Communication Cite This: J. Am. Chem. Soc. 2018, 140, 11184−11188
pubs.acs.org/JACS
Asymmetric Synthesis of Cyclobutanone via Lewis Acid Catalyzed Tandem Cyclopropanation/Semipinacol 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
‡
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S Supporting Information *
Scheme 1. Synthesis of Cyclobutanones through Semipinacol Rearrangement of Cyclopropanes
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 oxazaborolidinium ion catalyst, various α-silyloxycyclobutanones possessing a chiral βquaternary center were synthesized in high yield (up to 91%) with excellent enantio- and diastereoselectivity (up to 98% ee and up to >20:1 dr) through tandem cyclopropanation/semipinacol rearrangement. The synthetic potential of this method was illustrated by conversion of the product to various cyclic compounds such as γ-lactone, cyclobutanol, and cyclopentanone.
C
yclobutane 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 (semipinacol rearrangement4) into an olefin moiety5−7 has emerged as an efficient route to cyclobutanones (Scheme 1A). Recently, the Alexakis group reported a halogenation-induced semipinacol rearrangement of 1-vinyl cyclopropanol to afford β-halo 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 semipinacol 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). 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. © 2018 American Chemical Society
Inspired by these encouraging results, we discerned that there was substantial feasibility of using COBI catalysis to prepare chiral 1-formyl-1-silyloxycyclopropanes (1), which could be rearranged into chiral α-silyloxycyclobutanones13 (2) through semipinacol 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/semipinacol rearrangement starting from α-silyloxyacroleins and diazoesters. Initially, enantioselective formation of the cyclobutanone from reaction of α-tert-butyldimethylsilyloxyacrolein and phenyl diazoester in the presence of 20 mol % COBI catalyst 4 was examined (Table 1). When the reaction was carried out in dichloromethane or toluene, α-silyloxycyclobutanone 2a was formed through tandem cyclopropanation/semipinacol rearrangement of C1 in low diastereomeric ratio and ee (path a, entries 1 and 2). The alternative cyclobutanone formed by 1,2alkyl shift of C2 substituted with two hydrogen atoms was not observed under these reaction conditions. In addition, 20% of the diazo carbon-inserted product12d,15 3a was formed as a Received: June 29, 2018 Published: August 8, 2018 11184
DOI: 10.1021/jacs.8b06835 J. Am. Chem. Soc. 2018, 140, 11184−11188
Communication
Journal of the American Chemical Society
of the 2-fluorophenyl diazoester arising from both steric and electronic effects. An aryl diazoester with the electronwithdrawing 4-cyano group afforded cyclobutanone 2m in 73% yield with high ee, albeit with low diastereoselectivity. Various p-tolyl diazoesters possessing different ester substituents were examined, and all reacted well to furnish the corresponding cyclobutanones 2n−q in high yield with good to excellent enantio- and diastereoselectivity. It is notable that this method was also successfully applied to alkyl diazoesters to generate chiral cyclobutanones 2r−2u. Sterically bulkier diazo tert-butyl or 1-adamantyl esters gave higher yields than the corresponding diazo ethyl ester16 with nearly complete control of enantio- and diastereoselectivity. The absolute configuration of 2r was unambiguously determined by X-ray analysis, and the configurations of all other products 2 were assigned accordingly. In addition, NOE analyses of β-phenylcyclobutanone 2c and β-ethylcyclobutanone 2r confirmed that both aryland alkyl-substituted cyclobutanone have same relative configurations. To demonstrate the synthetic utility of this methodology, further chemical transformations of the resulting optically active 2-(triethylsilyloxy)cyclobutanone 2n were carried out (Scheme 2). Reduction with NaBH4 proceeded effectively to afford a single diastereomeric17 cyclobutanol 5. Ring expansion by Baeyer−Villiger oxidation successfully provided β-quaternary γ-lactone 6. Enantioselective synthesis of β-quaternary γlactones is known to be challenging due to the difficulty of construction of an all-carbon quaternary stereocenter at a remote position from the carbonyl group.18 Interestingly, the Lewis acid catalyzed carbonyl addition of (trimethylsilyl)diazomethane in dichloromethane at low temperature gave a single diastereomeric17 α-silyl cyclopentanone 719,20 in good yield through Tiffeneau−Demjanov type ring expansion.21 This regioselective ring expansion was achieved by preferred migration of the less substituted −CH2 group in accordance with the accepted order of migratory aptitudes for diazoalkyl insertion.22 In order to verify the semipinacol rearrangement of cyclopropane intermediate 1 to cyclobutanone 2 and its enantioselectivity, we carried out control experiments (Scheme 3). After 24 h under the optimized conditions, trans-1i23 and cyclobutanone 2i were both obtained. A prolonged reaction time under the same conditions gave cyclobutanone 2i as the sole product with a trace amount of trans-1i, indicating that cyclopropane 1i was converted to cyclobutanone 2i under the Lewis acidic conditions (Scheme 3A). Exposure of isolated trans-1i (93% ee) to similar reaction conditions (COBI catalyst 4d in propionitrile at −78 °C) gave cyclobutanone 2i with retention of enantioselectivity (93% ee) with some unidentified decomposition impurities (Scheme 3B). These results demonstrate that cyclopropane intermediate 1 was initially formed and was subsequently converted into cyclobutanone 2 under Lewis acidic conditions through the stereoselective semipinacol rearrangement in a concerted manner.24 Based on this preliminary mechanistic investigation, the observed stereochemistry for the catalytic enantioselective formation of cyclobutanones with COBI catalyst 4d can be rationalized on the basis of the transition state model shown in Figure 1. The coordination mode of acrolein to catalyst 4d and the enantioselective cyclopropanation with diazoester are the same as have previously been observed for the enantioselective cyclopropanation11a,b and formation of 2,5-dihydrooxepines.11c
Table 1. Optimization of Conditions for Enantioselective Synthesis of Cyclobutanonea
entry
X
2
cat
solvent
yield of 2 (%)b
dr of 2c
ee of 2 (%)d
1 2 3 4 5 6 7e 8 9f
TBS TBS TBS TBS TBS TBS TIPS TES TES
2a 2a 2a 2a 2a 2a 2b 2c 2c
4a 4a 4a 4b 4c 4d 4d 4d 4d
CH2Cl2 PhMe EtCN EtCN EtCN EtCN EtCN EtCN EtCN
78 79 70 73 72 69
