Applications of the sulfinimine-mediated asymmetric strecker synthesis to the synthesis of α-alkyl α-amino acids

Article abstract of DOI:10.1021/jo001179z

Addition of Et₂AlCN and i-PrOH to ketosulfinimines (N-sulfinyl imines) affords corresponding α-alkyl α-amino nitriles in moderate to good yields. The diastereoselectivity is largely dependent on the E/Z isomer ratio of the ketosulfinimine. Hydrolysis of the diastereomerically pure amino nitriles affords enantiopure α-alkyl α-amino acids in moderate to good yields.

Full text of DOI:10.1021/jo001179z

8704
J . Org. Chem. 2000, 65, 8704-8708
Ap p lica tion s of th e Su lfin im in e-Med ia ted Asym m etr ic Str eck er
Syn th esis to th e Syn th esis of r-Alk yl r-Am in o Acid s
Franklin A. Davis,* Seung Lee, Huiming Zhang, and Dean L. Fanelli
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122
fdavis@astro.ocis.temple.edu
Received August 3, 2000
Addition of Et2AlCN and i-PrOH to ketosulfinimines (N-sulfinyl imines) affords corresponding
R-alkyl R-amino nitriles in moderate to good yields. The diastereoselectivity is largely dependent
on the E/Z isomer ratio of the ketosulfinimine. Hydrolysis of the diastereomerically pure amino
nitriles affords enantiopure R-alkyl R-amino acids in moderate to good yields.
The high level of interest in R-alkylated R-amino acids1
of the poor de’s and problematic removal of the chiral
auxiliary (Scheme 1).15,16 Vachal and J acobsen recently
described the asymmetric hydrocyanation of prochiral
ketoimines in a process that utilizes a resin-bound chiral
catalyst and which afforded R-amino nitriles with good
to excellent ee’s.17 However, even with these encouraging
results, the diastereoselective Strecker synthesis, which
uses stoichiometric chiral auxiliaries, is still of value
when the ee’s of the catalytic system are modest and/or
cannot be easily upgraded. In this context we report our
studies of the application of the sulfinimine (N-sulfinyl
imine)-mediated asymmetric Strecker synthesis to the
preparation of R-alklylate R-amino acids.
stems from their biological stability,2 their utility in
studies of enzyme mechanisms,3 and their use as enzyme
inhibitors.4 Furthermore, once incorporated into peptides,
these amino acids influence the conformation of the
protein, thereby altering its properties.5 One method
developed for the enantioselective syntheses of the R-alky-
lated R-amino acids1c is the alkylation of chiral nonra-
cemic enolates derived from â-lactams,6 bis-lactims,7
oxazinones,8 imidazolidinones,9 oxazaborolidinone,10 and
alanine dianions.11 Several other methods, such as the
ring-opening of aziridine carboxylate esters,12 have also
been used to prepare these amino acids.13,14
Application of the asymmetric Strecker synthesis to the
synthesis of R-alklylate R-amino acids has generally
involved the addition of “HCN” to optically active aryl
methyl ketoimines and has had limited success because
The sulfinimine-mediated asymmetric Strecker syn-
thesis involves the addition of ethylaluminum cyanoiso-
propoxide [EtAl(O-i-Pr)CN] to a sulfinimine 2 (Scheme
2).18 The [EtAl(O-i-Pr)CN] reagent is generated in situ
by addition of i-PrOH to diethylaluminum cyanide (Et2-
AlCN). With aldimines 2 (R2 ) H), cyanide addition is
highly diastereoselective (85-95%), and simple crystal-
(1) (a) Barrett, G. C. Amino acids, peptides and proteins; The
Chemical Society: London, 1980; Vol. 13, p 1. (b) Hunt, S. In Chemistry
and Biochemistry of the Amino Acids; Barrett, G. C., Ed.; Chapman
and Hall: London, 1985; p 55. (b) Coppala, G. M.; Schuster, H. F.
Asymmetric Synthesis: Construction of Chiral Molecules using Amino
Acids; Wiley: New York, 1987. (c) Williams, R. M. Organic Chemistry
Series Volume 7: Synthesis of Optically Active R-Amino Acids; Baldwin,
J . E., Magnus, P. D., Eds.; Pergamon Press: Oxford, 1989.
(2) Tomilol, C.; Crisma, M.; Pegoraro, S.; Becker, E. L.; Polinelli,
S.; Boesten, W. H. J .; Schoemaker, H. E.; Meijer, E. M.; Kamphuis, J .;
Freer, R. Peptide Res. 1991, 4, 66.
(3) Walsh, J . J .; Metzler, D. E.; Powell, D.; J acobson, R. A. J . Am.
Chem. Soc. 1980, 102, 7138.
(4) For leading references, see: J ung, M. J . In Chemistry and
Biochemistry of the Amino Acids; Barrett, G. C., Ed.; Chapman and
Hall, London 1985; p 227.
(5) For recent examples, see: (a) Burgess, K.; Ho, K.-K.; Pettitt, B.
M. J . Am. Chem. Soc. 1994, 116, 799. (b) Smith, A. B., III; Keenan, T.
P.; Holcomb, R. C.; Sprengeler, P. A.; Guzman, M. C.; Wood, J . L.;
Carroll, P. J .; Hirschmann, R. J . Am. Chem. Soc. 1992, 114, 10672. (c)
Heimgartner, H. Angew. Chem., Int. Ed. Engl. 1991, 30, 238 and
references therein.
(6) (a) Ojima, I. Acc. Chem. Res. 1995, 28, 383. (b) Colson, P.-J .;
Hegedus, L. S. J . Org. Chem. 1993, 58, 5918.
(7) (a) Schollkopf, U. Tetrahedron 1983, 39, 2085. (b) Schollkopf, U.;
Schroder, J . Liebigs Ann. Chem. 1988, 87.
(12) (a) Davis, F. A.; Liu, H.; Reddy, G. V. Tetrahedron Lett. 1996,
31, 5473. (b) Davis, F. A.; Liang, C.-H.; Liu, H. J . Org. Chem. 1997,
62, 3796.
(13) (a) Ito, Y.; Sawamura, M.; Shirakawa, E.; Hayashizaki, K.;
Hayashi, T. Tetrahedron Lett. 1988, 29, 235. (b) Ito, Y.; Sawamura,
M.; Shirakawa, E.; Hayashizaki, K.; Hayashi, T. Tetrahedron, 1988,
44, 5253. (c) Georg, G. I.; Guan, X.; Kant, J . Tetrahedron Lett. 1988,
29, 403. (d) Hua, D. H.; Lagneau, N.; Wang, H.; Chen, J . Tetrahedron:
Asymmetry 1995, 6, 349. (e) J ung, M. E.; D′Amico, D. C. J . Am. Chem.
