothly with (het)aryl boronic acids, aryl boronates, or B-alkyl-9-borabicyclo[3.3.1]nonanes through Pd-catalyzed Suzuki cross-coupling under mild conditions with good to high yields. This protocol features a broad substrate scope and good functional-group compatibility, and is easily scaled up.

Key words

alkenyl acetals - palladium catalysis - Suzuki reaction - cross-coupling - arylboronic acids - arylation

Publication History

Received: 04 November 2020

Accepted after revision: 25 November 2020

Accepted Manuscript online:
25 November 2020

Article published online:
12 February 2021

• References and Notes

• 1a Miyaura N, Yamada K, Suzuki A. Tetrahedron Lett. 1979; 3437
• 1b Miyaura N, Suzuki A. J. Chem. Soc., Chem. Commun. 1979; 866
• 2 Miyaura N, Suzuki A. Chem. Rev. 1995; 95: 2457

For selected reviews, see:
• 3a Campeau L.-C, Hazari N. Organometallics 2019; 38: 3
• 3b Lennox AJ. J, Lloyd-Jones GC. Chem. Soc. Rev. 2014; 43: 412
• 3c Johansson Seechurn CC. C, Kitching MO, Colacot TJ, Snieckus V. Angew. Chem. Int. Ed. 2012; 51: 5062
• 3d So CM, Kwong FY. Chem. Soc. Rev. 2011; 40: 4963
• 4 For a review, see: Nicolaou KC, Bulger PG, Sarlah D. Angew. Chem. Int. Ed. 2005; 44: 4442
• 5a Ferraboschi P, Reza-Elahi S, Verza E, Santaniello E. Tetrahedron: Asymmetry 1999; 10: 2639
• 5b Coates RM, Hobbs SJ. J. Org. Chem. 1984; 49: 140
• 5c Kagabu S, Mizoguchi S. Synthesis 1996; 372
• 6a Bailey WF, Reed DP, Clark DR, Kapur GN. Org. Lett. 2001; 3: 1865
• 6b Zhang Q, Zhu S.-F, Qiao X.-C, Wang L.-X, Zhou Q.-L. Adv. Synth. Catal. 2008; 350: 1507
• 6c Gu Y, Wu F, Yang J. Adv. Synth. Catal. 2018; 360: 2727
• 7a Crossland I. Org. Synth. 1981; 60: 6
• 7b Song Q.-W, Yu B, Liu A.-H, He Y, Yang Z.-Z, Diao Z.-F, Song Q.-C, Li X.-D, He L.-N. RSC Adv. 2013; 3: 19009
• 8 Cacchi S, Fabrizi G, Moro L, Pace P. Synlett 1997; 1367
• 9 Kang S.-K, Ha Y.-H, Yang H.-Y. J. Chem. Res., Synop. 2002; 282
• 10 Qin L, Ren X, Lu Y, Li Y, Zhou J. Angew. Chem. Int. Ed. 2012; 51: 5915
• 11a Zhang L, Fang Y, Jin X, Guo T, Li R, Li Y, Li X, Ye Q, Luo X, Tian Z. Org. Chem. Front. 2018; 5: 1457
• 11b Zhang L, Fang Y, Jin X, Xu H, Li R, Wu H, Chen B, Zhu Y, Yang Y, Tian Z. Org. Biomol. Chem. 2017; 15: 8985
• 11c Fang Y, Zhang L, Jin X, Li J, Yuan M, Li R, Wang T, Wang T, Hu H, Gu J. Eur. J. Org. Chem. 2016; 1577
• 11d Fang Y, Zhang L, Li J, Jin X, Yuan M, Li R, Wu R, Fang J. Org. Lett. 2015; 17: 798
• 11e Fang Y, Zhang L, Jin X, Li J, Yuan M, Li R, Gao H, Fang J, Liu Y. Synlett 2015; 26: 980
• 11f Yuan M, Fang Y, Zhang L, Jin X, Tao M, Ye Q, Li R, Li J, Zheng H, Gu J. Chin. J. Chem. 2015; 33: 1119
• 11g Fang Y, Yuan M, Zhang J, Zhang L, Jin X, Li R, Li J. Tetrahedron Lett. 2016; 57: 1460
• 12 Martin R, Buchwald SL. Acc. Chem. Res. 2008; 41: 1461
• 13 Jiang M, Feng L, Feng J, Jiao P. Org. Lett. 2017; 19: 2210
• 14a Myers AG, Zheng B, Movassaghi M. J. Org. Chem. 1997; 62: 7507
• 14b Fang Y, Yuan M, Jin X, Zhang L, Li R, Yang S, Fang M. Tetrahedron Lett. 2016; 57: 1368
• 15a Tabatabaeian K, Mamaghani M, Mahmoodi NO, Khorshidi A. Catal. Commun. 2008; 9: 416
• 15b Joarder DD, Gayen S, Sarkar R, Bhattacharya R, Roy S, Maiti DK. J. Org. Chem. 2019; 84: 8468
• 16 (3,3-Diethoxyprop-1-en-2-yl)benzene (3a): Typical Procedure A Schlenk tube equipped with a magnetic stirrer bar was charged with Pd(OAc)₂ (0.9 mg, 0.004 mmol, 2 mol%), XPhos (3.8 mg, 0.008 mmol, 4 mol%), Cs₂CO₃ (163 mg, 0.5 mmol, 2.5 equiv), and PhB(OH)₂ (2a; 48.8 mg, 0.4 mmol, 2 equiv). The tube was then sealed with a cap and degassed by alternating vacuum evacuation and N₂ backfill. A 0.2 M solution of 2-bromo-3,3-diethoxyprop-1-ene (1a; 41.6 mg, 0.2 mmol) in 1,4-dioxane (1 mL) was added to the tube under nitrogen, and the mixture was stirred at 40 °C for 3 h. When the reaction was complete (TLC), the mixture was cooled to r.t., diluted with EtOAc (2 mL), and pushed through a plug of silica gel with EtOAc. The filtrate was concentrated under reduced pressure, and the residue was purified by chromatography [silica gel (300-400 mesh), EtOAc-petroleum ether (1:100)] to give a light-yellow oil; yield: 34.6 mg (84%). ¹H NMR (500 MHz, CDCl₃): δ = 7.53–7.52 (m, 2 H), 7.34–7.28 (m, 3 H), 5.56 (s, 1 H), 5.55 (s, 1 H), 5.25 (s, 1 H), 3.68–3.62 (m, 2 H), 3.58–3.52 (m, 2 H), 1.21 (t, J = 7.1 Hz, 6 H). ¹³C NMR (125 MHz, CDCl₃): δ = 144.9, 138.5, 128.1, 127.6, 126.7, 115.7, 101.8, 61.4, 15.1.