Intermolecular alkyl radical additions to enantiopure N-tert-butanesulfinyl aldimines

Article abstract of DOI:10.1021/ol400439g

The sulfinyl group in (R)-N-tert-butanesulfinyl aldimines provides efficient control of the stereoselectivity in the intermolecular reactions with alkyl radicals. The methodology is applicable to aryl, heteroaryl, benzyl, and alkynyl imines, even those containing CN, CO₂Me, COR, and OH groups. The best results are attained with hindered radicals (tertiary and secondary ones) without C=N bond reduction. This reaction complements the well-established organometallic additions to N-sulfinyl aldimines to obtain enantiomerically pure functionalized α-branched primary amines.

Full text of DOI:10.1021/ol400439g

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Intermolecular Alkyl Radical Additions
to Enantiopure N-tert-Butanesulfinyl
Aldimines
ꢀ
ꢀ
ꢀ
Jose A. Fernandez-Salas, M. Carmen Maestro,* M. Mercedes Rodrıguez-Fernandez,*
´
ꢀ
ꢀ
Jose L. Garcıa-Ruano,* and Ines Alonso
´
´
Departamento de Quımica Organica, Facultad de Ciencias, Universidad Autonoma de
Madrid, 28049-Cantoblanco, Madrid, Spain
ꢀ
ꢀ
carmen.maestro@uam.es; mercedes.rodriguez@uam.es; joseluis.garcia.ruano@uam.es
Received February 15, 2013
ABSTRACT
The sulfinyl group in (R)-N-tert-butanesulfinyl aldimines provides efficient control of the stereoselectivity in the intermolecular reactions with alkyl
radicals. The methodology is applicable to aryl, heteroaryl, benzyl, and alkynyl imines, even those containing CN, CO2Me, COR, and OH groups.
The best results are attained with hindered radicals (tertiary and secondary ones) without CdN bond reduction. This reaction complements the
well-established organometallic additions to N-sulfinyl aldimines to obtain enantiomerically pure functionalized R-branched primary amines.
The nucleophilic addition of organometallic reagents to
imine derivatives is one of the most important methods to
prepare a broad range of R-branched amines,1 which are
present in biologically active compounds and are valuable
synthetic building blocks. The main drawbacks limiting
its scope are the aza-enolization,2 the compatibility of the
reagents with electrophilic functional groups, and the
competitive formation of reduction products.3 Moreover,
hindered reagents, such as t-BuMgBr or t-BuLi, usually fail
to give addition products.4 N-Sulfinimines5 have usually
been the substrates of choice to synthesize R-branched
amines mediated by carbon nucleophiles. The use of these
sulfinyl derivatives, especially those carrying the bulky tert-
butyl group, has solved the aza-enolization (it is slower than
the nucleophilic addition), but most of the drawbacks
associated with the nucleophilic addition to imines remain.
Diastereoselective CdN reduction of N-sulfinyl ketimines6
has been less used because of the added problem of the E/Z
equilibration. Then, good results were only obtained for
aryl/n-alkyl (Me, Et, nPr, nBu) N-tert-butanesulfinylke-
timines,6aꢀc whereas they are poorer for aryl/t-Bu (23%,
92% de) and aryl/i-Pr (82%, 70% de) ketimines.6d
The intermolecular radical addition to aldimine
derivatives7 offers some advantages as an alternative
method. It takes place under mild and neutral conditions
(1) Nugent, T. C., Ed. Chiral Amine Synthesis: Developments and
Applications; Wiley-VCH: Chichester, U.K., 2010.
(2) (a) Stork, G.; Dowd, S. R. J. Am. Chem. Soc. 1963, 85, 2178. (b)
Wittig, G.; Frommeld, H. D.; Suchanek, P. Angew. Chem., Int. Ed. Engl.
1963, 2, 683. (c) Guerrier, L.; Royer, J.; Grierson, D. S.; Husson, H.-P.
J. Am. Chem. Soc. 1983, 105, 7754. (d) Enders, D.; Diez, E.; Fernandez,
R.; Martin-Zamora, E.; Munoz, J. M.; Pappalardo, R. R.; Lassaletta,
J. M. J. Org. Chem. 1999, 64, 6329.
(6) (a) For a review, see: Nugent, T. C.; El-Shazly, M. Adv. Synth.
