Synthesis of 1,3-difunctionalized amine derivatives through selective C-H bond oxidation

Full text of DOI:10.1021/ja011033x

J. Am. Chem. Soc. 2001, 123, 6935-6936
Table 1. Oxidative Cyclization of Sulfamate Estersa
6935
Synthesis of 1,3-Difunctionalized Amine Derivatives
through Selective C-H Bond Oxidation
Christine G. Espino, Paul M. Wehn, Jessica Chow, and
J. Du Bois*
Department of Chemistry, Stanford UniVersity
Stanford, California 94305
ReceiVed April 24, 2001
Amination reactions of saturated C-H bonds hold great
potential as methods for the synthesis of amines and amine
derivatives.1,2 We have recently delineated one such process that
makes possible the conversion of 1° carbamates to oxazolidin-
2-ones using dinuclear Rh carboxylate catalysis.2 Further explora-
tions of this chemistry have guided us to sulfamate esters 1 (Figure
1). This uniquely reactive class of compounds affords six-
membered ring insertion products 2 through exclusive γ-C-H
bond amination.3 Such findings contrast distinctly the reactions
of carbamates and serve to define a new, exceptionally versatile
strategy for the preparation of 1,3-amino alcohols and related
â-amino acids.4 Additionally, we have demonstrated that these
seldom described oxathiazinane heterocycles 2 can be converted
following N-carbamoylation into reactive alkylating agents.
Nucleophilic displacement reactions of these electrophiles afford
1,3-difunctionalized compounds with marked efficiency. The
chemistry described herein thus offers powerful methodology for
the construction of myriad amine-derived materials through
selective, intramolecular C-H oxidation.
Figure 1. Rh-catalyzed oxidative cyclization of sulfamate esters.
a (a) Catalyst: A ) Rh2(OAc)4, B ) Rh2(oct)4. (b) Reactions
conducted for ∼2 h with 2 mol % catalyst, 1.1 equiv PhI(OAc)2, and
2.3 equiv MgO in CH2Cl2 at 40 °C; in two cases (entries 5 and 8), 5
mol % catalyst loading was employed. (c) Exclusive product as
determined by 1H NMR of the unpurified reaction mixture. (d)
Reported protocols for the synthesis of sulfamate esters
typically employ sulfamoyl chloride, ClSO2NH2, a convenient
reagent for preparative scale use made easily from inexpensive
ClSO2NCO and formic acid.5 Condensation of ClSO2NH2 with
most 1° and 2° alcohols (pyridine, CH2Cl2) furnishes the target
sulfamates in 65-75% yield.6 These substrates react rapidly (<2
h) at 40 °C with PhI(OAc)2, MgO, and 2 mol % Rh2(OAc)4 to
afford the corresponding six-membered ring insertion products
1
Exclusive product as determined by H NMR of unpurified reaction
mixture; stereochemistry established by nOe experiments. (e) 13:1 syn/
1
1
1
anti by H NMR. (f) 4:1 syn/anti by H NMR. (g) 8:1 cis/trans by H
NMR. (h) Product isolated by crystallization; conversion is >97% from
1H NMR of the unpurified reaction mixture.
(1) For leading references, see: (a) Mu¨ller, P. In AdVances in Catalytic
Processes; Doyle, M. P., Ed.; JAI Press Inc.: Greenwich, 1997; Vol. 2, pp
113-151. (b) Johannsen, M.; Jørgensen, K. A. Chem. ReV. 1998, 98, 1689-
1708. (c) Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J.
Am. Chem. Soc. 1999, 121, 9120-9132. (d) Au, S.-M.; Huang, J.-S.; Che,
C.-M.; Yu, W.-Y. J. Org. Chem. 2000, 65, 7858-7864.
(2) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598-600.
(3) Compound 2 is named as a 1,2,3-oxathiazinane 2,2-dioxide or as a 2,2-
dioxo-tetrahydro-1,2,3-oxathiazine. We refer to such structures as oxathiazi-
nanes for convenience. For a leading reference on the little known chemistry
of these compounds, see: Riddell, F. G.; Royles, B. J. L. In ComprehensiVe
Heterocyclic Chemistry II; Boulton, A. J., Ed.; Pergamon Press: Oxford, 1996;
Vol. 6, pp 825-859.
(4) For recent advances in â-amino acid synthesis, see: (a) EnantioselectiVe
Synthesis of â-Amino Acids; Juaristi, E., Ed.; Wiley-VCH: New York, 1997.
(b) Cole, D. C. Tetrahedron 1994, 50, 9517-9582. (c) Evans, D. A.; Wu, L.
D.; Wiener, J. J. M.; Johnson, J. S.; Ripin, D. H. B.; Tedrow, J. S. J. Org.
Chem. 1999, 64, 6411-6417. (d) Myers, J. K.; Jacobsen, E. N. J. Am. Chem.
Soc. 1999, 121, 8959-8960. (e) Horstmann, T. E.; Guerin, D. J.; Miller, S.
