Letter pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Addition−Rearrangement of Ketenes with Lithium N-tertButanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α‑Hydroxycarboxylic Acid Derivatives Peng-Ju Ma,‡ Fan Tang,‡ Yun Yao,† and Chong-Dao Lu*,†,‡ †
School of Chemical Science and Technology, Yunnan University, Kunming 650091, China Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi 830011, China
‡
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S Supporting Information *
ABSTRACT: Addition of the lithium salts of chiral Nsubstituted tert-butanesulfinamides to ketenes and subsequent silylation initiates stereoselective [2,3]-rearrangement, which affords enantioenriched α,α-disubstituted α-sulfenyloxy carboxamides through a reaction that faithfully transfers the absolute stereochemistry of the lithiated sulfinylamides to the α-carbon of the amide products. This addition−rearrangement can be performed together with ketene formation from acyl chloride in a single flask, providing a new and practical synthetic route to α-hydroxycarboxylic acid derivatives. Scheme 1. Asymmetric Synthesis of α-Oxygenated Carboxylic Acid Derivatives from Ketenes
nantioenriched α-hydroxycarboxylic acid derivatives are important structural units in a range of biologically relevant molecules and also serve as useful precursors in organic synthesis.1 A straightforward path to these compounds is asymmetric C−O bond formation at the α-position of acid derivatives using suitable oxygen sources. This approach has been well developed for enantioselective α-oxygen−functionalization of α-unbranched2 and some α-branched acid derivatives, primarily β-keto esters3 and cyclic carboxylic acid derivatives.4 In contrast, asymmetric α-oxygen−functionalization of common acyclic α,α-disubstituted carbonyls is challenging. This reflects the difficulty with which these compounds form the corresponding stereodefined enolates5 as well as the sometimes poor enantio-discrimination between the re and si faces of these enolates.6 Nevertheless, Davis6 and coworkers achieved some success in such functionalizations using double-asymmetric induction involving diastereoselective oxidation of chiral acyclic, polysubstituted enolates with chirality-matched camphorylsulfonyl oxaziridines. Subsequently, several examples of enantioselective construction of tertiary α-hydroxy carbonyls7 via oxidation of stereodefined acyclic enolates or their analogues have been reported.8−11 Enantioselective O,N-bifunctionalizations of ketenes12 have recently been developed for asymmetric synthesis of α-hydroxy carboxylic amide derivatives.13 Using chiral nucleophilic catalysts, disubstituted ketenes react with nitrosoarene to form enantioenriched 1,2-oxazetidin-3-ones,14 in which the presence of an ortho electron-withdrawing group (CF3) on the nitrosoarene is required for good regioselectivity and diastereocontrol (Scheme 1a). In addition, [3 + 2] cycloaddition of disubstituted ketenes with oxaziridines proceeds via Lewis base catalysis to give oxazolin-4-one derivatives with high enantioselectivities (Scheme 1b).15 In both of these
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© XXXX American Chemical Society
protocols, only aryl alkyl ketenes have been examined for simultaneous formation of C−O and amide C−N bonds, and some of these substrates suffer from low yields15 and poor enantioselectivities.14a We hypothesized that disubstituted ketenes could be efficiently O,N-bifunctionalized using a different approach. Our previous studies demonstrated highly stereoselective [2,3]-sigmatropic rearrangement of O-silyl N-tert-butanesulfinReceived: May 2, 2019
A
DOI: 10.1021/acs.orglett.9b01555 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