Soc. 1995, 117, 7379. (f) Kawabata, T.; Wirth, T.; Yahiro, K.; Suzuki,
H.; Fuji, K. J . Am. Chem. Soc. 1994, 116, 10809. (g) Ferey, V.; Toupet,
L.; Le Gall, T.; Mioskowski, C. Angew. Chem., Int. Ed. Engl. 1996, 35,
430. (h) Charette, A. B.; Mellon C. Tetrahedron 1998, 540, 10525. (i)
Ruble, J . C.; Fu, G. C.; J . Am. Chem. Soc. 1998, 120, 11532. (j) Kuwano,
R.; Ito, Y. J . Am. Chem. Soc. 1999, 121, 3236. (k) Trost, B. M.; Ariza,
X. J . Am. Chem. Soc. 1999, 121, 10727.
(14) For a review on the synthesis of R-alkylated R-amino acids,
see: Wirth, T. Angew. Chem., Int. Ed. Engl. 1996, 35, 430.
(15) For reviews on the asymmetric Strecker synthesis, see: (a)
Williams, R. M. Organic Chemistry Series Volume 7: Synthesis of
Optically Active R-Amino Acids; Baldwin, J . E., Magnus, P. D., Eds.;
Pergamon Press: Oxford, 1989. (b) Duthaler, O. R. Tetrahedron 1994,
50, 1539. (c) Kunz, H. in Stereoselective Synthesis, Helmechen, G.;
Hoffmann, R. W.; Mulzer, J .; Schaumann, E., Eds. Houben-Weyl 1995,
E21b, 1931.
(8) (a) Williams, R. M.; Im, M.-N. J . Am. Chem. Soc. 1991, 113, 9276.
(b) Baldwin, J . E.; Lee, V.; Schofield, C. J . Synlett 1992, 249. (c)
Chinchilla, R.; Galindo, N.; Najera, C. Tetrahedron: Asymmetry 1998,
9, 2769.
(9) (a) Seebach, D.; Burger, H. M.; Schickli, C. P. Liebigs Ann. Chem.
1991, 669. (b) Seebach, D.; Aebi, J . D.; Gander-Coquoz, M.; Naef, R.
Helv. Chim. Acta 1987, 70, 1194. (c) J uaristi, E.; Lopez-Ruiz, H.;
Madrigal, D.; Ramirez-Quiros, Y.; Esalante, J . J . Org. Chem. 1998,
63, 4706.
(16) (a) Weinges, K.; Blackholm, H. Chem. Ber. 1980, 113, 3098. (b)
Subramanian, P. K.; Woodard, R. W. Synth. Commun. 1986, 16, 337.
(c) Moon, S.-H.; Ohfune, Y. J . Am. Chem. Soc. 1994, 116, 7405. (d)
Ohfune, Y.; Moon, S.-H.; Horikawa, M. Pure Appl. Chem. 1996, 68,
645. (e) Volk, F.-J .; Frahm, A. W. Liebigs Ann. 1996, 1893. (e) Ma, D.;
Tian, H.; Zou, G. J . Org. Chem. 1999, 64, 120.
(10) Vedejs, E.; Fields, S. C.; Schrimpf, M. R. J . Am. Chem. Soc.
1993, 115, 11612.
(11) Berkowitz, D. B.; Smith, M. K. J . Org. Chem. 1995, 60, 1233.
(17) Vachal, P.; J acobsen, E. N. Org. Lett. 2000, 2, 867.
(18) Davis, F. A.; Portonovo, P. S.; Reddy, R. E.; Chiu, Y.-H. J . Org.
Chem. 1996, 61, 440.
10.1021/jo001179z CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/17/2000

Synthesis of R-Alkyl R-Amino Acids
J . Org. Chem., Vol. 65, No. 25, 2000 8705
Sch em e 1
methyl cyclohexyl sulfinimines 2h and 2i were isolated
as single E-isomers. Sulfinimines derived from pro-
piophenone, 2-butanone, and 2-hexanone, 2d , 2f, and 2g,
respectively, were isolated as inseparable mixtures of
isomers (Table 1). Generally there is a low barrier to
planar inversion in ketone-derived sulfinimines (14-17
kcal/mol), and if the size difference of R1 versus R2 in the
ketone is not sufficiently large, isomeric mixtures are
obtained.26
Sch em e 2
Ethylaluminum cyanoisopropoxide [EtAl(O-i-Pr)CN]
was prepared by treatment of 1.5 equiv of diethylalumi-
num cyanide with 1.0 equiv of i-PrOH and added to a
-78 °C solution of the sulfinimine 2 (Scheme 1). The
reaction mixture was warmed to room temperature,
stirred for 10-18 h, and quenched at -78 °C by addition
of aqueous NH4Cl solution. The diastereomerically pure
amino nitriles 3 were obtained by flash chromatography
(Table 1).
As observed in earlier studies the configuration of the
sulfinyl group controls cyanide addition: Re-face addition
to (S)-2 gives amino nitrile (SS,S)-3 as the major diaste-
reoisomer as was confirmed by conversion to the corre-
sponding amino acids (see below). For sulfinimines
derived from methyl aryl 2a -c, 2e, or methyl alkyl
ketones 2h , 2i that have exclusively the E-geometry, the
de’s ranged from 60 to 98% (Table 1). No particular
pattern was observed for aryl groups having an electron-
withdrawing or -donating group (Table 1: compare
entries 1 and 5). To eliminate the possibility that the
amino nitriles 3 are equilibrating under the reaction
conditions diastereomerically pure (+)-3b was treated
with [EtAl(O-i-Pr)CN] for 10 h. The fact that 3b was
isolated in 97% yield with >98% de strongly suggests that
cyanide addition to the C-N double bond in sulfinimines
is kinetically controlled.
The diastereoselective addition of “CN” to sulfinimines
2d , 2f, and 2g, which exist as mixtures of E:Z isomers,
was low and ranged from 12 to 50% (Table 1: entries 4,
6, and 7). This is because “CN” addition to each of the
isomers is expected to give the corresponding amino
nitrile with opposite stereochemistry. The de’s of 50% for
2f (derived from 2-butanone) and 2g (derived from
2-hexanone) are in line with the 4:1 and 3:1 isomer ratios,
respectively, for the sulfinimines. The lowest de, 12%,
was observed for 2d (derived from propiophenone) which
is undergoing slow E/Z isomerization at room tempera-
ture as indicated by the broad and unresolved protons
of the ethyl group (sulfinimine 2d , Table 1). At -20 °C,
1H NMR indicates 2d exists as a single E isomer.
