Stereodivergent synthesis of functionalized tetrahydropyrans accelerated by mechanism-based allylboration and bioinspired oxa-michael cyclization

Article abstract of DOI:10.1002/anie.201600558

A stereodivergent strategy enabled by bioinspired oxa-Michael cyclization was developed for the synthesis of functionalized tetrahydropyrans on the basis of the inherent symmetry in 1,3-diols, the symmetries of which were tunable by stereoselective hydroboration of an allene with a variety of alkylborane reagents and subsequent allylation of an aldehyde. The mechanism-based utilization of monoalkyl borane in the hydroboration and allylation cascade is unprecedented. Symmetry breakdown: The thermodynamic and kinetic hydroboration of allenes and subsequent allylboration provide a key stereodefinable module with a latent symmetry. Following a deprotection/chain elongation/oxa-Michael cyclization sequence, the stereocogeners of highly functionalized tetrahydropyrans were synthesized for rapid access to structural motifs found in bioactive polyketides.

Full text of DOI:10.1002/anie.201600558

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201600558
German Edition: DOI: 10.1002/ange.201600558
Tetrahydropyranes
Stereodivergent Synthesis of Functionalized Tetrahydropyrans
Accelerated by Mechanism-Based Allylboration and Bioinspired
Oxa-Michael Cyclization
Lin Yang, Zuming Lin, Sha-Hua Huang,* and Ran Hong*
Abstract: A stereodivergent strategy enabled by bioinspired
oxa-Michael cyclization was developed for the synthesis of
functionalized tetrahydropyrans on the basis of the inherent
symmetry in 1,3-diols, the symmetries of which were tunable by
stereoselective hydroboration of an allene with a variety of
alkylborane reagents and subsequent allylation of an aldehyde.
The mechanism-based utilization of monoalkyl borane in the
hydroboration and allylation cascade is unprecedented.
F
unctionalized tetrahydropyrans (THPs) are recurring
motifs in numerous biologically significant natural products,
such as lasonolide A (1), ambruticin S (2), and pederin (3)
[
1]
(
Figure 1a). A pyran-cyclase-catalyzed oxa-Michael reac-
[2]
tion was proposed to construct THPs, although the detailed
enzymology remains unknown. The past several decades
have seen a variety of synthetic methods for the efficient
[
3]
[
4]
construction of THPs. For instance, during the synthesis of
lasonolide A (1), a potent anticancer marine natural product,
[5]
the methods used to access the THP ring were diverse. The
known approaches, however, face the challenge of stereo-
diversification of the four stereogenic centers in each THP,
and would be detrimental when a structure–activity relation-
ship (SAR) study is undertaken. With our continued interest
in polyketide synthesis, we became aware of a general
approach to access all stereoisomers of substituted THPs.
This strategy should meet several criteria: 1) a flexible
method to access three contiguous chiral centers with good
stereoselectivity; 2) facile accessibility of both cis- and trans-
stereoisomers of THP; and 3) a short and reliable synthetic
route. To this end, the A ring bearing a quaternary carbon
center in the lasonolides was selected to demonstrate the
generic and rapid access to the stereovariants of the hydro-
pyran ring.
Figure 1. a) Tetrahydropyrans in selected polyketides (highlighted in
grey; carbon atom numbering adapted from the original assignment).
b) An illustration of oxa-Michael cyclization (anti,anti-4 as example).
1
2
P, P , P =protecting groups, EWG=electron withdrawing group.
alkenes were preinstalled at C23 and C7. An inherent
symmetry in such THPs further guided us to design the
skipped polyol 4, which bears substituents at the central
[6]
1
We envisioned that a bioinspired oxa-Michael addition
would simplify the construction of two hydropyrans in
lasonolide A and its congeners if two electron-deficient
carbon atom and different distal protecting groups (e.g., P
2
and P ; Figure 1b). Accordingly, stereovariants of a given
THP were envisioned to be constructed by propagation of
a latent symmetry element through processing of the terminal
1
2
functional groups (OP or OP ) by means of a bioinspired
oxa-Michael cyclization. The access would rely on the
selective installation of a,b-unsaturated esters on either the
left or right side of 4 to allow the late Michael addition to
occur.