substituted tert-butanesulfinamides to disubstituted ketenes, followed by silylation, might give fully substituted O-silylated enolates, which in turn might undergo rearrangement to give tertiary α-sulfenyloxy carboxamides (Scheme 1c). This addition−rearrangement is particularly appealing because of the low molecular weight of Ellman’s tert-butanesulfinamide and the commercial availability of its R and S enantiomers on a kilogram scale at low cost.16 Initially, we examined the addition−rearrangement using phenyl ethyl ketene (2a), the most commonly used disubstituted ketene substrate. N-Lithiation of N-p-methoxyphenyl (RS)-tert-butanesulfinamide (1a) with n-butyllithium at −78 °C was followed by introduction of ketene 2a and chlorotrimethylsilane at −78 °C. Keeping the reaction mixture at −78 °C for 1.5 h led to formation of α-sulfenyloxy carboxamide 3a in 69% yield with excellent enantioselectivity (97.5:2.5 er), together with a small amount (∼13%) of acyl NtBS amide 4a (Scheme 2, entry 1). Elevating the reaction temperature accelerated silylation−rearrangement while preserving excellent enantioselectivity (entries 2 and 3). At 0 °C, the reaction was complete within 30 min, affording the desired product 3a in 77% yield with 96.5:3.5 er (entry 3). The addition−protonation product 4a was obtained in 85% isolated yield with ∼3:1 dr when the reaction of 1a and 2a was quenched with an aqueous solution of ammonium chloride rather than TMSCl.19 This indicates that the chiral sulfinyl
Scheme 2. Initial Results of Addition−Rearrangement of Lithiated tert-Butanesulfinamide with Ketene
yl (N-tBS) N,O-ketene aminals to α-sulfenyloxy carboxamides. In this rearrangement, chiral information was transferred from the sulfur atom in the sulfinyl group to the α-position in the amide products.16 Consequently, Ellman’s tert-butanesulfinamide,17 commonly used as a chiral ammonia equivalent, works well as a latent chiral hydroxyl group. We envisaged that azaMislow−Evans rearrangement18 could lead to O,N-bifunctionalization of disubstituted ketenes: addition of lithiated NTable 1. Substrate Scopea
entry
sulfinyl amide (R)
ketene (Ar, R′)
product
yieldb (%)
erc
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21f
1a (PMP) 1b (Ph) 1c (4-MeC6H4) 1d (3-MeC6H4) 1e (2-MeC6H4) 1f (4-FC6H4) 1g (2-naphthyl) 1h (4-MeSC6H4) 1i (4-MeO2CC6H4) 1j (Bn) 1k (nBu) 1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) ent-1a (PMP)
2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2a (Ph, Et) 2b (Ph, Me) 2c (Ph, iPr) 2d (Ph, cyclopentyl) 2e (4-MeC6H4, Et) 2f (3-MeC6H4, Et) 2g (2-MeC6H4, Et) 2h (4-FC6H4, Et) 2i (4-ClC6H4, Et) 2j (PMP, Et) ent-2a (Ph, Et)
3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 3k 3l 3m 3n 3o 3p 3q 3r 3s 3t ent-3a
77 (77)d 77 61 80 84 57 83 78 56 79 66 76 77 80 77 75 23 64 68 74 74
97:3 (97.5:2.5)d 99:1 98.5:1.5 99:1 99:1 99:1 99:1 97.5:2.5 98.5:1.5 87:13 79.5:20.5 97.5:2.5 92:8 95.5:4.5 97:3 97.5:2.5 82.5:17.5 99:1 98:2 97:3 4.5:95.5
Reaction conditions: 1 (0.40 mmol) and nBuLi (0.48 mmol) were stirred in anhydrous THF (4.0 mL) at −78 °C for 15 min before addition of ketene (0.60 mmol). After the mixture was maintained at −78 °C for 15 min, chlorotrimethylsilane (0.80 mmol) was added at −78 °C, and the reaction mixture was then warmed to 0 °C and stirred for 0.5 h before quenching with a saturated solution of NH4Cl. bIsolated yield after silica gel chromatography. cEnantiomeric ratios were determined using HPLC and a chiral stationary phase. dOn a 1.4 g scale. fThe (S)-enantiomer of Ntert-butanesulfinamide was used. a
B
DOI: 10.1021/acs.orglett.9b01555 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters Table 2. Synthesis of α,α-Disubstituted α-Sulfenyloxy Carboxamides using Acyl Chlorides as Starting Materialsa
entry
sulfinyl amine (R)
1 2 3
1a (PMP) 1a (PMP) 1a (PMP)
4 5
1a (PMP) 1a (PMP)
6 7 8 9 10
1a (PMP) 1a (PMP) 1a (PMP) 1a (PMP) 1e (2-MeC6H4)
acid chloride (RL, RS) 5a (Ph, Et) 5b (Ph, Me) 5c (4-MeC6H4, Et) 5d (4-FC6H4, Et) 5e (4-ClC6H4, Et) 5f (Ph, nBu) 5g (iPr, Me) 5h (nBu, Me) 5i (Et, Me) 5i (Et, Me)
product
yieldb (%)
erc
3a 3l 3o
73 72 64
96:4 98:2 95:5
3r 3s
61 65
96:4 97.5:2.5
3u 3v 3w 3x 3y
67 37 74 78 63