However, when the temperature of “CN” addition to 2d
was held at -30 to -20 °C for 14 h and quenched at this
temperature, there was no improvement in the de.
To determine the effect of a bulkier sulfinyl group on
the diastereoselectivity, [EtAl(O-i-Pr)CN] was added to
tert-butanesulfinyl ketimines (R)-(-)-5a 27 and (R)-(-)-5b
(Scheme 3). Sulfinimine (R)-(-)-5a , which exists as a
lization or chromatography affords the diastereomerically
pure R-amino nitriles 3. Acid-catalyzed hydrolysis of the
diastereomerically pure 3 not only removes the sulfinyl
auxiliary, but also hydrolyzes the nitrile, which furnishes
the enantiomerically pure (>95%) R-amino acids 4. This
methodology has been used in efficient asymmetric
syntheses of â-fluoro-19 and â-hydroxy R-amino acids,20
(2R,3S)-alloisoleucine,21 the bis(R-amino acids) (2S,6S)-
and meso-(2R,6S)-diaminopimelic acid,22 and (R)-(4-
methoxy-3,5-dihydroxyphenyl)glycine, the central amino
acid of vancomycin.23 Importantly, racemization, even of
sensitive aryl glycines, was not detected.
Ketosulfinimines (SS)-2 were prepared, as previously
described, by condensing commercially available (S)-(+)-
p-toluenesulfinamide (1) with the appropriate ketones in
the presence of 5 equiv of Ti(OEt)4 for 18 h (Scheme 2).24,25
Yields were moderate to good (Table 1). The methyl aryl
sulfinimines 2a -c, 2e, and the methyl tert-butyl and
(19) Davis, F. A.; Srirajan, V.; Titus, D. D. J . Org. Chem. 1999, 64,
6931.
(20) Davis, F. A.; Srirajan, V.; Fanelli, D. L.; Portonovo, P. J . Org.
Chem., in press.
(21) Portonovo, P.; Liang, B.; J oullie, M. M. Tetrahedron: Asymmetry
1999, 10, 1451.
(22) Davis, F. A.; Srirajan, V. J . Org. Chem. 2000, 65, 3248.
(23) Davis, F. A.; Fanelli, D. L. J . Org. Chem. 1998, 63, 1981.
(24) (a) Davis, F. A.; Zhang, Y. Andemichael, Y.; Fang, T.; Fanelli,
D. L.; Zhang, H. J . Org. Chem. 1999, 64, 1403. (b) Fanelli, D. L.;
Szewczyk, J . M.; Zhang, Y.; Reddy, G. V.; Burns, D. M.; Davis, F. A.
Org. Synth. 1999, 77, 50.
(25) Reviews on the chemistry of sulfinimines, see: (a) Zhou, P.;
Chen, B.-C.; Davis, F. A. Syntheses and Reactions of Sulfinimines. In
Advances in Sulfur Chemistry; Rayner, C. M., Ed.; J AL Press:
Stamford, CT, 2000; Vol. 2, pp 249-282. (b) Hua, D. H.; Chen, Y.;
Millward, G. S. Sulfur Rep. 1999, 21, 211. (c) Davis, F. A.; Zhou, P.;
Chen, B.-C. Chem. Soc. Rev. 1998, 27, 13.
(26) (a) Davis, F. A.; Friedman, A. J .; Kluger, E. W. J . Am. Chem.
Soc. 1974, 96, 5000. (b) Davis, F. A.; Kluger, E. W. J . Am. Chem. Soc.
1976, 98, 302.
(27) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J . A.
J . Org. Chem. 1999, 64, 1278.

8706 J . Org. Chem., Vol. 65, No. 25, 2000
Ta ble 1. Ad d ition of Et2AlCN/i-P r OH to Su lfin im in es (S)-2 a n d (R)-5
Davis et al.
products
sulfinimine 2 and 5
amino nitriles 3 and 6
(SS,S):(SS,R) (% de)a
% yield of major
diastereisomer
R-amino acid (S)-4
% isolated yield
entry
R1
R2
(E:Z)
1
2
3
(S)-2a (p-tolyl)
2b
2c
2d
Me
Me
Me
Et
p-MeOPh
p-MePh
Ph
(>99:1)
(>99:1)
(>99:1)
b
9:1 (80)
83:17 (64)
4:1 (60)
56:44 (12)
60
60
77
c
54
64
67
4
Ph
5
6
7
8
9
10
11
2e
2f
2g
2h
Me
Me
Me
Me
Me
Me
Me
p-NO2Ph
Et
n-Bu
Me3C
c-C6H11
Ph
(>99:1)
95:5 (90)
3:1 (50)
3:1 (50)
99:1 (98)
85:15 (70)
(RS,R):(RS,S)-6 12:1 (84)
(RS,R):(RS,S)-6 83:17 (64)
93
49
50
95
72
56e
c
53
69
(4:1)
(3:1)
54
(>99:1)
(>99:1)
(>99:1)
(6.5:1)
50d
2i
48
(R)-4c 64
(R)-5a (t-Bu)
(R)-5b
Et
a
b
NMR of the crude mixture. Sulfinimine 2d and 5b undergo slow E/Z isomerization at room temperature. c Could not be separated
by flashchromatography. R-Amino amide (S)-8 was isolated. e Obtained by crystallization.
d
Sch em e 3
Sch em e 4
In summary, the application of the sulfinimine-medi-
ated asymmetric Strecker synthesis, using N-sulfinyl
ketimines, to the enantioselective synthesis of R-alkyl
R-amino acids was demonstrated.
Exp er im en ta l Section
Gen er a l P r oced u r e. Column chromatography was per-
formed on silica gel, Merck grade 60 (230-400 mesh). Analyti-
cal and preparative thin-layer chromatography was performed
on precoated silica gel plates (250 and 1000 µm) purchased
from Analtech Inc. TLC plates were visualized with UV, in
an iodine chamber or with phosphomolybdic acid unless noted
otherwise. THF was freshly distilled under argon from a purple
solution of sodium and benzophenone.
Unless otherwise stated, all reagents were purchased from
commercial sources and used without additional purification.
Sulfinimines (S)-2c,24a (S)-2g,24a and (R)-5a 27 were prepared
according to literature procedures.
single isomer, gave the corresponding amino nitrile 6a
in 84% de (entry 10). A lower de, 64% was observed for
(R)-(-)-5b which is consistent with the 6.5:1 isomer ratio
(entry 11). While the diastereomeric amino nitriles of 3
were usually readily separated by flash chromatography,
it was not possible to separate 6a ,b in a similar manner.
