Synthesis of chiral N-sulfonyl and N-phosphinoyl α-halo aldimine precursors

Article abstract of DOI:10.1002/adsc.201200864

α-Halogenated aldimines have emerged as an important class of synthetic intermediates. The stability and reactivity of α-halo aldimines can vary greatly depending on the nitrogen protecting group. A general synthesis of stable, chiral α-halo-N-sulfonyl an

Full text of DOI:10.1002/adsc.201200864

FULL PAPERS
DOI: 10.1002/adsc.201200864
Synthesis of Chiral N-Sulfonyl and N-Phosphinoyl a-Halo
Aldimine Precursors
Gretchen R. Stanton,a Mehmet Gçllꢀ,a Rebecca M. Platoff,a Corinne E. Rich,a
Patrick J. Carroll,a and Patrick J. Walsha,*
a
P. Roy and Diana T. Vagelos Laboratories, University of Pennsylvania, Department of Chemistry, 231 South 34th Street,
Philadelphia, Pennsylvania 19104-6323, USA
Fax : (+1)-573-2875; e-mail: pwalsh@sas.upenn.edu
Received: September 26, 2012; Revised: December 10, 2012; Published online: February 25, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200864.
Abstract: a-Halogenated aldimines have emerged as mine precursor and the isolated aldimine can react
an important class of synthetic intermediates. The with an alkynyllithium nucleophile to give trans-b-
stability and reactivity of a-halo aldimines can vary chloroamine products with excellent dr. Ring closure
greatly depending on the nitrogen protecting group. affords the enantioenriched trans-aziridine, demon-
A general synthesis of stable, chiral a-halo-N-sulfon- strating the potential for this approach in complex
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
base. Enantioenriched a-chloro aldehydes can be Keywords: diastereoselectivity; halogenation; multi-
employed to afford aldimine precursors with no ero- component reactions; nitrogen heterocycles; synthet-
sion of optical purity. Both the enantioenriched aldi- ic methods
Introduction
is sulfinyl imines, which exhibit enhanced stability rel-
ative to their sulfonyl counterparts.
Enantioenriched nitrogen-containing molecules are
Based on the early work of Engerts and Strating,[7]
ubiquitous in natural products and other biologically a-amido sulfones have gained much attention as
active scaffolds. As a result, the stereoselective forma- stable, storable aldimine precursors in synthesis.[8] The
tion of nitrogen-bound carbon centers continues to be preparation of a-amido sulfone derivatives (1) in-
an important area in methods development.[1]
A
volves a three-component reaction of a suitable car-
common approach to access this structural motif is bamate or sulfonamide, aldehyde, and sodium sulfin-
nucleophilic addition of organometallic reagents to
ate under acidic conditions (Scheme 1).[7b,c,8] Later
ACHTUNGTRENNUNG
C=N double bonds with a-stereogenic centers.[2] Al- studies showed that the corresponding aldimine could
though the N-alkyl- and N-arylimine precursors to be isolated upon treatment of the amido sulfone
these additions are straightforward to prepare and 1 with a mild base.[9] More recently, Chemla and co-
store, they often suffer from low reactivity towards
nucleophiles. Alternatively, imines bearing electron-
withdrawing groups such as N-acyl,[3] N-sulfonyl,[4] N-
sulfinyl,[5] and N-phosphinoyl,[6] exhibit enhanced re-
activity. While imines prepared from aromatic alde-
hydes and primary amine derivatives bearing an elec-
tron-withdrawing group on the nitrogen are reasona-
bly stable, aliphatic aldimines undergo a facile hydrol-
ysis or self-condensation via tautomerization to the
corresponding enamines. Consequently, aliphatic ald-
ACHTUNGTRENNUNGimines with a-hydrogens are often generated and
trapped to circumvent these decomposition path-
ways.[4] One exception to this pronounced instability Scheme 1. Formation of a-amido sulfone 1.
Adv. Synth. Catal. 2013, 355, 757 – 764
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
757

Gretchen R. Stanton et al.