94.5:5.5 89.5:10.5 81:19 75:25 73:27
In contrast, use of N-benzylsulfinamide (3j) dramatically reduced enantioselectivity (entry 10, 87:13 er), and using sulfinamides bearing less hindered linear alkyl groups on the nitrogen atom reduced enantioselectivity even further (entry 11, 79.5:20.5 er). A range of aryl alkyl disubstituted ketenes 3b−j were used to react with lithiated sulfinamide 1a to construct enantioenriched α,α-disubstituted α-hydroxycarboxylic amides 3l−t (entries 12−20). Ketenes containing linear or branched aliphatic groups such as methyl (entry 12), isopropyl (entry 13), and cyclopentyl (entry 14) were suitable substrates, as were aryl ethyl ketenes bearing phenyl groups with methyl (ortho, meta, or para), halogen, or methoxy substitutions (entries 15−20). Most of these reactions showed good yields and excellent enantioselectivities. An exception was the reaction of ortho-substituted aryl ketene 2g (entry 17), for which the yield was only 23% and the er was only 82.5:17.5. The low yield was attributed to the formation of a substantial amount of uncharacterized byproducts, but the reasons for the relatively low stereocontrol remain unclear. This approach for O,N-bifunctionalization of ketenes proved robust and was easily scaled up to 1 g without loss of yield or enantioselectivity (Table 1, entry 1). It also allowed easy preparation of both enantiomers of α-tertiary α-hydroxyl amides with high enantiopurity when the corresponding enantiomers of tert-butanesulfinamide were used (Table 1, entries 1 and 21). Preparing the pure ketenes usually involves several tedious operations, including filtration, concentration, and highvacuum distillation under an inert atmosphere.22 Therefore, we examined whether we could use a crude ketene solution directly, which we generated by mixing acyl chlorides and triethylamine in THF. We found that using 3 equiv of αbranched acyl chlorides and 6 equiv of triethylamine gave the desired products in yields and enantiomeric ratios comparable to those obtained using the corresponding purified ketenes (entry 1 in Table 2 vs entry 1 in Table 1, entry 2 in Table 2 vs entry 12 in Table 1, entry 3 in Table 2 vs entry 15 in Table 1, entry 4 in Table 2 vs entry 18 in Table 1, and entry 5 in Table 2 vs entry 19 in Table 1). In particular, this one-pot reaction starting from acyl chloride was applicable for ketenes bearing two linear alkyl groups (entries 7−10), which are rarely used in organic synthesis.23 The moderate stereocontrol observed with ketenes bearing two linear alkyl groups is not entirely surprising, since the two aliphatic groups do not differ enough in bulkiness to generate stereodefined enolate intermediates during addition of lithiated N-tBS sulfinamide. Extending the reaction to common α-linear acid chloride such as propionyl chloride is not feasible. Common monosubstituted ketenes generated from the corresponding α-linear acid chlorides are often formed in the presence of reaction partners in order to capture the ketenes in situ as soon as they formed, which is not applicable in our addition−rearrangement process. Treating tertiary α-sulfenyloxy carboxamide 3a with thiophile P(OMe)3 at room temperature efficiently cleaved the S−O bond24 to afford the corresponding α-hydroxy amide 6 (Scheme 3). Heating the mixture of amide 6 and KOH in ethylene glycol resulted in formation of tertiary α-hydroxycarboxylic acid 7.25 Comparison of the optical rotation of synthesized 7 with the literature26 indicated an absolute configuration of R. During addition−rearrangement, lithiated (RS)-tert-butanesulfinamide generates a stereocenter in the R configuration, which can be rationalized by postulating the rearrangement of
a
Reaction conditions: 5 (1.2 mmol), Et3N (2.4 mmol), lithiated amide (0.4 mmol), and chlorotrimethylsilane (3.6 mmol) were used. b Isolated yield after silica gel chromatography. cEnantiomeric ratios were determined using HPLC and a chiral stationary phase.