To begin with, the first level of synthesis would require
a stereodefinable allylation initiated from the hydroboration
of the allene 5 to access all possible diastereoisomers of 4
[
*] L. Yang, Z. Lin, Prof. Dr. S.-H. Huang, Prof. Dr. R. Hong
CAS Key Laboratory of Synthetic Chemistry of Natural Substances,
Shanghai Institute of Organic Chemistry (CAS)
3
45 Lingling Road, Shanghai 200032 (China)
E-mail: rhong@sioc.ac.cn
Homepage: honggroup.sioc.ac.cn
Prof. Dr. S.-H. Huang
School of Chemical and Environmental Engineering
Shanghai Institute of Technology
(
Scheme 1). It was known that 9-borabicyclo[3.3.1]nonane (9-
BBN) would deliver syn,syn-4a with good diastereoselectivity
84% yield, d.r. 10:1) via an E-allylborane, which is derived
from thermodynamic hydroboration of the allene (408C for
1
00 Haiquan Road, Shanghai 201418 (China)
E-mail: shahua@sit.edu.cn
(
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201600558.
6
280
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 6280 –6284

Angewandte
Communications
Chemie
Table 1: Sequential hydroboration and allylation with monoalkyl bora-
[a]
nes.
[b]
[c]
[d]
Entry Borane (equiv)
T [8C]
Conv [%]
Yield [%]
d.r.
1
2
3
4
5
(À)-IpcBH (2.0) 0!RT
77 (4 h)
>95 (1.4 h)
>95 (4 h)
>95 (2 h)
75 (4 h)
43
n.d.
45
70
n.d.
2.5:1
1.7:1
4.5:1
4.0:1
3.2:1
2
(+)-IpcBH
2
(2.0)
0
0
0
0
ThexBH (2.0)
2
ThexBH (1.3)
2
ThexBH (1.1)
2
[
a] Reaction conditions: (R)-6 (0.73 mmol), aldehyde 7 (1.5 equiv),
1
CH Cl (1.4 mL). [b] Conversion was determined by H NMR spectros-
2
2
copy in CDCl ; the reaction time (hours) is given within parentheses.
3
[
c] Yield of isolated product. [d] Ratio of the major diastereomer to minor
1
diastereomers. Determined by H NMR spectroscopy in CDCl .
3
n.d.=not determined.
Scheme 1. Stereochemical rationale of allylboration with E- and Z-
allylborane derived from thermodynamic and kinetic conditions,
respectively. Bn=benzyl, TBDPS=tert-butyldiphenylsilyl, TBS=tert-
butyldimethylsilyl.
[
11]
hydroboration with monoalkyl borane, a freshly liberated
(À)-IpcBH was quickly subjected to the subsequent hydro-
2
[12]
boration of the allene 6, and then the aldehyde 7 was added
at 08C (Table 1). The allylboration proceeded smoothly to
deliver the desired anti,syn-4c in 43% yield (77% conver-
[7,8]
4
h) (Scheme 1a).
Although bis(cyclohexyl)borane
(
Chx BH) was effective in the work of Ariza and co-workers
sion) after work-up (entry 1). The antipode of (À)-IpcBH
2
2
for the preparation of simpler anti,anti-1,3-diols in a kinetic
resulted in the desired product in a lower diastereoselectivity
(d.r. 1.7:1), but the reaction proceeded at a faster rate
(entry 2). Further optimization revealed that in situ generated
[
9]
fashion (08C, 3 h), the hydroboration of the 5 was slow, and
at an elevated temperature formation of syn,syn-4a increased
because of the increased presence of the E-allylborane arising
from a 1,3-boratropic shift.
other boranes and varying the reaction parameters (see the
2,3-dimethyl-2-butylborane (ThexBH ) was a superior mono-
2
[10]
Fortunately, upon surveying
alkyl borane reagent and delivered anti,syn-4c in good
diastereoselectivity (d.r. 4:1; entry 4). Although the selectiv-
ity could be slightly increased, the low yields of the isolated
products indicated the occurrence of side reactions when
2 equivalents of ThexBH2 was used (entry 3). Additional
decrease in the amount of borane only resulted in lower
conversion and selectivity (entry 5). Although reaction con-
ditions remain to be optimized, this unprecedented chemistry
allowed us to isolate the desired stereotriad in 70% yield
(entry 5). The possible syn-pentane interaction and gauche
effect enforce the equatorial alkyl chain of 7 to stay in an axial
position as shown in TS* (Scheme 2), and thus favorably
[8]
Table S2 in the Supporting Information), disiamylborane
Sia BH) was identified as a superior kinetic borane reagent
(
2
to afford anti,anti-4b, via a favorable transition state with Z-
allylborane (TS2 in Scheme 1b), in 90% yield and excellent
diastereoselectivity (d.r. > 15:1).