FULL PAPERS
Scheme 2. Previous routes to a-halogenated aldimines.
workers have utilized this two-step method to gener- chloro aldACTHNUTRGNEiNUG mines bearing an a-hydrogen en route to
ate N-sulfonyl aldimines from enolizable, aliphatic al- stereodefined b-lactams (Route B).[15] The b-lactam
dehydes.[10] It is noteworthy that bisulfite adducts products were afforded with 82–90% ee, showing min-
have been used in a similar manner to store unstable imal erosion of optical purity in a multi-step sequence
aldehydes.[11]
from readily available amino acids.
a-Halogenated aldimines have been known for
One drawback to the direct synthesis of more acti-
quite some time and represent a useful class of inter- vated a-chloro aldimines with an electron-withdraw-
mediates for the synthesis of aza-heterocycles includ- ing group on the nitrogen is the instability of the
ing aziridines, azetidines, and b-lactams.[12] Several formed aldimine. Hayashi and co-workers have dem-
methods for their syntheses are outlined in Scheme 2. onstrated the first examples of stable N-tosyl-a-chloro
De Kimpe and co-workers pioneered studies on the aldimine precursors (Scheme 2, Route C).[16] This
synthesis and reactivity of N-alkyl-a-chloro ald- amido sulfone, derived from chloro acetaldehyde, can
ACHTUNGTRENNUNG
imines.[13] Their approach involved the condensation be employed in one-pot reactions in which the aldi-
of a,a-disubstituted acetaldehydes with primary mine is formed in situ. However, other substituted a-
amines and subsequent chlorination of the resulting chloro aldehydes were not studied. We are aware of
aldimine with N-chlorosuccinimide (Route A).[13a] only one other example of conversion of amido sul-
This method was extended to include N-tosyl deriva- fone precursors to a-halo aldimines derived from
tives.[14] Enolizable N-alkyl-a-chloro aldimines (R1 or urea with a limited scope (Scheme 2, Route C).[17]
R2 =H) necessitated an alternate approach from a-
Despite key advancements in accessing a-halogen-
chloro aldehydes to circumvent the formation of di- ated aldimines and their broad applications, syntheses
chlorinated side products.[13a] De Kimpe has also ex- of a-halo-N-sulfonyl aldimines containing a hydrogen
plored the generation of enantioenriched, N-alkyl-a- at the a-stereogenic center are lacking. With this in
758
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 757 – 764

Synthesis of Chiral N-Sulfonyl and N-Phosphinoyl a-Halo Aldimine Precursors
Table 1. Optimization of the synthesis of N-tosyl sulfone
3a.[a]
Table 2. Synthesis of a-halo-N-tosyl aldimine precursors
under aqueous conditions.
[a]
Condtions a: 3 mL of H2O:HCO2H (1:1) were employed
per mmol of chloro aldehyde (0.33M). Condtions b:
1.5 mL of H2O:HCO2H (1:1) were employed per mmol
of chloro aldehyde (0.67M).
mind, we set out to prepare stable amido sulfone pre-
cursors to these aldimines. In particular, we aimed to
explore whether a practical approach to storable,
enantioenriched a-chloro aldimine precursors of type
1 could be achieved. We also demonstrate their utility
in the addition of two types of organometallic nucleo-
philes to the aldimines to afford useful enantioen-
riched building blocks.
Results and Discussion
[a]
1.5 mL of H2O:HCO2H (1:1) were employed per mmol
of chloro aldehyde (0.67M) using p-TolSO2Na. Ts=para-
Initially, we examined the reaction of 2-chlorooctanal,
p-toluenesulfonamide, and p-toluenesulfinic acid
sodium salt hydrate in aqueous formic acid. Conduct-
ing the reaction under conditions used for non-halo-
genated aldehydes by Chemla and co-workers[10] re-
sulted in poor conversions (Table 1, entries 1 and 2).
Significantly longer reaction times (3 and 5 days) fur-
nished the a-amido sulfone product 3a with increased
yield (up to 80%, entries 3 and 4). We were pleased
toluenesulfonyl.
The dr was determined by analysis of 1H NMR spectra.
Reaction conducted on a 15-mmol scale
Major diastereomer determined to be syn by X-ray anal-
ysis.