However, crystallization of 6a afforded the major dias-
tereoisomer (RSR)-(-)-6a in 57% yield (entry 10), but
crystallization was not possible for 6b which exists as
an oil.
(S)-(+)-N-R-Met h yl-(4-m et h ylb en zylid en e)-p -t olu en e-
su lfin a m id e (2a ). Typ ica l P r oced u r e. In an oven-dried 25
mL single-necked round-bottom flask equipped with a mag-
netic stirring bar and a condenser were placed (S)-(+)-p-
toluenesulfinamide (1)24 (0.16 g, 1.0 mmol) and 4′-methyl-
acetophenone (0.67 g, 5.0 mmol) in CH2Cl2 (10 mL). Titanium-
(IV) ethoxide (2.1 mL, 10 mmol) was added, and the reaction
mixture was refluxed for 18 h and cooled to 0 °C, H2O (10 mL)
was added, and the solution was filtered through Celite. The
phases were separated, and the organic phase was washed
with brine (5 mL), dried (MgSO4), and concentrated. Flash
chromatography (EtOAc:hexane, 20:80) afforded 0.18 g (65%)
Hydrolysis of (SS,S)-3 and (RS,R)-(-)-6 was easily
accomplished by refluxing with 6 N HCl for 15 h.
Extraction with ether, to remove the sulfinic acids, and
isolation by ion exchange chromatography (DOWEX 50)
afforded the corresponding amino acids in moderate to
good yields (Table 1). Because the diastereomeric purity
of the amino nitriles was >95% and shown earlier not to
undergo epimerization under these conditions enantio-
meric purity of the amino acids 4 is also >95%. The
enantiomeric purity was further confirmed by comparison
of optical rotations with literature values and by making
the Mosher amides.
Attempts to hydrolyze the N-sulfinyl tert-butyl amino
nitrile 3h to the amino acid failed. Under the standard
conditions, refluxing with 6 N HCl for 15 h, the sulfinyl
group was efficiently removed to give amino nitrile (S)-
(-)-7 in 90% yield (Scheme 4). On treating 7 with concd
H2SO4 for 96 h, R-amino amide (S)-(-)-8 was obtained
in 50% yield. All other attempted conditions failed to
hydrolyze the amide to the acid. This results is undoubt-
edly due to steric inhibition of hydrolysis by the bulky
tert-butyl group.
of (+)-2: mp 104-105 °C; [R]20 117 (c 1.2, CHCl3); IR (KBr)
D
3033, 1589, 1095 cm-1; H NMR (CDCl3) δ 2.38 (s, 3H), 2.40
1
(s, 3H), 2.72 (s, 3H), 7.20 (d, J ) 8.1 Hz, 2H), 7.32 (d, J ) 8.1
Hz, 2H), 7.72 (d, J ) 8.1 Hz, 2H), 7.80 (d, J ) 7.7 Hz, 2H); 13
C
NMR (CDCl3) δ 20.0, 21.3, 125.1, 127.4, 129.0, 129.7, 135.3,
141.6, 142.4, 143.4, 173.8. Anal. Calcd for C16H17NOS: C,
70.81; H, 6.31; N, 5.16. Found: C, 70.75; H, 6.39; N, 5.12.
(S)-(+)-N-r-Meth yl-(4-m eth oxyben zylid en e)-p-tolu en e-
su lfin a m id e (2a ): yield 53%, flash chromatography (EtOAc:
hexane, 20:80); mp 91.5-92.5 °C; [R]20 145.0 (c 1.0, CHCl3);
D
IR (KBr) 1588, 1094 cm-1
;
1H NMR (CDCl3) δ 2.39 (s, 3H),
2.73 (s, 3H), 3.83 (s, 3H), 6.88 (d, J ) 8.4 Hz, 2H), 7.31 (d, J
) 8.1 Hz, 2H), 7.71 (d, J ) 7.7 Hz, 2H), 7.89 (d, J ) 8.4 Hz,

Synthesis of R-Alkyl R-Amino Acids
J . Org. Chem., Vol. 65, No. 25, 2000 8707
2H); 13C NMR (CDCl3) δ 19.5, 20.9, 54.9, 113.3, 124.7, 129.1,
The solution was cooled to -78 °C, and i-PrOH (0.070 mL, 1.0
mmol) was added. The mixture was brought to room temper-
ature, stirred for 30 min, and cannulated to the solution of
(+)-2b at -78 °C. After the reaction mixture was brought to
room temperature and stirred for 15 h, it was cooled to -78
°C and quenched with sat. NH4Cl solution (5 mL). The
suspension was filtered through Celite, extracted with EtOAc
(3 × 5 mL), washed with brine (5 mL), dried (MgSO4), and
concentrated to give a mixture of the amino nitriles 3b (dr
83:17). Preparative TLC (Et2O:CH2Cl2, 5:95) afforded 0.18 g
129.3, 130.1, 142.2, 143.4, 162.3, 173.0. Anal. Calcd for C16H17
-
NO2S: C, 66.87; H, 5.96; N, 4.87. Found: C, 67.27; H, 5.98;
N, 4.71.
[S-(E/Z)]-(+)-N-r-E t h ylb en zylid en e-p -t olu en esu lfin a -
m id e (2d ): yield 54%, flash chromatography (EtOAc:hexane,
20:80); yellow oil (1:1 mixture of E/Z isomers); [R]20 28.8 (c
D
1
1.0, CHCl3); IR (neat) 3057, 2977, 1591, 1095 cm-1; H NMR
(CDCl3) δ 1.25 (m, 3H), 2.41 (s, 3H), 3.25 (b, 2H), 7.32 (m, 2H),
7.41 (m, 2H), 7.47 (m, 1H), 7.74 (b, 2H), 7.86 (b, 2H); 13C NMR
(CDCl3) δ 13.5, 22.1, 27.0, 32.6, 126.0, 128.5, 130.1, 132.3,
142.5, 144.4, 173.6. Anal. Calcd for C16H17NOS: C, 70.81; H,
6.31; N, 5.16. Found: C, 70.89; H, 6.65; N, 4.89.