Access to either anti,syn-4c or syn,anti-4d was not nearly
as facile as that of the two previously described diastereomers.
Mechanistically, during the hydroboration of the kinetically
formed Z-allylborane, the severe 1,3-diaxial interaction
2
between the alkyl chain R and the R’ in borane enforces an
equatorial R in the favorable transition state, which gives
2
[13]
affords anti,syn-4c.
anti,anti-4b (Scheme 1b). However, for the formation of
anti,syn-4c, the R group should reside at the axial position
Given the encouraging allylboration to access distereo-
isomers of 1,3-diols, more alkyl aldehydes were preliminarily
surveyed (Table 2). Generally good to excellent d.r. values
2
during the allylation via TS* (Scheme 2), in which the
1
,3
detrimental A strain could be attenuated by introducing
a less sterically hindered group (X) on the borane. Hydrogen
is certainly an ideal alternative. Inspired by the Brown
were achieved with Sia BH (4ba–bc). The previously unfav-
2
orable anti,syn isomer obtained with a monoalkyl borane in
moderate selectivity remains valuable although further opti-
mization is needed (4ca–cc).
With a–c in hand, the subsequent removal of the benzyl
[14]
group in anti,anti-4b by the Liu-Shia protocol gave the diol
[15]
8
(Scheme 3), which was subjected to the Vat›le one-pot
TEMPO/BAIB oxidation and Wittig olefination to afford the
ester 10 in 81% yield (E/Z 20:1). The subsequent oxa-
Michael cyclization in the presence of p-tolylsulfonic acid
(
pTSA) delivered the desired cis-THP 11ba, whose stereo-
Scheme 2. Proposed transition states for anti,syn-4c with Z-allylborane:
syn-pentane interaction and gauche interaction versus 1,3-diaxial
interaction.
[16]
genicity was unambiguously established by X-ray analysis.
The compound 12 was isolated in 82% yield as a single isomer
Angew. Chem. Int. Ed. 2016, 55, 6280 –6284
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
6281

Angewandte
Communications
Chemie
Table 2: Allylboration of other alkyl aldehydes with Sia BH and
ThexBH2.
diastereoselectivity for the cyclization of the Z-configured
a,b-unsaturated ester 12 indicated an alternative mechanism
may occur, and differs from an allylic cationic species as is
generally adopted in precedented Brønsted acid promoted
2
[
a]
[4e, 6b]
oxa-Michael cyclizations.
It is assumed that a boatlike or
twist boatlike transition state might be feasible so that all
bulky groups reside in equatorial positions as compared to the
chairlike conformation, which may be destabilized by severe
steric repulsions (Figure 2).
Figure 2. Proposed pathway for acid-promoted oxa-Michael cyclization.
[
a] The above reactions were conducted with Sia BH and ThexBH under
2 2
The inherent s-symmetry in anti,anti-4b would enable
a reversed oxa-Michael addition to generate a stereoisomer of
1ba if the deprotection process could be readily altered.
the optimal reaction conditions described in the Supporting Information.
b] Yield is that of the isolated pure product.
[
1
With this notion in mind, a complete removal of two silyl
groups and simultaneous formation of the acetonide gave the
[
8]
1
,3-dioxane 13 in excellent yield (Scheme 4). The following
one-pot oxidation and olefination smoothly afforded the E-
configured a,b-unsaturated ester 14 in 94% yield. Finally, the
aforementioned protocol for the oxa-Michael cyclization
proved to be reliable to give the cis-THP 11bc as the major
stereoisomer (d.r. > 14:1) in just four steps and 69% overall
yield from (R)-6. The four stereocenters of 11bc were
identical to the A ring (from C19 to C23) in 1. The vinyl
Scheme 3. Construction of the cis-THP 11ba and trans-THP 11bb:
a) Sia BH (2.5 equiv), CH Cl , 08C, 3 h; 7 (1.5 equiv), À788C, 3 h, d.r.