[b]
[c]
[d]
to find that employing more concentrated reaction action in entry 2 was conducted under aqueous condi-
conditions (0.33M to 0.67M with respect to the alde- tions using p-toluenesulfonamide on a 15-mmol scale,
hyde) further improved the yield to 85% and reduced the a-amido sulfone product was obtained in 75%
the reaction time to 72 h (entry 5). As shown in yield. Both a-bromo and a-fluoro aldehydes also
entry 6, a longer reaction time did not increase the were amenable to the method (entries 6 and 7).
yield and, therefore, we used the conditions in entry 5
to proceed with our studies.
With synthetic methods in place to prepare the a-
chloro-N-tosyl aldimine precursors, we focused on de-
The optimized reaction conditions in Table 1 termination of their stereochemistry. As illustrated in
(entry 5) were applied to a variety of aliphatic a- Figure 1, the relative stereochemistry of 3e was deter-
chloro aldehydes (Table 2). Both a terminal olefin mined to be syn as ascertained by X-ray analysis. The
and a silyl protected b-hydroxy group were tolerated high level of diastereoselectivity seen in the formation
under the reaction conditions (entries 4 and 5). The of 3e (Table 2, entry 5) can be attributed to a favora-
a-amido sulfone products were afforded in good to ble hydrogen bonding interaction between the a-
excellent yields (64–90%). Of significance, these chloro moiety and the protonated N-sulfonyl imine.
imine precursors can be generated on a multi-gram Petrini and co-workers have observed similar stereo-
scale in comparable yields. For example, when the re- chemical outcomes in their synthesis of a-amido sul-
Adv. Synth. Catal. 2013, 355, 757 – 764
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
759

Gretchen R. Stanton et al.
FULL PAPERS
Figure 1. X-ray crystal structure of amido sulfone 3e and proposed transitions state to account for observed stereochemistry.
fones from chiral a-alkoxy and a-amidoalkyl alde- when (S)-2-chlorooctanal was used. Similarly, amido
hydes.[18] In a series of computational studies, they sulfone (À)-3d was furnished with 96% ee.
found that the preferred conformation of the N-acyli-
For substrates prone to a small equilibrium con-
um ion intermediate was stabilized by an electrostatic stant in favor of the iminium ion over sulfone 1 in
interaction between the NH and the a-alkoxy or a- water (Scheme 1), we envisioned a second set of con-
amido group in a similar fashion to that shown in ditions in organic solvents.[20] When dichloromethane
Figure 1.
was used as a solvent, comparable or improved yields
Several elegant processes have been developed to were achieved in most cases (Table 3). Unfortunately,
synthesize enantioenriched a-chloro aldehydes.[19] To enantioenriched a-chloro aldehydes suffered consider-
demonstrate the synthetic utility of our method, we able erosion of ee using this method. A crucial differ-
examined the compatibility of enantioenriched a- ence between the aqueous and dichloromethane reac-
chloro aldehydes with the aqueous reaction condi- tion conditions is that under the aqueous conditions,
tions. Gratifyingly, employing (R)-2-chlorooctanal[19b] the a-chloro aldehydes are insoluble and, therefore,
of 96% ee provided amido sulfone (À)-3a with no less susceptable to racemization. In dichloromethane,
erosion of ee (Scheme 3). Interestingly, in contrast to the reactions are homogeneous and it is likely that
the reaction using the racemic aldehyde (Table 2, the p-TolSO2À promotes racemization.
entry 1), the product was generated with >20:1 dr
It is worth noting that the corresponding N-tosyl-a-
(Scheme 3). A single diastereomer was also isolated chloro aldimine can be isolated in excellent yield
upon treatment of a-amido sulfone 3a with a mild
base (Scheme 4).[9,10] Aldimine 4 is stable at room
temperature for several hours for use in subsequent
reactions. Unfortunately, aldimines derived from
more functionalized precursors such as 3c and 3e are
very unstable, showing significant amounts of hydroly-
sis within an hour.