(S)-(+)-N-r-Meth yl-(4-n itr oben zyliden e)-p-tolu en esu lfi-
n a m id e (2e): yield 51%; flash chromatography (EtOAc:hex-
ane, 20:80); mp 122-123 °C; [R]20D 72.4 (c 1.0, CHCl3); IR (KBr)
1582, 1517, 1347, 1103 cm-1; 1H NMR (CDCl3) δ 2.42 (s, 3H),
2.84 (s, 3H), 7.35 (d, J ) 8.1 Hz, 2H), 7.73 (d, J ) 8.1 Hz, 2H),
8.02 (d, J ) 8.4 Hz, 2H), 8.25 (d, J ) 8.8 Hz, 2H); 13C NMR
(CDCl3) δ 20.9, 22.1, 124.2, 125.8, 129.1, 130.7, 142.9, 143.3,
144.2, 150.1, 172.0. Anal. Calcd for C15H14N2O3S: C, 59.59;
H, 4.67; N, 9.27. Found: C, 59.29; H, 4.60; N, 9.15.
(60%) of (+)-3b as a gel; [R]20 62.1 (c 1.0 CHCl3); IR (neat)
D
2250, 1192 cm-1; 1H NMR (CDCl3) δ 2.08 (s, 3H), 2.37 (s, 3H),
2.41 (s, 3H), 4.62 (s, 1H), 7.24 (d, J ) 8.1 Hz, 2H), 7.31 (d, J
) 7.7 Hz, 2H), 7.54 (d, J ) 8.4 Hz, 2H), 7.62 (d, J ) 8.4 Hz,
2H); 13C NMR (CDCl3) δ 21.0, 21.3, 29.3, 57.1, 120.9, 125.1,
125.7, 129.7, 135.4, 139.4, 141.8, 141.9. Anal. Calcd for
C
17H18N2OS: C, 68.42; H, 6.08; N, 9.39. Found: C, 68.81; H,
6.0.9; N, 9.55.
(2S)-(+)-[(S)-N-(p-Tolu en esu lfin yl]-2-a m in o-2-(4-m eth -
oxyp h en yl)p r op ion itr ile (3a ): dr 9:1; preparative TLC
(Et2O:CH2Cl2, 5:95), yield 60%, gel; [R]20 46.7 (c 1.0 CHCl3);
D
IR (neat) 3153, 2361, 1254, 1153 cm-1; 1H NMR (CDCl3) δ 2.09
(s, 3H), 2.42 (s, 3H), 3.83 (s, 3H), 4.58 (s, 1H), 6.97 (d, J ) 8.5
Hz, 2H), 7.33 (d, J ) 8.1 Hz, 2H), 7.60 (d, J ) 8.1 Hz, 2H),
7.62 (d, J ) 8.5 Hz, 2H); 13C NMR (CDCl3) δ 21.2, 29.3, 56.3,
56.8, 114.3, 121.0, 125.0, 127.2, 127.4, 130.0, 130.1, 141.7,
160.2. Anal. Calcd for C17H18N2O2S: C, 64.94; H, 5.77; N, 8.91.
Found: C, 65.04; H, 5.81; N, 8.59.
(S)-(+)-N-(sec-Bu tylid en e)-p-tolu en esu lfin a m id e (2f):
(4:1, inseparable E:Z mixture favoring the E isomer, yield 74%;
flash chromatography (EtOAc: hexane, 15:85), oil: [R]20 7.5
D
(c 2.4, CHCl3); IR (neat) 3221, 2975, 1616, 1456, 1093 cm-1
;
1H NMR (CDCl3) (E isomer) δ 1.08 (t, J ) 7.5 Hz, 3H), 2.32 (s,
3H), 2.33 (m, 2H), 2.38 (s, 3H), 7.30 (d, J ) 8.0 Hz, 2H), 7.64
(d, J ) 8.0 Hz, 2H); (Z isomer) δ 1.19 (t, J ) 7.2 Hz, 3H), 2.30
(s, 3H), 2.33 (m, 2H), 2.38 (s, 3H), 7.30 (d, J ) 8.0 Hz, 2H),
7.64 (d, J ) 8.0 Hz, 2H); 13C NMR (CDCl3) (E isomer) δ 9.8,
21.8, 22.2, 36.9, 125.6, 130.7, 142.1, 144.1, 183.8; (Z isomer) δ
11.8, 21.8, 27.5, 31.3, 125.7, 130.6, 141.9, 144.1, 185.1. Anal.
Calcd for C11H15NOS: C, 63.12; H, 7.22; N, 6.69. Found: C,
63.01; H, 7.11; N, 6.55.
(2S)-(+)-[(S)-N-p -Tolu en esu lfin yl]-2-a m in o-2-p h en yl-
p r op ion itr ile (3c): dr 4:1; flash chromatography (Et2O:CH2-
Cl2, 5:95), yield 77%, oil; [R]20 69.3 (c 0.5, CHCl3); IR (neat),
D
2230 cm-1; H NMR (CDCl3) δ 2.11 (s, 3H), 2.41 (s, 3H), 4.69
1
(s, 1H), 7.34 (d, 2H, J ) 7.7 Hz), 7.44 (m, 3H), 7.65 (m, 4H);
13C NMR (CDCl3) δ 29.9, 22.1, 57.9, 121.5, 125.7, 126.4, 129.9,
130.2, 130.6, 139.1, 142.4, 142.8. Anal. Calcd for C16H16N2OS:
C, 67.58; H, 5.67; N, 9.85. Found: C, 67.55; H, 5.77; N, 9.74.
(2S)-(+)-[(S)-N-p -Tolu en esu lfin yl]-2-a m in o-2-p h en yl-
bu tyr on itir le (3d ): yield 95%; dr 56:44, attempts to separate
the diastereoisomers by chromatography failed. Oil, [R]20D 45.7
(S)-(+)-(1,2,2-tr im eth yl-p r op ylid en e)-p-tolu en esu lfin a -
m id e (2h ): yield 42%, flash chromatography (EtOAc:hexane,
20:80), oil; [R]20D 29.0 (c 1.0 CHCl3); IR (neat) 2969, 1606, 1093
cm-1 1H NMR (CDCl3) δ 1.14 (s, 9H), 2.32 (s, 3H), 2.41 (s,
;
3H), 7.30 (d, J ) 8.1 Hz, 2H), 7.65 (d, J ) 8.1 Hz, 2H); 13C
NMR (CDCl3) δ 18.3, 21.2, 27.2, 42.3, 125.1, 129.5, 141.3, 143.4,
187.8. Anal. Calcd for C13H19NOS: C, 65.78; H, 8.07; N, 5.90.
Found: C, 66.05; H, 7.85; N, 5.67.