Catal. 2010, 352, 753 and references cited therein. (b) Borg, G.; Cogan,
D. A.; Ellman, J. A. Tetrahedron Lett. 1999, 40, 6709. (c) Guijarro, D.;
Pablo, O.; Yus, M. J. Org. Chem. 2010, 75, 4419 and references cited
therein. (d) Xiao, X.; Wang, H.; Huang, Z.; Yang, J.; Bian, X.; Qin, Y.
Org. Lett. 2006, 8, 1390.
(3) Liu, G.; Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1997, 119,
9913.
(4) Moody, C. J.; Gallagher, P. T.; Lightfoot, A. P.; Slawin, A. M. Z.
J. Org. Chem. 1999, 64, 4419.
(7) Reviews on intermolecular radical addition to CdN bonds:
(a) Rowlands, G. J. Tetrahedron 2009, 65, 8603. (b) Bazin, S.; Feray,
L.; Bertrand, M. Chimia 2006, 60, 260 and references cited therein.
(c) Friestad, G. K.; Mathies, A. K. Tetrahedron 2007, 63, 2541. (d)
Pastori, N.; Gambarotti, C.; Punta, C. Mini-Rev. Org. Chem 2009, 6,
184. (e) Akindele, T.; Yamada, K.; Tomioka, K. Acc. Chem. Res. 2009,
42, 345. (f) Miyabe, H.; Yoshioka, E.; Kohtani, S. Curr. Org. Chem 2010,
14, 1254 and references cited therein.
(5) For reviews, see: (a) Zhou, P.; Chen, B. C.; Davis, F. A. Tetra-
hedron 2004, 60, 8003. (b) Morton, D.; Stockman, R. A. Tetrahedron
2006, 62, 8869. (c) Lin, G.-Q.; Xu, M.-H.; Zhong, Y.-W.; Sun, X.-W.
Acc. Chem. Res. 2008, 41, 831. (d) Ferreira, F.; Botuha, C.; Chemla, F.;
ꢀ
Perez-Luna, A. Chem. Soc. Rev. 2009, 38, 1162. (e) Robak, M. T.;
Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600.
r
10.1021/ol400439g
XXXX American Chemical Society

that avoid the aza-enolization, is tolerated by a wide range
of functional groups, and does not produce CdN bond
reduction. Diastereo-8 and enantioselective9 intermolecu-
lar radical additions to the CdN bond, including radical
reductions,10 have been developed in the past few years
with the most efficient enantioselective process involving
the use of chiral Lewis acids9aꢀc and organocatalysts9dꢀg
on hydrazones or oxime ethers as radical acceptors. The
stoichiometric amounts of the catalyst often required to obtain
high enantioselectivity and the need for additional cleavage
steps, using SmI2 and HMPA, to attain the corresponding
free amines are the main handicap of these reactions.
N-sulfinylimines. This observation prompted us to evalu-
ate the utility of these radical reactions to prepare enantio-
merically pure R-branched amines. The results obtained in
this study are reported herein.
Initially, we examined the isopropyl radical addition to
enantiopure (R)-N-tert-butanesulfinyl imine 3Aasa model
substrate16 to find the optimal reaction conditions (Table 1).
Table 1. Optimization of the Reaction Conditions for Imine (R)-3A
N-Sulfinylimines have been scarcely studied as radical
acceptors in the diastereoselective process (to our knowl-
edge, only their cross-coupling reactions with carbonyl
compounds mediated by SmI2,11 and the radical additions
of ethers and acetals12 mediated by Me2Zn-air, have
been reported). Therefore, the stereoselective CꢀC bond
formation based on the intermolecular carbon-centered
radical addition to these imine derivatives remains as a
challenging and promising task.
The usually accepted model to explain the stereoselec-
tivity of the reactions of N-sulfinylimines with organome-
tallics is based on the association of substrate and reagent
with the metal5e,13 as a previous step to the intramolecular
nucleophilic addition. As the latter is not possible for
radicaladditions, apresumably low stereoselectivitywould
be expected for these reactions, accounting for the lack
of studies about this topic. However, the open transition
states14,15 invoked to explain the highly stereoselective
behavior of organolithium compounds in coordinating
solvents could be applicable to the radical additions to
Lewis
acid
t
yield
(%)a
drb
entry
hydride
(h)
(R/S)
c
1
2
3
4
5
6
7
8
ꢀ
Bu3SnH
Bu3SnH
Bu3SnH
Bu3SnH
Bu3SnH
ꢀ
8
ꢀ
ꢀ
BF3 OEt2
3
(R)-5Aa(91)
(R)-5Aa(91)
>98:2
>98:2
ꢀ
3
d
BF3 OEt2
1.1
6.5
1
3
c
Yb(OTf)3
TMSOTf
ꢀ
e
ꢀ
ꢀ
c
BF3 OEt2
8
ꢀ
ꢀ
3
f
BF3 OEt2
CySiH3
(TMS)3SiH
6
ꢀ
ꢀ
3
TMSOTf
3
(R)-5Aa(60)
>98:2
a Isolated yield. b Determined by 1H NMR of the crude materials.