Scheme 3. Manipulations of α-Sulfenyloxy Carboxamide 3a and Assignment of Absolute Configuration
Scheme 4. Rationalization of Observed Absolute Stereochemistry
group in the enolate intermediate does not provide good stereocontrol during enolate protonation, which is consistent with the poor 1,4-asymmetric induction observed in reactions of ketenes with optically active amines.20,21 Next we examined the substrate scope of diastereoselective addition−rearrangement of ketenes with chiral lithium N-tertbutanesulfinamide (Table 1). N-tert-Butanesulfinamides bearing diverse N-aryl substitutions (R = Ar) smoothly underwent a cascade of lithiation−addition−silylation rearrangement to give the corresponding α-sulfenyloxy carboxamides 3a−i (entries 1−9) in good yields (56−84%) with excellent enantioselectivities (96.5:3.5−99:1 er). The cascade was compatible with ortho-, meta-, and para-substituted aryl groups. C
DOI: 10.1021/acs.orglett.9b01555 Org. Lett. XXXX, XXX, XXX−XXX
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(4) (a) Sano, D.; Nagata, K.; Itoh, T. Org. Lett. 2008, 10, 1593− 1595. (b) Yang, Y.; Moinodeen, F.; Chin, W.; Ma, T.; Jiang, Z.; Tan, C. H. Org. Lett. 2012, 14, 4762−4765. (5) For selected examples of acyclic stereocontrol of fully substituted enolates, see: (a) Manthorpe, J. M.; Gleason, J. L. J. Am. Chem. Soc. 2001, 123, 2091−2092. (b) Qin, Y.-C.; Stivala, C. E.; Zakarian, A. Angew. Chem., Int. Ed. 2007, 46, 7466−7469. (c) Kummer, D. A.; Chain, W. J.; Morales, M. R.; Quiroga, O.; Myers, A. G. J. Am. Chem. Soc. 2008, 130, 13231−13233. (d) Morales, M. R.; Mellem, K. T.; Myers, A. G. Angew. Chem., Int. Ed. 2012, 51, 4568−4571. (e) Minko, Y.; Pasco, M.; Lercher, L.; Botoshansky, M.; Marek, I. Nature 2012, 490, 522−526. (f) Minko, Y.; Marek, I. Chem. Commun. 2014, 50, 12597−12611. See also references cited therein. (6) Davis, F.; Ulatowski, T. G.; Haque, M. S. J. Org. Chem. 1987, 52, 5288−5290. (7) For recent examples of asymmetric synthesis of α,α-disubstituted α-hydroxy carboxylic acid derivatives from alkylation or rearrangement of enolates derived from 2-substituted 2-methoxyacetic acids, see: (a) Yu, K.; Lu, P.; Jackson, J. J.; Nguyen, T. D.; Alvarado, J.; Stivala, C. E.; Ma, Y.; Mack, K. A.; Hayton, T. W.; Collum, D. B.; Zakarian, A. J. Am. Chem. Soc. 2017, 139, 527−533. (b) Ooi, T.; Fukumoto, K.; Maruoka, K. Angew. Chem., Int. Ed. 2006, 45, 3839− 3842. (c) Podunavac, M.; Lacharity, J. J.; Jones, K. E.; Zakarian, A. Org. Lett. 2018, 20, 4867−4870. See also references cited therein. (8) For a recent example involving stereoselective oxidation of chiral auxiliary-containing polysubstituted silyl ketene aminals generated from carbometalation−oxidation−silylation of ynamides, see: Huang, J. Q.; Nairoukh, Z.; Marek, I. Eur. J. Org. Chem. 2018, 2018, 614−618. (9) For asymmetric organocatalytic α-oxygenation−functionalization of α-branched aldehydes, see: (a) Demoulin, N.; Lifchits, O.; List, B. Tetrahedron 2012, 68, 7568−7574. (b) Witten, M. R.; Jacobsen, E. N. Org. Lett. 2015, 17, 2772−2775. For early examples of enantioselective organocatalytic α-oxidation of aldehydes or ketones, see: (c) Brown, S. P.; Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808−10809. (d) Sundén, H.; Engqvist, M.; Casas, J.; Ibrahem, I.; Córdova, A. Angew. Chem., Int. Ed. 2004, 43, 6532−6535. (10) For asymmetric dihydroxylation of substituted enol derivatives, see: (a) Debergh, J. R.; Spivey, K. M.; Ready, J. M. J. Am. Chem. Soc. 2008, 130, 7828−7829. (b) Gourdet, B.; Lam, H. W. Angew. Chem., Int. Ed. 2010, 49, 8733−8737. (11) For phase-transfer-catalyzed enantioselective α-hydroxylation of acyclic ketones, see: Sim, S.