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Asymmetric Synthesis of Cyclobutanone via Lewis Acid Catalyzed Tandem Cyclopropanation/Semi-Pinacol Rearrangement Su Yong Shim, Yuna Choi, and Do Hyun Ryu J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b06835 • Publication Date (Web): 08 Aug 2018 Downloaded from http://pubs.acs.org on August 8, 2018
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Journal of the American Chemical Society
Asymmetric Synthesis of Cyclobutanone via Lewis Acid Catalyzed Tandem Cyclopropanation/Semi-Pinacol Rearrangement Su Yong Shim,† Yuna Choi,† and Do Hyun Ryu*,†,‡ †
Department of Chemistry, Sungkyunkwan University, Suwon 16419, Korea
‡
School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022, China
Supporting Information Placeholder ABSTRACT: Chiral Lewis acid catalyzed asymmetric formation of cyclobutanones from α-silyloxyacroleins and α-alkyl or α-aryl diazoesters has been developed. In the presence of a chiral oxazaoborolidinium ion catalyst, various αsilyloxycyclobutanones possessing a chiral β-quaternary center were synthesized in high yield (up to 91%) with excellent enantioand diastereoselectivity (up to 98% ee and up to > 20 : 1 dr) through tandem cyclopropanation/semi-pinacol rearrangement. The synthetic potential of this method was illustrated by conversion of the product to various cyclic compounds such as γlactone, cyclobutanol, and cyclopentanone.
Cyclobutane derivatives, small and strained ring compounds, have drawn increasing attention because they constitute valuable building blocks or target molecules in medicinal chemistry and are found in numerous natural products.1 Among various synthetic approaches, enantioselective formation of cyclobutanones has become a powerful method because they can be easily converted to many valuable cyclic or acyclic compounds through ring opening or ring expansion reactions due to their inherent ring strain.2 Cobalt catalyzed enantioselective intramolecular hydroacylation3a and palladium catalyzed asymmetric allylic alkylation3b were reported to afford chiral cyclobutanones possessing an αquaternary center. Alternatively, 1,2-alkyl migration of cyclopropanol (semi-pinacol rearrangement4) into an olefin moiety5-7 has emerged as an efficient route to cyclobutanones (Scheme 1A). Recently, the Alexakis group reported a halogenation-induced semi-pinacol rearrangement of 1-vinyl cyclopropanol to afford βhalo spirocyclobutanones with a chiral phosphoric acid (CPA) catalyst.8 The Toste and Trost groups have developed transition metal-catalyzed enantioselective ring expansion of olefinic cyclopropanols with gold9a and palladium9b catalysts, respectively, to provide chiral α-vinyl cyclobutanones. Although semi-pinacol rearrangements of cyclopropanes involving a 1,2-alkyl shift into a carbonyl moiety to afford α-hydroxy or α-silyloxycyclobutanones have been known for decades,10 a catalytic asymmetric version of this reaction has not been reported to date (Scheme 1B). Scheme 1. Synthesis of cyclobutanones through semi-pinacol rearrangement of cyclopropanes.
Recently, catalytic asymmetric cyclopropanations11a,b and enantioselective formation of 2,5-dihydrooxepines11c were developed by our group using α-alkyl, aryl, or vinyl diazoesters and substituted acroleins in the presence of a chiral oxazaborolidinium ion12 (COBI) as a Lewis acid catalyst. Inspired by these encouraging results, we discerned that there was substantial feasibility of using COBI catalysis to prepare chiral 1-formyl-1silyloxycyclopropanes (1), which could be rearranged into chiral α-silyloxycyclobutanones13 (2) through semi-pinacol rearrangement (Scheme 1C). To the best of our knowledge, the ring expansion of cyclopropane 1 to cyclobutanone 2 via 1,2-alkyl migration into a carbonyl group activated by Lewis acid has not been reported to date, although there are some reports of rearrangements of olefinic5-9 or alkynic9c cyclopropanols via π-acidic transition metal catalyst or organocatalyst. Herein, we describe a chiral Lewis acid catalyzed enantioselective formation of cyclobutanones with two adjacent stereogenic centers including a β-quaternary carbon14 through tandem cyclopropanation/semi-pinacol rearrangement starting from α-silyloxyacroleins and diazoesters. Table 1. Optimization of conditions for enantioselective synthesis of cyclobutanonea
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entry
X
2
cat
solvent
yield of 2 (%)b
dr of 2c
ee of 2 (%)d
1
TBS
2a
4a
CH2Cl2
78
2.8:1
0
2
TBS
2a
4a
PhMe
79
2.5:1
3
3
TBS
2a
4a
EtCN
70
2.0:1
50
4
TBS
2a
4b
EtCN
73
2.3:1
30
5
TBS
2a
4c
EtCN
72
2.8:1
55
6
TBS
2a
4d
EtCN
69
3.0:1
69
7e
TIPS
2b
4d
EtCN
