tion reactions of amino R-diazoketones catalyzed by metals
have been used to prepare nitrogen heterocycles,5,6 such as
â-lactams,7 pyrrolidinones,8,9 piperidinones,8,9 and pipecolic
acid.10 The requisite R-diazo compound (SS,R)-(+)-5 was
readily prepared in 91% yield by diazo transfer from
commercially available (4-carboxybenzene)sulfonyl azide (p-
CBSA) and triethylamine (Scheme 2). Since metal carbenoid
Scheme 3
Scheme 2
insertion into the N-H bond of a sulfinamide has not been
reported, the corresponding N-tosyl derivative (R)-(+)-7 was
prepared via two different methods.11 First the diazo sulfi-
namide 5 was oxidized to 7 in 98% yield using m-
chloroperbenzoic acid (m-CPBA). Alternatively this material
was prepared by diazo transfer from N-tosyl δ-amino
â-ketoester 6 (Scheme 2). The diazo compounds are stable
and readily purified by flash chromatography.
Diazo compounds (+)-5 or (+)-7 were treated in DCM
or benzene with 3 mol % of Rh2(OAc)4 at room temperature
or reflux for 2 h. Removal of the solvent and chromatography
gave a complex mixture of products that could not be
characterized. Since the majority of intramolecular carbenoid
N-H insertions involve amides,7-10 the N-Boc derivative
(R)-(+)-9 was prepared as outlined in Scheme 3. The sulfinyl
group in (+)-4 was removed with 5.0 equiv of TFA in MeOH
to give the amine salt (not shown). The solution was
concentrated, dissolved in THF, and treated with Boc2O/Et3N
and a catalytic amount of DMAP. The N-Boc-protected
δ-amino â-ketoester (R)-(+)-8 was obtained in 90% yield
for the two steps. Next, diazo transfer using 4-CBSA/Et3N
gave (R)-(+)-9 in nearly quantitative yield. Remarkably, (R)-
(+)-9 can also be prepared from the N-sulfinyl diazo
compound (+)-5 in 90% yield using the one-pot deprotection/
protection protocol (Scheme 3). It is reported that R-keto
diazo compounds are unstable in the presence of strong acids
such as TFA.9
With 3 mol % of Rh2(OAc)4, (R)-(+)-9 gave the desired
oxo proline 10 as a single diastereoisomer in near quantitative
crude yield (Scheme 3). In solution this material reverts to
an 85:15 mixture of cis:trans isomers and, on chromato-
graphic purification, a 60:40 isomer mixture 11 (vide infra).
NOE and NOESY experiments to determine the structure
of crude 10 were inconclusive. However, reduction of 10
(85:15 mixture) with NaBH4/MeOH gave a 76:14:10 mixture
of alcohols 12 in 85%. Deprotection, TFA/DCM, and
purification gave the major isomer (2S,3R,5R)-(+)-13 in 73%
yield. NOSEY experiments revealed that 13 had the cis
arrangement of substituents (Scheme 3) and strongly sug-
gested that the rhodium carbenoid species inserts into the
N-H bond of 9 to furnish the cis proline derivative 10.
(5) (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds, Wiley-Interscience: New
York, 1998. (b) Doyle, M. P.; McKervey, M. A. Chem. Commun. 1997,
983. (c) Ye, T.; McKervey, M. A. Chem. ReV. 1994, 94, 1091.
(6) Wang, J.; Hou, Y.; Wu, P. J. Chem. Soc., Perkin Trans. 1 1999,
2277.
(7) Salzmann, T. N.; Ratcliffe, R. W.; Christensen, B. G.; Bouffard, F.
A. J. Am. Chem. Soc. 1980, 102, 6161.
(8) Moyer, M. P.; Feldman, P. L.; Rapoport, H. J. Org. Chem. 1985,
50, 5223.
(9) Yang, H.; Jurkauskas, V.; Mackintosh, N.; Mogren, T.; Stephenson,
C. R. J.; Foster, K.; Brown, W.; Roberts, E. Can. J. Chem. 2000, 78, 800.
(10) Garcia, C. F.; McKervey, M. A.; Ye, T. Chem. Commun. 1996,
1565.
(11) For examples of carbenoid insertion into the N-H bond of a
sulfonamide, see: (a) Benati, L.; Calestani, G.; Nanni, D.; Spagnolo, P. J.
Org. Chem. 1998, 63, 4679. See also ref 215 in ref 5c.
1600
Org. Lett., Vol. 4, No. 9, 2002