-B. D.; Wang, M.; Zhao, Y. ACS Catal. 2015, 5, 3609−3612. (12) For reviews of ketenes, see: (a) Seikaly, H. R.; Tidwell, T. T. Tetrahedron 1986, 42, 2587−2613. (b) Paull, D. H.; Weatherwax, A.; Lectka, T. Tetrahedron 2009, 65, 6771−6803. (c) Allen, A. D.; Tidwell, T. T. Chem. Rev. 2013, 113, 7287−7342. (13) For asymmetric synthesis of secondary α-oxygenated carboxylic acid derivatives from ketene intermediates, see: (a) Bekele, T.; Shah, M. H.; Wolfer, J.; Abraham, C. J.; Weatherwax, A.; Lectka, T. J. Am. Chem. Soc. 2006, 128, 1810−1811. (b) Abraham, C. J.; Paull, D. H.; Bekele, T.; Scerba, M. T.; Dudding, T.; Lectka, T. A. J. Am. Chem. Soc. 2008, 130, 17085−17094. (c) Shao, P.-L.; Chen, X.-Y.; Sun, L.-H.; Ye, S. Tetrahedron Lett. 2010, 51, 2316−2318. (14) (a) Dochnahl, M.; Fu, G. C. Angew. Chem., Int. Ed. 2009, 48, 2391−2393. (b) Wang, T.; Huang, X.-L.; Ye, S. Org. Biomol. Chem. 2010, 8, 5007−5011. (15) Shao, P.-L.; Chen, X.-Y.; Ye, S. Angew. Chem., Int. Ed. 2010, 49, 8412−8416. (16) Tang, F.; Yao, Y.; Xu, Y.-J.; Lu, C.-D. Angew. Chem., Int. Ed. 2018, 57, 15583−15586. (17) For reviews, see: (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984−995. (b) Robak, M. T.; Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600−3740. (18) (a) Rojas, C. M. In Molecular Rearrangements in Organic Synthesis; Rojas, C. M., Ed.; John Wiley & Sons: Hoboken, NJ, 2016; pp 569−625. (b) Colomer, I.; Velado, M.; Fernández de la Pradilla, R.; Viso, V. Chem. Rev. 2017, 117, 14201−14243.
O-silylated cis-enolate via an exo transition state (Scheme 4).16,27 The cis-enolate forms preferentially to minimize steric interaction between the bulky N-substituted sulfinamide group [tBS(R)N > OSiMe3] and the bulkyl Ar group (Ar > R) at the α-position in the cis-enolate. Replacing the Ar group with a linear alkyl group makes the R and alkyl groups sterically similar, reducing the ratio of cis- to trans-enolate and thereby the enantiomeric ratio for the corresponding rearrangement products (Table 2, entries 8−10). In summary, we have developed an efficient method to construct α-tertiary α-hydroxy acid derivatives. The process involves addition of N-lithiated chiral tert-butanesulfinamide to disubstituted ketene, followed by O-silylation. Stereoselective aza-Mislow−Evans rearrangement allows enantioselective installation of a sulfenyloxy group at the α-position of the carbonyl group. This addition−rearrangement can be conducted in a single flask using acid chlorides as starting materials.
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ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b01555.
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Experimental details, characterization data for all new compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected];
[email protected]. ORCID
Chong-Dao Lu: 0000-0001-8968-0134 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (21871292).