We next surveyed the substrate scope with respect
to the protecting group on nitrogen. As illustrated in
Table 4, a variety of N-sulfonyl sulfone derivatives
can be synthesized in moderate to good yield (en-
tries 1–4). Sulfonyl protecting groups[21] that are re-
Scheme 3. Formation of enantioenriched amido sulfones.
moved under mild conditions, such as Bs, Nos, and 2-
760
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 757 – 764

Synthesis of Chiral N-Sulfonyl and N-Phosphinoyl a-Halo Aldimine Precursors
Table 3. Synthesis of a-chloro N-tosyl aldimine precursors in
organic solvent.
Table 4. Synthesis of other a-chloro-N-sulfonyl aldimine pre-
cursors.
[a]
1
The dr was determined by analysis of H NMR spectra.
Ms=methanesulfonyl, Bs=para-bromobenzenesulfonyl,
Nos=para-nitrobenzenesulfonyl.
[a]
Reaction conducted in CH2Cl2 under a nitrogen atmos-
phere using p-TolSO2H.
[b]
The dr was determined by analysis of 1H NMR spectra.
[b]
[c]
1.5 mL of H2O:HCO2H (1:1) were employed per mmol
of chloro aldehyde (0.67M) using p-TolSO2Na.
Reaction conducted in CH2Cl2 under a nitrogen atmos-
phere using p-TolSO2H.
thienyl,[22] were good substrates for this transforma-
tion. The sulfinic acid moiety can also be modified,
further demonstrating the tunability of the precursors
for one-pot/tandem reaction design (entry 5).
To demonstrate the synthetic utility of our a-chloro
N-Phosphinoyl imines have emerged as a useful aldimines, we next identified several applications of
class of electrophiles in organic synthesis.[6,23] How- the a-chloro aldimine precursors. Stereodefined
ACHTUNGTRENNUNGever, we are not aware of any examples of N-phosphi- alkynACHTUNGTRENNyUGN laziridines are valuable scaffolds and several
noyl imines containing an a-halo group. The advant-
age of phosphinamides is that the phosphinoyl group
can be removed under fairly mild reaction conditions.
We examined the reaction of diphenylphosphinamide
with 2-chloroisovaleraldehyde and p-toluenesulfinic
acid. Phosphinamido sulfone 6a was furnished in 61%
yield as a single diastereomer (Scheme 5). Other
simple alkyl-substituted a-chloro aldehydes were suit-
able in the reaction.
Scheme 4. a-Chloro aldimine formation.
Scheme 5. Synthesis of N-phosphinoyl aldimine precursors
Adv. Synth. Catal. 2013, 355, 757 – 764
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
761

Gretchen R. Stanton et al.
FULL PAPERS
excellent methods for their synthesis have been devel-
oped.[24] We conceived a complementary, one-pot re-
action in which an excess of the organometallic re-
agent could be used to generate the aldimine in situ.
Towards this end, enantioenriched amido sulfone
(+)-3a was reacted with excess lithium TMS-acety-
lide[25] to give b-chloroamine 7 in 85% yield as
a single diastereomer (Scheme 6). Subsequent ring
closure under mild conditions provided trans-aziridine
8 with 95% ee in 96% yield. Alternatively, aldimine 4
was isolated after treatment with NaHCO3 (94%
yield) and reacted with 1.2 equivalents of lithium
TMS-acetylide to give 7 in comparable yield and dr.