(c 1.0 CHCl3); IR (neat), 3149, 2361, 1057 cm-1 1H NMR
;
(CDCl3) (major) δ 0.98 (m, 3H), 2.21-2.38 (m, 2H), 2.41 (s,
3H), 4.62 (s, 1H), 7.31-7.71 (m, 9H), (minor) δ 0.98 (m, 3H),
2.21 (m, 1H), 2.40 (s, 3H), 2.49 (m, 1H), 4.64 (s, 1H), 7.31-
7.71 (m, 9H); 13C NMR (CDCl3) δ 8.7, 21.2, 35.1, 36.1, 62.8,
63.0, 119.7, 119.9, 124.9, 125.0, 126.5, 126.8, 128.9, 129.0,
129.2, 129.3, 129.6, 129.7, 135.9, 136.5, 141.7, 141.8, 142.1.
Anal. Calcd for C17H18N2OS: C, 68.42; H, 6.08; N, 9.39.
Found: C, 68.72; H, 5.99; N, 9.75.
(S)-(+)-N-(1-Cycloh exyl-eth ylid en e)-p-tolu en esu lfin a -
m id e (2i): yield 51%, flash chromatography (EtOAc:hexane,
20:80), oil; [R]20D 15.0 (c 1.0 CHCl3); IR (neat) 2928, 1612, 1096
1
cm-1; H NMR (CDCl3) δ 1.28 (m, 6H), 1.79 (m, 4H), 2.25 (m,
1H), 2.31 (s, 3H), 2.40 (s, 3H), 7.29 (d, J ) 8.1 Hz, 2H), 7.30
(d, J ) 8.1 Hz, 2H); 13C NMR (CDCl3) δ 21.9, 22.0, 26.4, 30.3,
30.4, 51.5, 125.7, 130.3, 142.2, 144.2, 186.7. Anal. Calcd for
(2S)-(+)-[(S)-N-p-Tolu en esu lfin yl]-2-a m in o-2-(4-n itr o-
p h en yl)p r op ion itr ile (3e): dr 95:5; flash chromatography
(EtOAc:hexane ) 1:4), yield 93%, gel; [R]20D 36.7 (c 0.8 CHCl3);
C
14H19NOS: C, 68.40; H, 8.04; N, 5.32. Found: C, 68.21; H,
1
8.13; N, 5.04.
IR (neat) 3118, 2361, 1092 cm-1; H NMR (CDCl3) δ 2.10 (s,
(R)-(-)-N-(sec-Bu t ylid en e)-2-m et h ylp r op a n esu lfin a -
m id e (5b). Typ ica l P r oced u r e. Sulfinimine 5b was prepared
from (R)-tert-butylsulfinamide27 (0.12 g, 1.0 mmol), methyl
ethyl ketone (0.43 mL, 4.8 mmol), and titanium (IV) ethoxide
(3.1 mL, 15 mmol) in CH2Cl2 (5 mL) according to the procedure
reported by Ellman.27 Flash chromatography (EtOAc:hexane,
30:70) afforded 0.12 g (64%) of (-)-5b as an inseparable E:Z
mixture; oil; [R]20D -203.0 (c 1.0 CHCl3); IR (neat) 2973, 1635,
3H), 2.43 (s, 3H), 4.75 (s, 1H), 7.34 (d, J ) 8.1 Hz, 2H), 7.63
(d, J ) 8.1 Hz, 2H), 7.87 (d, J ) 8.4 Hz, 2H), 8.30 (d, J ) 8.8
Hz, 2H); 13C NMR (CDCl3) δ 21.3, 29.6, 57.0, 119.9, 124.2,
125.0, 127.1, 129.8, 140.9, 142.3, 145.3, 148.2. Anal. Calcd for
C
16H15N3O3S: C, 58.34; H, 4.59; N, 12.76. Found: C, 58.54;
H, 4.69; N, 12.96.
(2S)-(+)-[(S)-N-p -Tolu en esu lfin yl]-2-a m in o-2-m et h yl-
bu tyr on itr ile (3f): dr 3:1; preparative TLC (EtOAc:DCM:
1074 cm-1; H NMR (CDCl3) (E isomer) δ 1.11 (t, J ) 7.3 Hz,
hexane, 30:30:40), yield 49%, oil; [R]20 129.0 (c 1.0 CHCl3);
1
D
1
3H), 1.23 (s, 9H), 2.31 (s, 3H), 2.43 (m, 2H); (Z isomer) δ 1.11
IR (KBr) 3211, 2259, 1099 cm-1; H NMR δ 1.16 (t, J ) 7.5
(t, J ) 7.3 Hz, 3H), 1.22 (s, 9H), 2.16 (s, 3H), 2.71 (m, 2H); 13
C
Hz, 3H), 1.76 (s, 3H), 1.95 (m, 1H), 2.09 (m, 1H), 2.42 (s, 3H),
4.39 (s, 1H), 7.31 (d, J ) 8.0 Hz, 2H), 7.58 (d, J ) 8.0 Hz, 2H);
13C NMR δ 9.24, 22.0, 26.1, 35.2, 55.4, 121.6, 125.9, 130.4,
142.3, 142.7. Anal. Calcd for C12H16N2OS: C, 60.98; H, 6.82;
N, 11.85. Found C, 60.87; H, 6.79; N, 11.66.
NMR (CDCl3) (E isomer) δ 10.5, 22.6, 22.7, 37.3, 56.9, 186.6;
(Z isomer) δ 12.3, 22.6, 23.4, 30.9, 56.9, 186.6. LRMS Calcd
for C8H17NOS: (M + H) 176. Found (M + H) 176.
(2S)-(+)-[(S)-N-p -Tolu en esu lfin yl]-2-a m in o-2-p -t olyl-
p r op ion itr ile (3b). Typ ica l P r oced u r e. In an oven-dried 50
mL two-necked round-bottom flask fitted with a rubber septum
and magnetic stirring bar under an argon balloon was placed
a solution of sulfinimine (+)-2b (0.27 g, 1.0 mmol) in THF (15
mL) and cooled to -78 °C. In a separate 25 mL single-necked
round-bottom flask fitted with a magnetic stir bar and a rubber
septum under an argon balloon was added a solution of
diethylaluminum cyanide (1.5 mL, 1.5 mmol) in THF (5 mL).
(2S)-(+)-[(S)-N-p -Tolu en esu lfin yl]-2-a m in o-2-m et h yl-
h exa n en itr ile (3g): dr 3:1; flash chromatography (EtOAc:
hexane, 5:95), yield 50%; mp 79-79.5 °C; [R]20 128 (c 1.0
D
CHCl3); IR (KBr) 3421, 3154, 2238, 1066 cm-1
;
1H NMR
(CDCl3) δ 0.95 (t, J ) 7.3 Hz, 3H), 1.41 (m, 2H), 1.53 (m, 2H),
1.77 (s, 3H), 1.91 (m, 1H), 2.04 (m, 1H), 2.42 (s, 3H), 4.23 (s,
1H), 7.33 (d, J ) 8.1 Hz, 2H), 7.59 (d, J ) 8.1 Hz, 2H); 13C
NMR (CDCl3) δ 13.7, 21.3, 22.3, 26.0, 26.2, 41.0, 54.1, 121.2,

8708 J . Org. Chem., Vol. 65, No. 25, 2000
Davis et al.