J. Angew. Chem., Int. Ed. 2000, 39, 3635-3638.
through selective γ-C-H insertion (Table 1).7,8 The strong bias
for oxathiazinane formation is presumably accounted for by the
elongated S-O and S-N bonds (1.58 Å) and the obtuse N-S-O
angle (103°) of the sulfamate, which match closely the metrical
parameters of the heterocycle.9 Nonetheless, it is possible to
generate efficiently the five-membered sulfamidate in systems for
which no alternative cyclization pathway is available (entry 9).
C-H amination under Rh-catalysis has general applicability
with a range of structurally disparate starting materials. High
product yields are obtained for sulfamates possessing 3° and
benzylic C-H centers nearly without exception. Although
3° C-H bonds react in preference to 2° -CH2 units (entry 1),
amination of unactivated -CH2 groups is catalyzed effectively.
1
(7) As determined by H NMR of the unpurified reaction mixture.
(5) (a) Benson, G. A.; Spillane, W. J. The Chemistry of Sulfamic Acids,
Esters, and their DeriVatiVes; Patai, S., Rappoport, Z., Eds.; Wiley & Sons:
Chichester, 1991; pp 947-1036. (b) Timberlake, J. W.; Ray, W. J., Jr.; Stevens,
E. D.; Klein, C. L. J. Org. Chem. 1989, 54, 5824-5826.
(6) For an alternative procedure using ClSO2NH2, see: Okada, M.; Iwashita,
S.; Koizumi, N. Tetrahedron Lett. 2000, 41, 7047-7051.
(8) Rh2(OAc)4 and Rh2(oct)4 can be employed interchangeably with no
apparent difference to the reaction outcome.
(9) An X-ray structure of the product from entry 4 has S-O and S-N
bond lengths of 1.59 Å and an N-S-O angle of 105°. Conversely, the
N-S-O angle in sulfamidates is 95°, see: Gritsonie, P.; Pilkington, M.;
Wallis, J. D.; Povey, D. C. Acta Crystallogr. 1994, C50, 763-765.
10.1021/ja011033x CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/22/2001

6936 J. Am. Chem. Soc., Vol. 123, No. 28, 2001
Communications to the Editor
Scheme 1a
a (a) ClSO2NH2, C5H5N, CH2Cl2, 70%; (b) 2 mol % Rh2(OAc)4,
PhI(OAc)2, MgO, CH2Cl2, 91%; (c) CBzCl, NaOtBu, 75%; (d) aq CH3CN,
then cat. TEMPO, NaOCl, NaClO2, 81%.
Figure 2. Representative oxathiazinane ring-opening reactions.
Notably, good to excellent levels of 1,3-diastereoselective induc-
tion are recorded for substrates derived from 2° alcohols having
prochiral -CH2 centers (entries 2, 4, 5, 7).10 Preference for the
1,3-syn isomer ranges from 4 to >20:1, as evidenced in entries
2, 4, and 5, and is consistent with the cyclization event proceeding
through a chairlike transition state.11 1,3-Asymmetric induction
in systems such as these can be exploited for the purpose of
establishing stereogenic amine centers from remote alcohol
groups. Importantly, reactions with chiral substrate probes (entry
3) confirm that sulfamate insertion is stereospecific.2,12 Thus, C-H
amination is suited ideally for the enantiospecific preparation of
quaternary stereocenters given the challenges associated with the
asymmetric synthesis of such functional units.13
of a single-step method for the conversion of 3 to the corre-
sponding N-CBz-â-amino acid 8 (eq 1).4c Addition of H2O to 3
followed by treatment of the resulting alcohol 7 with catalytic
TEMPO, NaOCl, and NaClO2 (phosphate buffer, pH ≈ 3-4)
produces the target compound, N-CBz-â-phenylalanine 8, in 80%
yield without recourse to intermediate purification steps.18 By
conjoining sulfamate ester cyclization with this oxathiazinane ring
opening-oxidation protocol, we have further advanced a concise,
asymmetric synthesis of (R)-N-CBz-â-isoleucine 13 (Scheme 1).19
Synthesis of 13 (1.8 g) is thus accomplished in four straightfor-
ward and readily scalable steps from (S)-3-methyl-1-pentanol 9.20
The multigram preparation of 13 illustrates the salient potential
of our C-H insertion reaction for the efficient assembly of chiral
â-amino acids and optically pure quaternary centers.21
Intramolecular C-H amination using commercial Rh-catalysts,
PhI(OAc)2, and MgO offers a practical solution for the controlled
oxidation of saturated C-H bonds. Reactions of sulfamates with
2 mol % Rh2(OAc)4, PhI(OAc)2, and MgO yield selectively six-
membered ring oxathiazinanes. These novel heterocycles are
shown to have exceptional value as precursors for 1,3-amino
alcohols, â-amino acids, and numerous other 1,3-difunctionalized
amine derivatives. In addition, asymmetric quaternary centers are
constructed with absolute stereocontrol. As such, these new
chemistries should find broad application in synthesis.