The relative stereochemistry was confirmed by exami-
nation of the aziridine H-1/H-2 coupling constant (J=
4.5 Hz). The high anti-selectivity of the addition step
can be rationalized by the Cornforth–Evans stereoin-
duction models.[26] Other models have also been pro-
posed for additions to a-halogenated carbonyl deriva-
tives.[27] It is worth noting that Hilmersson and co-
workers have recently disclosed a new method for the
deprotection of tosyl amides under mild reaction con-
ditions.[28] These conditions were shown to be compat-
ible with aziridine substrates. Highly functionalized
aziridine 8 can potentially be used to prepare aziri-
dine-2-carboxylic acid derivatives. These important
building blocks have been widely applied in the syn-
thesis of amino acid and peptide derivatives.[29]
Scheme 6. Synthesis of enantioenriched trans-alkynylaziri-
dines
Recently we have been interested in the addition of
organometallic nucleophiles to chiral aldehydes and
ketones with substituents on the a- or b-carbons that
traditionally do not coordinate to metals and there-
fore undergo Felkin addition.[30] In this work, we dem-
onstrated that a- and b-silyloxy aldehydes and a-silyl-
ACHTUNGTRENNUNGoxy ketones undergo chelation-controlled addition of
a wide range of organozinc nucleophiles in the pres-
ence of alkylzinc halides and sulfonates, RZnX and
RZnOSO2RF.[31] With this work in mind, we investi-
gated several other applications of our a-halo ald-
ACHTUNGTRENNUNGimine precursors (Scheme 7). We have recently dis-
closed a new one-pot route to yield syn-b-chloro allyl-
ic amines such as 9 with excellent dr favoring the un-
precidented chelation-controlled product [Eq. (1)].[32]
Allylic amines constitute an important class of inter-
mediates in synthesis.[33] In the current work, we
sought to explore the utility of the highly functional-
ized syn-b-chloro allylic amine products in multi-step
and tandem reactions. Chloroamine 9 was used in
a two-step sequence to generate cis-aziridine-2-car-
boxaldehyde 10 in 83% yield via ring closure followed
by ozonolysis [Eq. (2)]. Stereodefined aziridine-2-car-
bonyl derivatives are known to undergo directed nu-
cleophilic additions using organometallic reagents
with high diastereoselectivity.[34] Furthermore, chloro-
amine 9 was applied in a tandem ring closure/palladi-
um-catalyzed allylic substitution reaction [Eq. (3)].
Scheme 7. Applications of syn-b-chloro allylic amines.
762
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 757 – 764

Synthesis of Chiral N-Sulfonyl and N-Phosphinoyl a-Halo Aldimine Precursors
Allylic amine 11 was obtained as a single regioisomer General Procedure for the Formation of N-
and a mixture of diastereomers (dr~10:1).
Phosphinoyl Aldimine Precursors
A dry 10-mL round-bottom flask, which was purged with ni-
trogen, was charged with diphenylphosphinamide (217 mg,
1 mmol), p-toluenesulfinic acid (234 mg, 1. mmol), a-chloro
aldehyde (1.5 mmol) and dry Et2O (6 mL). The reaction
mixture was allowed to stir at room temperature until com-
plete as determined by TLC (72 h), upon which the solid
product precipitated out of the solution. The solid product
was collected onto a sintered glass filter and washed sequen-
tially with Et2O to remove the excess aldehyde. Most prod-
ucts can be used in subsequent reactions without further pu-
rification. Products of higher purity can be obtained by re-
crystallization from EtOAc/hexanes.
Conclusions
In summary, facile routes to chiral N-sulfonyl-a-halo
aldimine precursors have been developed. Additional-
ly, we have expanded the scope of this method to in-
clude N-phosphinoyl-a-chloro aldimine adducts. We
have demonstrated that enantioenriched a-chloro al-
dehydes are compatible with aqueous reaction condi-
tions, giving rise to a-amido sulfone products with no
erosion of ee. These stable precursors can be utilized
in one-pot aldimine formation/diastereoselective addi-
tion reactions to access trans-alkynylaziridines, cis-
aziridine-2-carboxaldehyde derivatives, and g-func-
tionalized allylic amines.
Supporting Information
Supporting Information for this article, including reaction
procedures, compound characterization and NMR spectra, is
available. CCDC 882573 contains the crystallographic data
for compound 3e. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Experimental Section
General Procedure for the Formation of N-Sulfonyl
Aldimine Precursors Under Aqueous Conditions
To a 10-mL round-bottom flask was added a-chloro alde-
hyde (1.5 mmol) followed by deionized water (1.2 mL), p-
toluenesulfonamide (171 mg, 1 mmol), and p-toluenesulfinic
acid sodium salt monohydrate (267 mg, 1.5 mmol). Formic
acid (1.2 mL) was subsequently added, and the reaction mix-
ture was stirred at room temperature for 72 h. The resulting
solid was filtered through a sintered glass funnel. The solid
was washed thoroughly with water (3ꢂ10 mL) and hexanes
(5ꢂ10 mL). The solid was then collected, dissolved in
CH2Cl2 (25 mL) and filtered through celite. The filtrate was
concentrated and dried under vacuum for several hours.