2
2
2
1
5:1, 90% for anti,anti-isomer 4b; b) lithium (12.0 equiv), naphthalene
(
(
16.0 equiv), THF, À408C, 1.5 h, quant.; c) TEMPO (0.1 equiv), BAIB
1.2 equiv), CH Cl , RT, 5 h; then 9a (1.5 equiv), RT, E/Z>20:1, 90%
2
2
for (E)-10; d) pTSA (1.5 equiv), MeOH, reflux, 20 h, d.r. 17:1, 93% for
1ba; reflux, 4 h, d.r. >20:1, 91% for 11bb; e) TEMPO (0.1 equiv),
BAIB (1.2 equiv), CH Cl , RT, 4 h; 9b (3.0 equiv), NaH (3.0 equiv),
1
2
2
THF, À788C, 4 h, Z/E>20:1, 82% for (Z)-12. BAIB=bis(acetoxy)-
iodobenzene, TEMPO=2,2,6,6-tetramethylpiperidine oxide, pTSA=
para-toluenesulfonic acid, THF=tetrahydrofuran.
Scheme 4. Construction of the cis-THP 11bc and trans-THP 11bd:
a) CSA (2.0 equiv), acetone, reflux, 35 h; 92%; c) TEMPO (0.1 equiv),
BAIB (1.2 equiv), CH Cl , RT, 5 h; 9a (1.5 equiv), RT, 3 h, E/Z>20:1,
2
2
by introducing a Z alkene through a similar procedure with
9
4% for (E)-14; 9b (1.5 equiv), NaH (1.5 equiv), THF, À788C, 1 h,
Z/E 10:1, 87% for (Z)-15; c) pTSA (1.5 equiv), MeOH, reflux, 20 h, d.r.
4:1, 89% for 11bc; reflux, 4 h, d.r. >20:1, 90% for 11bd. CSA=cam-
phorsulfonic acid.
[17]
the Still–Gennari phosphate 9b. The following cyclization
under identical reaction conditions afforded the trans-THP
1
[18]
1
1bb, a C7-epimer of 11ba, in 91% yield.
The high
6
282 www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 6280 –6284

Angewandte
Communications
Chemie
group has the potential to be revealed as a hydroxymethyl
sion (15JC1400400 to R.H.) is highly appreciated. S.-H.H. also
[
8]
group at a late stage of the synthesis of 1. This practical
synthesis sequence was further exemplified in the cyclization
of 15, which readily arose from 13 by oxidation/Horner–
Wadsworth–Emmons (HWE) olefination. The synthesis route
illustrated here offers a complete platform to access four
diastereomers of the hydropyran derived from anti,anti-4b
thanks Shanghai Institute of Technology (XTCX2015-16) for
support. We thank Jie Sun (SIOC) for the X-ray analysis and
Wenhua Li for helpful discussions.
Keywords: allenes · boranes · heterocycles ·
homoallylic alcohols · Michael addition
(
see Figure S1).
How to cite: Angew. Chem. Int. Ed. 2016, 55, 6280–6284
Angew. Chem. 2016, 128, 6388–6392
With successful access to the stereovariants of THP from
b, we decided to complete the stereoisomer derived from
4
anti,syn-4c by this deprotection/chain elongation/cyclization
strategy (Scheme 5). After removal of the benzyl group, the
[
1] Pederin: a) F. Z. Netolitzky, Z. Angew. Entomol. 1919, 5, 252;
b) A. Furusaki, T. Watanabe, T. Matsumoto, M. Yanagiya,
Tetrahedron Lett. 1968, 9, 6301; Ambruticin S: c) D. T. Connor,
R. C. Greenough, M. von Strandtmann, J. Org. Chem. 1977, 42,
3
664; Lasonolide A: d) P. A. Horton, F. E. Koehn, R. E. Long-
ley, O. J. McConnell, J. Am. Chem. Soc. 1994, 116, 6015.