c Starting material was recovered. d 2.1 equiv of BF3 OEt2 and 10 equiv
3
of i-PrI were used. e Reduction product PhCH2NHSOtBu was observed.
f i-Pr adducts were not observed at the crude mixture.
Et3B/O2 was chosen as a radical initiator system since
it allowed the reaction to start at a low temperature
(ꢀ78 °C).17 The radical addition, mediated by tributyltin
hydride as a chain carrier, failed without Lewis acid
(8) (a) Friestad, G. K.; Baltrusaitis, J.; Korapala, C., S.; Qin, J.
J. Org. Chem. 2012, 77, 3159. (b) Friestad, G. K. Top. Curr. Chem. 2012,
320, 61 and references cited therein. (c) Miyabe, H. Synlett 2012, 23,
activation (entry 1), and only in the presence of BF3 OEt2
3
ꢀ
did it proceed with excellent diastereoselectivity and good
yield (compare entries 2, 4, and 5). As the amount of Lewis
acid increased to 2.1 equiv,18 a shorter reaction time was
observed, though the yield and the diastereoselectivity
remain unaltered (entry 3). All the attempts carried out
to avoid the use of Bu3SnH were not successful (entries 6
and 7). Only the combined treatment with TMSOTf and
(TMS)3SiH afforded the i-Pr adduct in moderate yield and
highdiastereoselectivity (compareentries 2 and 8, Table1).
Then, we choose as the optimal conditions those from
entry 3, which provide a 91% yield and complete control of
the stereoselectivity. This is a remarkable result, in contrast
to the modest yield observed in most of the nucleophilic
additions studied, due to the competence with the reduc-
tion processes.13,19,20
1709. (d) Fernandez, M.; Alonso, R. Org. Lett. 2003, 5, 2461.
(9) (a) Sibi, M. P.; Manyem, S.; Zimmerman, J. Chem. Rev. 2003, 103,
3263. (b) Friestad, G. K.; Shen, Y. H.; Ruggles, E. L. Angew. Chem., Int.
Ed. 2003, 42, 5061. Ketimines as radical acceptors: (c) Miyabe, H.;
Yamaoka, Y.; Takemoto, Y. J. Org. Chem. 2006, 71, 2099. (d) Cho,
D. H.; Jang, D. O. Chem. Commun. 2006, 48, 5045. (e) Jang, D. O.; Kim,
S. Y. J. Am. Chem. Soc. 2008, 130, 16152. (f) Kim, S. Y.; Kim, S. J.; Jang,
D. O. Chem.;Eur. J. 2010, 16, 13046. (g) Lee, S.; Kim, S. Tetrahedron
Lett. 2009, 50, 3345.
(10) Quin, J.; Friestad, G. K Tetrahedron 2003, 59, 6393.
(11) (a) Zhong, Y.-W.; Dong, Y.-Z.; Fang, K.; Izumi, K.; Xu, M.-H.;
Lin, G.-Q. J. Am. Chem. Soc. 2005, 127, 11956. (b) Liu, R.-C.; Wei,
J.-H.; Wei, B.-G.; Lin, G.-Q. Tetrahedron: Asymmetry 2008, 19, 2731. (c)
Liu, R.-C.; Fang, K.; Wang, B.; Xu, M.-H.; Lin, G.-Q. J. Org. Chem.
2008, 73, 3307. (d) Wang, R.; Fang, K.; Sun, B.-F.; Xu, M.-H.; Lin,
G.-Q. Synlett 2009, 2301–2304. (e) Wang, B.; Liu, R.-H. Eur. J. Org.
Chem. 2009, 2845. (f) Wang, B.; Wang, Y. J. Org. Lett. 2009, 11, 3410.