Most products can be used in subsequent reactions without
further purification. Products of higher purity can be ob-
tained by recrystallization from EtOAc/hexanes.
Acknowledgements
We thank the NSF (CHE-0848467 and 1152488) for partial
support of this work. G.R.S thanks UNCF-Merck and
NOBCChE/GlaxoSmithKline programs, ACS Organic Divi-
sion, and Amgen for graduate scholarships. M.G. thanks TU-
BITAK for graduate scholarships.
References
[1] a) E. J. Corey, X.-M. Cheng, The Logic of Chemical
Synthesis, Wiley, New York, 1989; b) K. C. Nicolaou,
E. J. Sorensen, Classics in Total Synthesis, VCH, Wein-
heim, 1996.
[2] a) A. H. Hoveyda, D. A. Evans, G. C. Fu, Chem. Rev.
1993, 93, 1307–1370; b) E. M. Carreira, L. Kvaerno,
Classics in Stereoselective Synthesis, Wiley-VCH, Wein-
heim, 2009; c) R. Bloch, Chem. Rev. 1998, 98, 1407–
1438; d) S. Kobayashi, Y. Mori, J. S. Fossey, M. M.
Salter, Chem. Rev. 2011, 111, 2626–2704.
[3] M. Petrini, E. Torregiani, Synthesis 2007, 159–186.
[4] S. M. Weinreb, Top. Curr. Chem. 1997, 190, 131–184.
[5] a) J. A. Ellman, T. D. Owens, T. P. Tang, Acc. Chem.
Res. 2002, 35, 984–995; b) F. Ferreira, C. Botuha, F.
Chemla, A. Perez-Luna, Chem. Soc. Rev. 2009, 38,
1162–1186; c) F. A. Davis, V. Srirajan, D. D. Titus, J.
Org. Chem. 1999, 64, 6931–6934; d) B. Denolf, S. Man-
gelinckx, K. W. Tçrnroos, N. De Kimpe, Org. Lett.
2006, 8, 3129–3132; e) M. Robak, M. A. Herbage, J. A.
Ellman, Chem. Rev. 2010, 110, 3600–3740.
General Procedure for the Formation of N-Sulfonyl
Aldimine Precursors in Dichloromethane
A dry 10-mL round-bottom flask, which was purged with ni-
trogen, was charged with p-toluenesulfonamide (171 mg,
1 mmol), p-toluenesulfinic acid (187 mg, 1.2 mmol), a-chloro
aldehyde (1.5 mmol) and CH2Cl2 (4 mL). MgSO4 was added
to the flask and the reaction mixture was allowed to stir at
room temperature until complete as determined by TLC
(24–48 h). The mixture was diluted with CH2Cl2 (20 mL), fil-
tered through celite, and concentrated under vacuum. The
solid product was collected onto a sintered glass filter and
washed sequentially with hexanes (5ꢂ10 mL) to remove the
excess aldehyde. Most products can be used in subsequent
reactions without further purification. Products of higher
purity can be obtained by recrystallization from EtOAc/hex-
anes.
[6] S. M. Weinreb, R. K. Orr, Synthesis 2005, 1205–1227.
[7] a) J. B. F. N. Engberts, J. Strating, Recl. Trav. Chim.
1964, 83, 733–736; b) J. B. F. N. Engberts, J. Strating,
Recl. Trav. Chim. 1965, 84, 942–950; c) J. B. F. N. Eng-
Adv. Synth. Catal. 2013, 355, 757 – 764
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
763

Gretchen R. Stanton et al.
FULL PAPERS
berts, T. Olijnsma, J. Strating, Recl. Trav. Chim. 1966,
85, 1211–1222; d) T. Olijnsma, J. B. F. N. Engberts, J.
Strating, Recl. Trav. Chim. 1967, 86, 463–473; e) T.
Olijnsma, J. B. F. N. Engberts, J. Strating, Recl. Trav.
Chim. 1972, 91, 209–212; f) H. Meijer, R. M. Tel, J.