2] a) J. Piel, Proc. Natl. Acad. Sci. USA 2002, 99, 14002; b) B. Julien,
Z.-Q. Tian, R. Reid, C. D. Reeves, Chem. Biol. 2006, 13, 1277;
c) S. Sudek, N. B. Lopanik, L. E. Waggoner, M. Hildebrand, C.
Anderson, H. Liu, A. Patel, D. H. Sherman, M. G. Haygood, J.
Nat. Prod. 2007, 70, 67; d) H. Irschik, M. Kopp, K. J. Weissman,
K. Buntin, J. Piel, R. Müller, ChemBioChem 2010, 11, 1840; e) P.
Pçplau, S. Frank, B. I. Morinaka, J. Piel, Angew. Chem. Int. Ed.
2013, 52, 13215; Angew. Chem. 2013, 125, 13457; f) G. Berkhan,
F. Hahn, Angew. Chem. Int. Ed. 2014, 53, 14240; Angew. Chem.
2014, 126, 14464.
[
Scheme 5. Three-step synthesis of The cis-THP 11ca from anti,syn-4c:
a) lithium (12.0 equiv), naphthalene (16.0 equiv), THF, À788C, 4 h,
9
0%; b) TEMPO (0.1 equiv), BAIB (1.3 equiv), CH Cl , RT; 9a
2 2
(1.5 equiv), RT, E/Z>20:1, 91%; c) pTSA (1.5 equiv), MeOH, reflux,
[3] H. Luhavaya, M. V. B. Dias, S. R. Williams, H. Hong, L. G.
de Oliveira, P. F. Leadlay, Angew. Chem. Int. Ed. 2015, 54, 13622;
Angew. Chem. 2015, 127, 13826.
2
0 h, d.r. >20:1, 93%.
[
4] a) T. L. B. Boivin, Tetrahedron 1987, 43, 3309; b) P. A. Clarke, S.
Santos, Eur. J. Org. Chem. 2006, 2045; c) I. Larrosa, P. Romea, F.
Urpí, Tetrahedron 2008, 64, 2683; d) N. M. Nasir, K. Ermanis,
P. A. Clarke, Org. Biomol. Chem. 2014, 12, 3323; e) M. A. Perry,
S. D. Rychnovsky, N. Sizemore, Top. Hetereocycl. Chem., Vol. 35
selective oxidation of the resulting primary alcohol under-
went a clean conversion and the following Wittig olefination
proceeded smoothly to give the E-alkene 17 in 91% yield.
The cis-THP 11ca was isolated in excellent yield with a ratio
of over 20:1 under acidic conditions. The total synthesis
comprises four steps with 53% overall yield from (R)-6.
In summary, we have disclosed a mechanism-based
hydroboration of allenes and subsequent allylation to
enable the stereoselective synthesis of syn,syn-, anti,anti-
and anti,syn-1,3-diols, which were further used in an oxa-
(Ed.: J. Cossy), Springer, Heidelberg, 2014, pp. 43 – 96; for
a particularly interesting approach with Prins cyclization, see:
f) E. A. Crane, K. A. Scheidt, Angew. Chem. Int. Ed. 2010, 49,
8
316; Angew. Chem. 2010, 122, 8494; g) X. Han, G. R. Peh, P. E.
Floreancig, Eur. J. Org. Chem. 2013, 1193.
[
5] a) E. Lee, Y. H. Song, J. W. Kang, D.-S. Kim, C.-K. Jung, J. M.
Joo, J. Am. Chem. Soc. 2002, 124, 384; b) H. Y. Song, J. M. Joo,
J. W. Kim, D.-S. Kang, C.-K. Jung, H. S. Kwak, J. H. Park, E. Lee,
C. Y. Hong, S. W. Jeong, K. Jeon, J. H. Park, J. Org. Chem. 2003,
[19]
Michael cyclization for the stereodivergent synthesis
of
functionalized THPs. The unprecedented monoalkyl allylbor-
ane in the hydroboration of allenes and subsequent allyllation
implies a novel stereocontrol mechanism which deserves
additional detailed investigation. With the established kinetic
or thermodynamic hydroboration of allenes, this tactic
formed all stereoisomers of the hydropyrans (16 isomers in
principle) in just four steps with overall yields of 53 ~ 69%
from the given chiral allenic alcohol. The practicality of
individual transformations as well as the orthogonal reactiv-
ities of versatile functional groups provides a route to
establish stereocongeners of THPs within biologically impor-
tant polyketides for prospective SAR studies.