The structural homology between oxathiazinanes 2, cyclic
sulfates, and sulfamidates suggested to us that the former
compounds could serve as useful electrophiles.14 To our knowl-
edge, only two prior reports have demonstrated that nucleophilic
ring-opening of these heterocycles is indeed possible. In both
examples, however, vigorous reaction conditions were employed
(e.g., NaCN, DMF, 130 °C).15 We reasoned that carbamoylation
of the -NH moiety might improve the electrophilic reactivity of
2. Accordingly, N-CBz oxathiazinanes 3 and 5 were synthesized
using CBzCl and NaOtBu (80-90%). Ring-opening of these
compounds occurs smoothly with 1° and 2° amines, thiolates,
AcO-, and N3 nucleophiles (Figure 2).16 At slightly elevated
-
Acknowledgment. We are most appreciative to Professors B. M. Trost
and P. A. Wender for their helpful comments. C.G.E. is the recipient of
a NSF Predoctoral Fellowship. J.C. is a Pfizer Summer Undergraduate
Fellowship awardee. J.D.B. gratefully acknowledges the Camille and
Henry Dreyfus Foundation, Johnson Matthey, Merck Research Labora-
tories, Pfizer, and Stanford University for generous gifts and financial
support.
temperatures (45 °C), even weakly reactive species such as water,
1° and 2° alcohols add to 3 and 5.17 The remarkably facile
displacement reactions of N-CBz oxathiazinanes vis-a`-vis 2 raise
considerably the utility of these heterocycles for synthesis.
Supporting Information Available: General experimental protocols
and characterization data for all new compounds including azide and
thiolate ring-opened products not shown in Figure 2 (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA011033X
The effectiveness of the hydrolytic ring-opening of N-CBz
oxathiazinane 3 in aqueous CH3CN has enabled the development
(15) (a) Lyle, T. A.; Magill, C. A.; Pitzenberger, S. M. J. Am. Chem. Soc.
1987, 109, 7890-7891. (b) Meunier, N.; Veith, U.; Ja¨ger, V. Chem. Commun.
1996, 331-332. Our findings show that compounds such as 2 (Figure 1) react
with NaN3 in DMF only at temperatures >110 °C.
(16) CH3CN is employed as solvent with 3 and reactions are typically
conducted at 25 °C. Nucleophilic additions with 5 perform most efficiently
in DMSO at 40 °C.
1
(10) Stereochemical assignment is based on H NMR coupling constants
and an X-ray crystal structure for entry 4. Product ratios are determined by
1H NMR integration of the unpurified reaction mixture.
(11) A similar proposal has been made by Yang to account for the observed
levels of diastereoselectivity in intramolecular oxidation reactions of dioxiranes,
see: Yang, D.; Wong, M.-K.; Wang, X.-C.; Tang, Y.-C. J. Am. Chem. Soc.
1998, 120, 6611-6612.
(17) Alternatively, hydrolysis of the parent oxathiazinane is possible in aq
CH3CN at ∼100 °C (20 h).
(12) Stereospecific C-H insertion has been shown in Rh-catalyzed reactions
of diazoalkanes, see: Taber, D. F.; Petty, E. H.; Raman, K. J. Am. Chem.
Soc. 1985, 107, 196-199. Also, see: Taber, D. F.; Stiriba, S.-E. Chem. Eur.
J. 1998, 4, 990-992 and references therein.
(18) Alcohol oxidation using catalytic TEMPO as described by Merck is
an extremely effective method, see: Zhao, M.; Li, J.; Mano, E.; Song, Z.;
Tschaen, D. M.; Grabowski, E. J. J.; Reider, P. J. J. Org. Chem. 1999, 64,
2564-2566.
(13) For a leading review on the synthesis of 4° stereocenters, see: Corey,
E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388-401.
(14) For recent references on the chemistry of cyclic sulfates and sulfa-
midates, see: (a) Lohray, B. B.; Bhushan, V. AdV. Heterocycl. Chem. 1997,
68, 89-180. (b) Boulton, L. T.; Stock, H. T.; Raphy, J.; Horwell, D. C. J.
Chem. Soc., Perkin Trans. 1 1999, 1421-1429 and references therein. (c)
Byun, H.-S.; He, L.; Bittman, R. Tetrahedron 2000, 56, 7051-7091.
(19) For a racemic preparation of 13, see: Dobrev, A.; Ivanov, C. Monatsh.
Chem. 1968, 99, 1050-1055.
(20) Optically pure 10 is available from TCI or may be prepared
conveniently following a reported protocol, see: Nakamura, Y.; Mori, K. Eur.
J. Org. Chem. 1999, 2175-2182.
(21) (a) Davis, F. A.; Zhou, P.; Chen, B.-C. Chem. Soc. ReV. 1998, 27,
13-18. (b) Abele, S.; Seebach, D. Eur. J. Org. Chem. 2000, 1-15.