Strating, J. B. F. N. Engberts, Recl. Trav. Chim. 1973, 92,
72–82.
Bachmann, M. Marigo, K. A. Jørgensen, J. Am. Chem.
Soc. 2004, 126, 4790–4791.
[20] a) M. Enrico, T. Mecozzi, M. Petrini, J. Org. Chem.
2002, 67, 2989–2994; b) T. Mecozzi, M. Petrini, R. Pro-
feta, Tetrahedron: Asymmetry 2003, 14, 1171–1178.
[21] P. G. M. Wuts, T. W. Greene, Greeneꢀs Protective
Groups in Organic Synthesis, 4th edn., Wiley, Hoboken,
NJ, 2007.
[8] M. Petrini, Chem. Rev. 2005, 105, 3949–3977.
[9] A. M. Kanazawa, J.-N. Dennis, A. E. Greene, J. Org.
Chem. 1994, 59, 1238–1240.
[10] F. Chemla, V. Hebbe, J.-F. Normant, Synthesis 2000,
75–77.
[11] a) P. G. M. Wuts, C. L. Bergh, Tetrahedron Lett. 1986,
27, 3995–3998; b) M. Seki, M. Hatsuda, S. Yoshida, Tet-
rahedron Lett. 2004, 45, 6579–6581; c) M. Seki, M. Hat-
suda, Y. Mori, S. Yoshida, S. Yamada, T. Shimizu,
Chem. Eur. J. 2004, 10, 6102–6110; d) M. He, B. J.
Beahm, J. W. Bode, Org. Lett. 2008, 10, 3817–3820.
[12] a) S. Mangelinckx, N. Giubellina, N. De Kimpe, Chem.
Rev. 2004, 104, 2353–2399; b) A. K. Yudin, Aziridines
and Epoxides in Organic Synthesis, Wiley, Weinheim,
2006; c) N. De Kimpe, The Chemistry of a-Haloke-
tones, a-Haloaldehydes, and a-Haloimines, Wiley, New
York, 1988.
[22] A. Salvador Gonzꢆlez, R. Gꢇmez Arrayꢆs, J. C. Carre-
tero, Org. Lett. 2006, 8, 2977–2980.
[23] a) C. Jimeno, K. S. Reddy, L. Solꢈ, A. Moyano, M. A.
Pericꢈs, A. Riera, Org. Lett. 2000, 2, 3157–3159; b) A.
Cꢉtꢃ, A. A. Boezio, A. B. Charette, Proc. Natl. Acad.
Sci. USA 2004, 101, 5405–5410.
[24] a) F. Chemla, F. Ferreira, J. Org. Chem. 2004, 69, 8244–
8250; b) F. Ferreira, M. Audouin, F. Chemla, Chem.
Eur. J. 2005, 11, 5269–5278.
[25] a) B. Kang, R. Britton, Org. Lett. 2007, 9, 5083–5086;
b) J. Mowat, R. Gries, G. Khaskin, G. Gries, R. Britton,
J. Nat. Prod. 2009, 72, 772–776.
[26] a) D. A. Evans, S. J. Siska, V. J. Cee, Angew. Chem.
2003, 115, 1803–1807; Angew. Chem. Int. Ed. 2003, 42,
1761–1765; b) V. J. Cee, C. J. Cramer, D. A. Evans, J.
Am. Chem. Soc. 2006, 128, 2920–2930.
[13] a) N. De Kimpe, R. Verhꢃ, L. De Buyck, H. Hasma, N.
Schamp, Tetrahedron 1976, 32, 2457–2466; b) N. De
Kimpe, R. Verhꢃ, L. De Buyck, H. Hasma, N. Schamp,
Tetrahedron 1976, 32, 3063–3067; c) D. De Kimpe, R.
Verhꢃ, L. De Buyck, N. Schamp, J. Org. Chem. 1977,
42, 3704–3708; d) N. De Kimpe, R. Verhe, L. De
Buyck, N. Schamp, Recueil J. Royal Netherlands Chem.