6
8, 8080; c) S. H. Kang, S. Y. Kang, C. M. Kim, H.-w. Choi, H. S.
Jun, B. M. Lee, C. M. Park, J. W. Jeong, Angew. Chem. Int. Ed.
003, 42, 4779; Angew. Chem. 2003, 115, 4927; d) T. Yoshimura,
2
F. Yakushiji, S. Kondo, X. Wu, M. Shindo, K. Shishido, Org. Lett.
2006, 8, 475; e) A. K. Ghosh, G. Gong, Org. Lett. 2007, 9, 1437;
f) A. K. Ghosh, G. Gong, Chem. Asian J. 2008, 3, 1811; g) B. M.
Trost, C. E. Stivala, K. L. Hull, A. Huang, D. R. Fandrick, J. Am.
Chem. Soc. 2014, 136, 88 and other synthetic efforts cited
therein.
[
6] a) H. Fuwa, K. Noto, M. Sasaki, Org. Lett. 2011, 13, 1820; b) H.
Fuwa, Heterocycles 2012, 85, 1255; c) C. F. Nising, S. Bräse,
Chem. Soc. Rev. 2012, 41, 988.
[7] L. Yang, G. He, R. Yin, L. Zhu, X. Wang, R. Hong, Angew.
Chem. Int. Ed. 2014, 53, 11600; Angew. Chem. 2014, 126, 11784.
[
[
8] See the Supporting Information for details.
9] C. Sµnchez, X. Ariza, J. Cornellà, J. Farràs, J. Garcia, J. Ortiz,
Chem. Eur. J. 2010, 16, 11535.
Acknowledgments
[
10] a) K. K. Wang, Y. G. Gu, C. Liu, J. Am. Chem. Soc. 1990, 112,
424; b) Y. G. Gu, K. K. Wang, Tetrahedron Lett. 1991, 32, 3029.
11] H. C. Brown, A. K. Mandal, N. M. Yoon, B. Singaram, J. R.
Financial support from the National Natural Science Foun-
dation of China (21290184, 21472223 to R.H. and 21402121 to
S.H.H.) and the Shanghai Science and Technology Commis-
4
[
Schwier, P. K. Jadhav, J. Org. Chem. 1982, 47, 5069.
Angew. Chem. Int. Ed. 2016, 55, 6280 –6284
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
6283

Angewandte
Communications
Chemie
[
[
12] W. Li, Z. Lin, L. Chen, X. Tian, Y. Wang, S.-H. Huang, R. Hong,
[19] Recent elegant demonstration on stereodivergent synthesis:
a) M. A. Schafroth, G. Zuccarello, S. Krautwald, D. Sarlah, E. M.
Carreira, Angew. Chem. Int. Ed. 2014, 53, 13898; Angew. Chem.
2014, 126, 14118; b) P. B. Brady, S. Oda, H. Yamamoto, Org. Lett.
2014, 16, 3864; c) X.-F. Wei, Y. Shimizu, M. Kanai, ACS Cent.
Sci. 2016, 2, 21; d) A. Millµn, J. R. Smith, J. L.-Y. Chen, V. K.
Aggarwal, Angew. Chem. Int. Ed. 2016, 55, 2498; Angew. Chem.
2016, 128, 2544.
Tetrahedron Lett. 2016, 57, 603.
13] For another pseudo-C -symmetric syn,anti-stereoisomer 4d, see
2
a detailed discussion in Figure S1 in the Supporting Information.
14] H.-J. Liu, J. Yip, K.-S. Shia, Tetrahedron Lett. 1997, 38, 2253.
15] J.-M. Vat›le, Tetrahedron Lett. 2006, 47, 715.
[
[
[
16] CCDC 1061925 (11ba) contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
17] W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405.
18] The monobenzoate derivative of 11bb was crystalline and
suitable for the determination of absolute stereochemistry.
CCDC 1445508 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre.
[
[
Received: January 18, 2016
Revised: February 23, 2016
Published online: April 13, 2016
6
284 www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 6280 –6284