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REFERENCES
(1) (a) Coppola, G. M.; Schuster, H. F. α-Hydroxy Acids in Enantioselective Syntheses; Wiley-VCH: Weinheim, 1997. (b) Gu, X.; Wang, L.; Gao, Y.-F.; Ma, W.; Li, Y.-M.; Gong, P. Tetrahedron: Asymmetry 2014, 25, 1573−1580. (2) For early reviews of asymmetric hydroxylation of enolates, see: (a) Davis, F. A.; Chen, B.-C. Chem. Rev. 1992, 92, 919−934. (b) Chen, B.-C.; Zhou, P.; Davis, F. A.; Ciganek, E. In Organic Reactions; Overman, L. E., Ed.; John Wiley & Sons Inc.: New York, 2003; Vol. 62, pp 1−356. (3) For recent examples, see: (a) Maji, B.; Yamamoto, H. Angew. Chem., Int. Ed. 2014, 53, 14472−14775. (b) Wang, D.; Xu, C.; Zhang, L.; Luo, S. Org. Lett. 2015, 17, 576−579. (c) Yang, F.; Zhao, J.; Tang, X.; Zhou, G.; Song, W.; Meng, Q. Org. Lett. 2017, 19, 448−451. (d) Feng, Y.; Huang, R.; Hu, L.; Xiong, Y.; Coeffard, V. Synthesis 2016, 48, 2637−2644. (e) Kanemitsu, T.; Sato, M.; Yoshida, M.; Ozasa, E.; Miyazaki, M.; Odanaka, Y.; Nagata, K.; Itoh, T. Org. Lett. 2016, 18, 5484−5487. (f) Ding, W.; Lu, L.-Q.; Zhou, Q.-Q.; Wei, Y.; Chen, J.-R.; Xiao, W.-J. J. Am. Chem. Soc. 2017, 139, 63−66. (g) Yang, F.; Zhao, J.; Tang, X.; Wu, Y.; Yu, Z.; Meng, Q. Adv. Synth. Catal. 2019, 361, 1673−1677. D
DOI: 10.1021/acs.orglett.9b01555 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters (19) Similarly, protonation product 4b was obtained from the reaction of 1j with 2a in high yield (93%) with poor diastereoselectivity (1.3:1 dr) when the reaction was quenched with an aqueous solution of NH4Cl instead of TMSCl. (20) For early studies on 1,4-asymmetric induction for the reaction of ketenes with optically active amines, see: (a) Pracejus, H. Asymmetrische Synthesen mit Ketenen, II. Justus Liebigs Ann. Chem. 1960, 634, 23−29. (b) Pracejus, H.; Tille, A. Chem. Ber. 1963, 96, 854−865. (c) Schultz, A. G.; Kulkarni, Y. S. J. Org. Chem. 1984, 49, 5202−5206. (21) In contrast, 1,4-asymmetric induction has been achieved in the addition of chiral alcohols to ketenes. For related references, see: (a) Larsen, R. D.; Corley, E. G.; Davis, P.; Reider, P. J.; Grabowski, E. J. J. J. Am. Chem. Soc. 1989, 111, 7650−7651. (b) Cannizzaro, C. E.; Strassner, T.; Houk, K. N. J. Am. Chem. Soc. 2001, 123, 2668−2669. For recent success in catalytic asymmetric ketene aminolysis, see: (c) Hodous, B. L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124, 10006− 10007. (22) Staudaher, N. D.; Lovelace, J.; Johnson, M. P.; Louie, J. Org. Synth. 2017, 94, 1−15. (23) Hertenstein, U.; hünig, S.; Reichelt, H.; Schaller, R. Chem. Ber. 1982, 115, 261−287. (24) Evans, D. A.; Andrews, G. C. Acc. Chem. Res. 1974, 7, 147−155. (25) The enantiomeric ratio for acid 7 was determined by chiral HPLC analysis after conversion of 7 to its methyl ester. For a reported method for enantiopurity analysis of 7, see: Yamanaka, M.; Inaba, M.; Gotoh, R.; Ueki, Y.; Matsui, K. Chem. Commun. 2017, 53, 7513− 7516. (26) The optical rotation for 7 was [α]D24 = −32.5 (c = 0.20, EtOH). The literature indicated [α]D24 = −32.3 (c 1.77, EtOH) for (R)-α-ethyl phenylacetic acid with 97% ee. See: Basavaiah, D.; Krishna, P. R. Tetrahedron 1995, 51, 12169−12178. (27) The presence of a bulky substituent such as Me3SiO at the C2 position in the allylic system of the precursor used for aza-Mislow− Evans rearrangement destabilizes the endo transition state, facilitating exo rearrangement. See: (a) Hoffmann, R. W.; Goldmann, S.; Gerlach, R.; Maak, N. Chem. Ber. 1980, 113, 845−855. (b) Goldmann, S.; Hoffmann, R. W.; Maak, N.; Geueke, K.-J. Chem. Ber. 1980, 113, 831−844.
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