125.2, 130.0, 141.7, 141.9. Anal. Calcd for C14H20N2OS: C,
63.60; H, 7.62; N, 10.60. Found: C, 63.98; H, 7.82; N, 10.51.
(2S)-(+)-[(S)-N-p -Tolu en esu lfin yl]-2-a m in o-2,3,3-t r i-
m eth ylbu tyr on itr ile (3h ): dr 99:1; flash chromatography
Calcd for C9H10N2O4‚1/2H2O: C, 49.32; H, 5.06; N, 12.78.
Found: C, 49.64; H, 4.74; N, 12.86.
(S)-(+)-2-Am in o-2-m eth ylbu ta n oic a cid (isova lin e) (4f):
yield 69%; mp>260 °C, [lit.30 mp 300 °C (sub)]; [R]20 10.2 (c
D
0.8, H2O); [lit.30 [R]20D 10.9 (c 1.0, H2O)]; 1H NMR (D2O) δ 0.88
(EtOAc:hexane, 10:90), yield 95%; mp 135-136 °C, [R]20 185
D
(t, J ) 8.5 Hz, 3H) 1.41 (s, 3H), 1.7 (m, 1H), 1.85 (m, 1H); 13
NMR (D2O + CD3OD) δ 181.2, 66.3, 31.9, 22.5, 6.9.
C
(c 1.0 CHCl3); IR (KBr) 3433, 2223, 1053 cm-1
;
1H NMR
(CDCl3) δ 1.11 (s, 9H), 1.85 (s, 3H), 2.43 (s, 3H), 4.27 (s, 1H),
7.33 (d, J ) 8.1 Hz, 2H), 7.59 (d, J ) 8.1 Hz, 2H); 13C NMR
(CDCl3) δ 19.5, 21.2, 24.5, 38.2, 60.0, 120.8, 125.2, 129.7, 141.7,
141.8. Anal. Calcd for C14H20N2OS: C, 63.60; H, 7.62; N, 10.60.
Found: C, 63.89; H, 7.79; N, 10.61.
(S)-(+)-2-Am in o-2-m eth ylh exa n oic a cid (4g): yield 54%,
mp > 260 °C (dec) (HCl salt); [lit.31 mp 304 °C (dec)], [R]20
D
1
10.5 (c 1.0 H2O), [lit.32 [R]20 8.1 (c 2.0 H2O)]; H NMR (D2O)
D
0.82 (t, J ) 7.6, 3H), 1.13 (m, 2H), 1.28 (m, 2H), 1.41 (s, 3H),
1.67 (m, 1H), 1.81 (m, 1H).
(2S)-(+)-[(S)-N-p-Tolu en esu lfin yl]-2-a m in o-2-cycloh ex-
ylp r op ion itr ile (3i): dr 85:15, prep. TLC (EtOAc:hexane, 30:
(S)-(+)-2-Am in o-2-cycloh exyl-p r op ion ic a cid (4i): yield
48%, mp > 260 °C (dec); [lit.33 mp 326 °C (dec)], [R]20 12.4 (c
70), yield 72%, mp 103-104 °C, [R]20 116 (c 1.0 CHCl3); IR
D
D
1.0 5 N HCl), [lit.33, [R]20 10.85 ( 1.0 (c 1.0 5 N HCl)]; 1H
(KBr) 3158, 2382, 1089 cm-1; 1H NMR (CDCl3) δ 1.21 (m, 6H),
1.73 (s, 3H), 1.86 (m, 4H), 2.01 (m, 1H), 2.42 (s, 3H), 4.24 (s,
1H), 7.32 (d, J ) 8.1, 2H), 7.58 (d, J ) 8.4, 2H); 13C NMR
(CDCl3) δ 21.2, 22.2, 25.8, 26.4, 27.5, 46.7, 57.6, 120.9, 125.2,
129.6, 141.7, 141.8. Anal. Calcd for C15H20N2SO: C, 66.17; H,
7.64; N, 9.65. Found: C, 65.91; H, 7.91; N, 9.70.
D
NMR (D2O) δ 0.98 (m, 2H), 1.13 (m, 2H), 1.25 (m, 2H), 1.47 (s,
3H), 1.64 (m, 2H), 1.76 (m, 2H), 1.82 (m, 1H).
(R)-(-)-2-Meth yl-2-p h en ylglycin e (4c): yield 64%, mp
>260 °C (dec), [lit.29b mp >240 °C (dec)]; [R]20 -85.0 (c 0.7 1
D
N HCl), [lit.30 [R]20 -86.9 (c 0.33 1 N HCl)]; 1H NMR (D2O) δ
D
1.91 (s, 3H), 7.49 (m, 5H).
(2R)-(-)-[(R)-N-ter t-Bu ta n esu lfin yl]-2-a m in o-2-p h en yl-
p r op ion itr ile (6a ): dr 12:1, crystallization (EtOAc:hexane,
(S)-(-)-2-Am in o-2,3,3-tr im eth yl-bu tyr on itr ile Hyd r o-
ch lor id e Sa lt (7). In a 25 mL single-necked round-bottom
flask equipped with a magnetic stir bar were placed 3h (0.26
g, 1.0 mmol) and 6 N HCl (15 mL). After the reaction mixture
was refluxed for 15 h, it was extracted with ether (4 × 10 mL).
The aqueous phase was concentrated to afford 0.15 g (90%) of
25:75) gave 0.16 g (56%) of (-)-6a , mp 88-89 °C; [R]20 -22.4
D
(c 0.8 CHCl3); IR (KBr) 3150, 2363, 1050 cm-1
;
1H NMR
(CDCl3) δ 1.25 (s, 9H), 1.96 (s, 3H), 3.88 (s, 1H), 7.42 (m, 3H),
7.61 (m, 2H); 13C NMR (CDCl3) δ 22.4, 29.7, 56.9, 57.1, 120.6,
125.6, 129.2, 129.4, 139.0. Anal. Calcd for C13H18N2OS: C,
62.37; H, 7.25; N, 11.19. Found: 62.55; H, 7.41; N, 10.96.