(12) (a) Akindele, T.; Yamamoto, Y.; Maekawa, M.; Umeki, H.;
Yamada, K.; Tomioka, K. Org. Lett. 2006, 8, 5729. (b) Akindele, T.;
Yamada, K.; Sejima, T.; Maekawa, M.; Yamamoto, Y.; Nakano, M.;
Tomioka, K. Chem. Pharm. Bull. 2010, 58, 265.
(13) (a) Davis, F. A.; Reddy, R. T.; Reddy, R. E. J. Org. Chem. 1992,
57, 6387. (b) Cogan, D. A.; Liu, G.; Ellman, J. A. Tetrahedron 1999, 55,
8883.
(14) (a) Plobeck, N.; Powell, D. Tetrahedron: Asymmetry 2002, 13,
303. (b) Pflum, D. A.; Krishnamurthy, D.; Han, Z.; Wald, S. A.;
Senanayake, C. H. Tetrahedron Lett. 2002, 43, 923.
(15) Open transition states have been also suggested to explain the
stereochemical results obtained in Grignard and R2Zn additions to the
N-tert-butanesulfinyl aldimines: (a) Davis, F. A.; Mc.Coull, W. J. Org.
Chem. 1999, 64, 3396. (b) Buesking, A. W.; Baguley, T. D.; Ellman, J. A.
Org. Lett. 2011, 13, 964.
(16) N-p-Toluenesulfinyl benzaldimine, under the same experimental
conditions, provided a lower diastereomeric ratio (88:12).
(17) Miura, K.; Ichinose, Y.; Nozaki, K.; Fugami, K.; Oshima, K.;
Utimoto, K. Bull. Chem. Soc. Jpn. 1989, 62, 143.
(18) BF3 coordination at the O and N atoms of the sulfinyl imine has
been reported: (a) Rode, J. E.; Dobrowolski, J. C. Chirality 2012, 24, 5.
(b) Dobrowolski, J. C.; Kawecki, R. J. Mol. Struct. 2005, 734, 235.
(c) Also see ref 15a.
(19) Jiang, W.; Chen, C.; Marinkovic, D.; Tran, J. A.; Chen, C. W.;
Arellano, L. M.; White, N. S.; Tucci, F. C. J. Org. Chem. 2005, 70, 8924.
B
Org. Lett., Vol. XX, No. XX, XXXX

Then, we investigated the scope of the reaction toward
a wide range of halides as a radical source. The results,
depicted at Table 2, indicate that the stereoselectivity
control is complete in all the studied reactions. The addition
of secondary alkyl radicals give excellent yields (entries 1
and 2). The use of alkylbromides instead of the iodides does
not affect the stereoselectivity, but the yield is poorer.
This is also the case with radicals containing heteroatoms
(entry 3), which require an excess of the Lewis acid
(presumably due to their mutual association).
(S)-5Ag (32%) and (S)-5Ag0 (40%), produced by a radical
substitution at the S atom. The N-desulfinylation of the
above mixture gave the corresponding amine in enantio-
merically pure form (see Supporting Information (SI)),
indicating complete control of the stereoselectivity at the
initial radical addition.
To state the generality and scope of the reaction, a wide
range of (R)-N-tert-butanesulfinyl aldimines were sub-
jected to the above optimized conditions. The results are
summarized in Table 3.
The reaction of benzylidene imine 3A with the tert-butyl
radical (entry 4) produced the addition product (R)-5Ad in
75% yield and complete control of the stereoselectivity.
This is a very interesting result because, to our knowledge,
there are no reports describing the efficient incorporation
of tertiary residues by nucleophilic additions to N-sulfiny-
limines. Other functionalized tertiary residues were also
introduced in a completely stereoselective way (entry 5).
Table 3. Scope of the Isopropyl Radical Addition to Imines 3
t
yield (%)a
drb
Table 2. Alkyl Radical Addition to Imine (R)-3A
entry
imine (R)
3A (Ph)
(h)
1
1.1
0.5
0.7
0.5
4
(R)-5Aa (91)
(R)-5Ba (89)
(R)-5Ca (90)
(R)-5 Da (98)
(R)-5Ea (72)c
(R)-5Fa (80)d,e
(R)-5Ga (70)f
(R)-5Ha (75)
(R)-5Ia (60)
(R)-5Ja (72)g
(R)-5Ka (80)
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
>98:2
95:5
2
3B (p-CNC6H4)
3C (p-BrC6H4)
3D (p-CO2MeC6H4)
3E (p-COMeC6H4)
3F (p-CHOC6H4)
3G (p-OHC6H4)
3H (p-OMeC6H4)
3I (2-furyl)
3
4
5
6
1
7
3
8
2
9
0.7
3
10
11
3J (Bn)
3K (CtCPh)
0.2
>98:2
a Isolated yield. b Determined by 1H NMR of the crude materials.