Soc. 1977, 242–246; e) N. De Kimpe, R. Verhꢃ, L. De
Buyck, N. Schamp, M. Charpentier-Morize, Tetrahe-
dron Lett. 1982, 23, 2853–2856; f) N. De Kimpe, E. Sta-
noeva, R. Verhꢃ, N. Schamp, Synthesis 1988, 587–592.
[14] L. Kiss, S. Mangelinckx, R. Sillanpꢄꢄ, F. Fꢀlçp, N. De
Kimpe, J. Org. Chem. 2007, 72, 7199–7206.
[15] a) M. D’Hooghe, W. Van Brabandt, S. Dekeukeleire, Y.
Dejaegher, N. De Kimpe, Chem. Eur. J. 2008, 14, 6336–
6340; b) S. Dekeukeleire, M. Dꢅhooghe, K. W. Tçrn-
roos, N. De Kimpe, J. Org. Chem. 2010, 75, 5934–5940.
[16] Y. Hayashi, T. Urushima, D. Sakamoto, K. Torii, H.
Ishikawa, Chem. Eur. J. 2011, 17, 11715–11718.
[27] a) T. Borg, J. Danielsson, P. Somfai, Chem. Commun.
2010, 46, 1281–1283; b) T. Borg, J. Danielsson, M.
Mohiti, P. Restorp, P. Somfai, Adv. Synth. Catal. 2011,
353, 2022–2036.
[28] T. Anker, G. Hilmersson, Org. Lett. 2009, 11, 503–506.
[29] a) K. Okawa, K. Nakajima, Biopolymers 1981, 20,
1811–1821; b) A. Korn, S. Rudolph-Bçhner, L. Morod-
´
er, Tetrahedron 1994, 50, 1717–1730; c) D. P. Galonic,
N. D. Ide, W. A. van der Donk, D. Y. Gin, J. Am.
Chem. Soc. 2005, 127, 7359–7369.
[30] A. Mengel, O. Reiser, Chem. Rev. 1999, 99, 1191–1224.
[31] a) G. R. Stanton, C. N. Johnson, P. J. Walsh, J. Am.
Chem. Soc. 2010, 132, 4399–4408; b) G. R. Stanton, G.
Koz, P. J. Walsh, J. Am. Chem. Soc. 2011, 133, 7969–
7976; c) G. R. Stanton, M. C. Kauffman, P. J. Walsh,
Org. Lett. 2012, 14, 3368–3371; d) H. Li, P. J. Carroll,
P. J. Walsh, J. Am. Chem. Soc. 2008, 130, 3521–3531;
e) S.-J. Jeon, E. L. Fisher, P. J. Carroll, P. J. Walsh, J.
Am. Chem. Soc. 2006, 128, 9618–9619; f) M. H. Kerri-
gan, S.-J. Jeon, Y. K. Chen, L. Salvi, P. J. Carroll, P. J.
Walsh, J. Am. Chem. Soc. 2009, 131, 8434–8445.
[32] G. R. Stanton, P.-O. Norrby, P. J. Carroll, P. J. Walsh, J.
Am. Chem. Soc. 2012, 134, 17599–17604.
[17] N. N. Kurochkin, A. A. Fesenko, D. A. Cheshkov,
M. M. Davudi, A. D. Shutalev, Tetrahedron Lett. 2011,
52, 88–91.
[18] E. Foresti, G. Palmieri, M. Petrini, R. Profeta, Org.
Biomol. Chem. 2003, 1, 4275–4281.
[33] M. Johannsen, K. A. Jørgensen, Chem. Rev. 1998, 98,
1689–1708.
[34] A. Kulshrestha, J. M. Schomaker, D. Holmes, R. J. Sta-
ples, J. E. Jackson, B. Borhan, Chem. Eur. J. 2011, 17,
12326–12339.
[19] a) M. P. Brochu, S. P. Brown, D. W. C. MacMillan, J.
Am. Chem. Soc. 2004, 126, 4108–4109; b) M. Amatore,
T. D. Beeson, S. P. Brown, D. W. C. MacMillan, Angew.
Chem. 2009, 121, 5223–5226; Angew. Chem. Int. Ed.
2009, 48, 5121–5124; c) N. Halland, A. Braunton, S.
764
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 757 – 764