(2R)-(-)-[(R)-N-ter t-Bu ta n esu lfin yl]-2-a m in o-2-m eth yl-
bu tyr on itr ile (6b): yield 93%, dr 4.5:1, attempts to separate
(-)-7; mp 165-166 °C, [R]20 -9.0 (c 0.7 H2O); IR (KBr) 3426,
D
2338 cm-1; 1H NMR (D2O) δ 1.11 (s, 9H), 1.66 (s, 3H); 13C NMR
(CDOD3) δ 20.6, 25.1, 38.0, 60.2, 118.7. Anal. Calcd for C7H15
-
the diastereoisomers by chromatography failed; oil; [R]20
ClN2: C, 51.69; H, 9.29; N, 17.22. Found: C, 51.77; H, 9.65; N
16.89.
D
-69.2 (c 0.5 CHCl3); IR (neat) 3432, 2350, 1052 cm-1; 1H NMR
(CDCl3) (major) δ 1.12 (m, 3H), 1.27 (s, 9H), 1.62 (s, 3H), 1.89-
2.08 (m, 2H), 3.44 (s, 1H), (minor) δ 1.12 (m, 3H), 1.25 (s, 9H),
1.78 (s, 3H), 1.89-2.08 (m, 2H), 3.34 (s, 1H); 13C NMR (CDCl3)
δ 9.2, 9.4, 23.0, 26.3, 27.3, 35.1, 35.3, 55.3, 56.4, 57.3, 57.4,
121.4, 121.8. Anal. Calcd for C9H18N2OS: C, 53.43; H, 8.97;
N, 13.85. Found: C, 53.03; H, 9.20; N, 13.67.
(S)-(-)-2-Am in o-2,3,3-tr im eth yl-bu tyr a m id e (8). In a 25
mL single-necked round-bottom flask equipped with a mag-
netic stirring bar was placed concd H2SO4 (10 mL), it was
cooled to 0 °C, and 7 (0.10 g, 0.61 mmol) was added slowly.34
The reaction mixture was stirred at 0 °C for 3 h and at room
temperature for 96 h. The solution was poured onto crushed
ice (25 g) and filtered. The filtrate was slowly adjusted to pH
8 with concentrated NH4OH at 0 °C and extracted with ether
(5 × 10 mL). The combined organic phases were washed with
brine (5 mL), dried (MgSO4), and concentrated to afford 0.044
(S)-(+)-2-Meth yl-(2-(p-tolyl)glycin e (4b). Typ ica l P r o-
ced u r e. In a 25 mL single necked round-bottom flask fitted
with a magnetic stirring bar and condenser was placed (+)-
3b (0.20 g, 0.67 mmol) in 6 N HCl (15 mL). After the solution
was refluxed for 15 h, it was cooled to room temperature and
extracted with ether (3 × 15 mL). The aqueous layer was
passed through 6-8 g of DOWEX 50 ion exchange column
eluting with 1.4 N NH4OH (30 mL). Concentration afforded
g (50%) of (-)-8; mp 162-3 °C, [R]20 -68.0 (c 0.2 CHCl3); IR
D
(KBr) 3510, 1721 cm-1; H NMR (CDCl3) δ 1.03 (s, 9H), 1.31
1
(s, 3H), 5.58 (b, 2H), 7.36 (b, 2H); 13C NMR (CD3OD) δ 23.2,
25.7, 37.2, 62.1, 179.8. Anal. Calcd for C7H16N2O: C, 58.30;
H, 11.18; N, 19.42. Found: C, 58.44; H, 11.20; N, 19.79.
Gen er al P r ocedu r e for P r epar ation of Mosh er Am ides.
Under an argon balloon, in an oven-dried 5 mL two-necked
0.078 g (64%) of 4b, mp 245 (dec) °C; [R]20 63.7 (c 0.7 1, N
D
HCl); IR (KBr) 3156 (b), 1698 cm-1; H NMR (D2O) δ 1.89 (s,
1
3H), 2.34 (s, 3H), 7.31 (d, J ) 8.1 Hz, 2H), 7.38 (d, J ) 8.1 Hz,
2H); 13C NMR (CD3OD) δ 21.0, 22.8, 63.9, 127.0, 130.3, 137.7,
139.5, 175.7; HRMS Calcd for C10H13NO2 (M + H) 180.1025;
found (M + H) 180.1021.
round-bottom flask fitted with
a magnetic stir bar and
condenser, were placed the appropriate amino acid 4 (0.10
mmol), Mosher’s chloride (0.025 g, 0.10 mmol), and propylene
oxide (30 µL, 0.51 mmol) in THF (2 mL). The suspension was
refluxed for 3 h, cooled to room temperature, and concentrated.
Preparative TLC (EtOAc:hexane, 25:75) afforded the Mosher
amide of 4. 19F and 1H NMR was used to evaluate the
enantiomeric purity of the acids.
(S)-(+)-2-Meth yl-2-(4-m eth oxyp h en yl)glycin e, h yd r o-
ch lor id e sa lt (4a ): yield 54%, mp > 260 °C, [lit.,28 mp > 260
°C]; [R]20 74.0 (c 0.66, 1 N HCl), [lit.28 [R]20 70.4 (c 1.0 1 N
D
D
HCl)]; 1H NMR (D2O) δ 1.89 (s, 3H), 3.84 (s, 3H), 7.05 (d, J )
8.4 Hz, 2H), 7.45 (d, J ) 8.4 Hz, 2H).
(S)-(+)-2-Meth yl-2-p h en ylglycin e (4c): yield 67%; mp 294
°C [lit.29b mp >294]; [R]20 79.2 (c 0.5, 1 N HCl), [lit.29b [R]20
Ack n ow led gm en t. This work was supported by the
National Institutes of Health (GM57870).
D
D
86.5 (c 0.52, 1 N HCl)]. Spectral properties were in agreement
with literature values.29a
Su p p or tin g In for m a tion Ava ila ble: IR, 1H NMR, and
13C NMR spectra for sulfinimine 5b. This material is available
free of charge via the Internet at http://pubs.acs.org.
(S)-(+)-2-Meth yl-2-(4-n itr oph en yl)glycin e (4e): yield 53%;
mp 152-153 °C; [R]20 72.1 (c 0.6 1 N HCl); IR (KBr) 3613-
D
2363, 1521, 1513, 1361 cm-1; H NMR (D2O) δ 1.96 (s, 3H),
1
7.74 (d, J ) 8.4 Hz, 2H), 8.31 (d, J ) 8.4 Hz, 2H); 13C NMR
(CDOD3) δ 22.4, 63.2, 123.9, 127.8, 146.9, 148.4, 173.4. Anal.
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