c The reaction was carried out atꢀ98 °C. d 3.5 equivof Bu3SnH. e See text.
f 2.5 equiv of Et3B/O2 were added each hour. g 1.1 equiv of BF3 OEt2.
3
a Isolated yield. b Determined by 1H NMR of the crude materials.
c Starting from c-hexylbromide, a 50% conversion was attained yielding
a mixture of 4Ab (>96% de) and the reduction product. d 6 equiv of
First, we studied the addition with a large number of
p-substituted aryl and heteroaryl aldimines.23 Regardless
of the electronic character of the substituent, the yields
ranged from good to excellent (entries 2ꢀ9). The compat-
ibility of the reaction conditions with the presence of
groups such as CN, CO2Me,24 CO, and OH was remark-
able, as this would have been affected by most of the
organometallics. The use of Bu3SnH determined the re-
duction of the carbonyl group at 3E and 3F at ꢀ78 °C. The
competitive reaction could be avoided for 3E by a decrease
in the reaction temperature. Thus, complete chemo- and
BF3 OEt2 were used (see SI for experimental details). e 13 equiv of RI
3
f
were used. Compound (S)-5Ag0 was isolated as pure diastereomer
(sulfur configuration not determined).
The reaction of primary radicals mediated by the Et3B/O2
system usually results in complications because of the
presence of ethyl radicals or of a competitive reduction.21
We found no problems starting from ethyl iodide, and the
reaction took place with excellent diastereoselectivity
though moderate yield (entry 6). Interesting results were
obtained in the addition of iodomethyl pivalate22 to 3A
(entry 7). It afforded a mixture of the expected compound
(23) Futher extension of the process to the less reactive N-sulfinyl
ketimine derived from acetophenone was unsuccessful.
(24) It is remarkable that the acid resulting in the hydrolysis of 5Da
has been used for obtaining antidiabetic agents (See:Demong, D.; Miller,
M. W.; Dai, X.; Stamford, A. PCT Int Appl. (2012) WO 2012/009226 A1)
andsubstitutedhydroxamic acids employed asinhibitorsofHDCAC6(histone
deacetylase 6) (See: Blackburn, C.; Gigstad, K. M.; Harrison S. J.; Xu, H. PCT
Int Appl. (2011) WO2011/106632 A1). In these patents, the addition of i-PrLi
to an N-tert-butanesulfinylaldimine is the key step in the synthesis of the
starting acid. It requires starting from a t-Bu ester (to avoid nucleophilic attack
to the carbonyl group) and yields a mixture of diastereoisomers that, once
separated, give a 46% yield of the appropriated one. By contrast, in our case,
we perform the radical addition starting from the methyl ester (3D) with
complete control of the stereoselectivity and quantitative yield (entry 4,
Table 3).
(20) The reduction process was not observed using zincates
(Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron Lett. 2009, 50,
3198), which provided a similar yield (90%) but lower stereoselectivity
(94:6 dr) than those indicated in entry 3 in Table 1 (91%; >98:2 dr).
(21) Friestad, G. K.; Draghici, C.; Soukri, M.; Qin, J. J. Org. Chem.
2005, 70, 6330.
(22) (a) Yamada, K.; Nakano, M.; Maeskawa, M.; Akindele, T.;
Tomioka, K. Org. Lett. 2008, 10, 3805. (b) Yamada, K.; Konishi, T.;
Nakano, M.; Fujii, S.; Cadou, R.; Yamamoto, Y.; Tomioka, K. J. Org.
Chem. 2012, 77, 1547.
Org. Lett., Vol. XX, No. XX, XXXX
C

diastereoselectivity for the radical addition were attained
at ꢀ98 °C (entry 5). Starting from 3F (entry 6), an amino-
alcohol was obtained (as a result of the simultaneous
addition of the isopropyl radical to the CdN bond and
the reduction of the formyl group). The compound was
oxidized with MnO2 to afford 5Fa in an 80% overall yield
and >98% de. Heteroarylimines (3I) and arylimines bear-
ing EDG (3G and 3H) also gave good results (entries 7ꢀ9).
The alkylidene imine 3J successfully afforded the expected
product (entry 10).25 Alkynyl imine 3K (entry 11), with a
potentially competitive triple bond, underwent the radical
addition to the CdN bond with complete chemo- and
diastereoselectivity.
Figure 1. Relative conformational stability around the NꢀS
bond at N-sulfinyl imines. Stereochemical prediction (CPCMTHF
mPW1PW91/6-311G(d,p)//6-31G(d)).
/
Finally, removal of the sulfinyl group with HCl/MeOH
at rt produced amine hydrochlorides 6 in almost quanti-
tative yields, without erosion of the enantiomeric purity
(Scheme 2).29
Scheme 1. One-Pot Synthesis of Sulfinamides (between brackets,
overall yield using the conventional two-step procedure)
Scheme 2. tert-Butanesulfinyl Group Removal30
The synthesis of the N-sulfinylamines 5 can be readily
performed from the aldehydes, according to a two-step
one-pot reaction involving the formation of the imines 3
26
In summary, we have demostrated the utility of a wide
variety of N-tert-butanesulfinyl aldimines as acceptors in
intermolecular radical additions of alkyl iodides mediated
by Et3B/O2. The addition is highly diastereoselective
and mainly applicable to secondary and tertiary radicals,
although some primary radicals have been successfully
added. An efficient one-pot approach to the R-branched
sulfinamides, from the corresponding aldehydes, has
been described. The tolerance of functional groups and
the low restrictions to steric effects, allowing the efficient
incorporation of hindered alkyl groups, suggest these
radical additions as a synthetic alternative to the use of
organometallic reagents to prepare enantiopure func-
tionalized R-branched primary amines.
under BF3 OEt2 catalysis (instead of the usual CuSO4
)
3
and subsequent radical addition under our standard con-
ditions (Scheme 1).
To understand the stereochemical results of these
reactions, the stability of different conformers of the
N-tert-butanesulfinyl benzaldimine 3A was theoretically
studied at the DFT level.27 The conformational equili-
brium is shifted toward the rotamer displaying the sulfinyl
oxygen in the s-cis arrangement with respect to the CdN
(ΔG = 4.0 kcal/mol, Figure 1), with the hydrogen bond
O---HC being one of the most important factors in its
stabilization.28 According to these calculations, the ap-
proach of the radical to the less hindered re-face of imines
in their more stable A conformation could easily account
for the R configuration assigned to the obtained com-
pounds 5 (Figure 1).
Acknowledgment. Financial support by the Spanish
Government (Grant CTQ2012-35957) and Comunidad de
Madrid (CCG08-UAM/PPQ-4151 and S2009/PPQ1634)
is gratefully acknowledged. I.A. thanks Centro de
(25) The addition of benzyl zinc to aliphatic N-tert-butanesulfinyl
aldimines gave low dr (up to 77:23), in contrast to the high stereoselec-
tivity attained with the aromatic counterparts. See ref 14b.
(26) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A.
J. Org. Chem. 1999, 64, 1278.
(27) See SI for the details.
(28) Similar results, but lower ΔG values, had been obtained for the
N-benzenesulfinyl benzaldimine: Garcıa Ruano, J. L.; Torrente, E.; Alonso,
´
ꢀ
Computacion Cientıfica (UAM) for generous allocation
´
of computer time. J.A.F.-S. thanks Comunidad de Madrid
(S2009/PPQ1634) for a predoctoral contract. Dedicated to
Dr. M. Rosario Martın on the occasion of her retirement.
´
I.; Rodriguez, M.; Martın-Castro, A. M.; Degl’Innocenti, A.; Frateschi, L.;
´
Capperucci, A. J. Org. Chem. 2012, 77, 1974. Also see ref 12b.
(29) Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1999, 121, 268.
(30) The absolute configuration of the new chiral center at the major
diastereoisomer 5Aa has been established as R by the coincidence in the
specific rotation of amine hydrochloride 6Aa, with that previously
reported: Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron: Asymmetry
2008, 19 (603), 2484. Tentatively, the absolute configurations of major
sulfinamides 5 were assigned as R by analogy.
Supporting Information Available. Experimental pro-
cedures, characterization data, and theoretical calcula-
tions. This material is available free of charge via the
Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX