Au-Catalyzed [2 + 3] Annulation of Enamides with Propargyl Esters: Total Synthesis of Cephalotaxine and Cephalezomine H

Article abstract of DOI:10.1021/acs.orglett.7b01202

A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl esters has been developed, providing a new method for expeditious assembly of synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based on this key annulation, strategic installation of the pivotal azaspirocyclic core, followed by constructing the benzazepine unit via Witkop cyclization, led to the divergent total syntheses of cephalotaxine and cephalezomine H.

Full text of DOI:10.1021/acs.orglett.7b01202

Letter
pubs.acs.org/OrgLett
Au-Catalyzed [2 + 3] Annulation of Enamides with Propargyl Esters:
Total Synthesis of Cephalotaxine and Cephalezomine H
Xiao-Yan Ma,† Xian-Tao An,† Xian-He Zhao,† Ji-Yuan Du,†,§ Yu-Hua Deng,† Xiang-Zhi Zhang,†
and Chun-An Fan*,†,‡
†State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, 222
Tianshui Nanlu, Lanzhou 730000, China
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China
§College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China
S
* Supporting Information
ABSTRACT: A novel Au-catalyzed [2 + 3] annulation reaction of
enamides with propargyl esters has been developed, providing a new
method for expeditious assembly of synthetically useful functionalized 1-
azaspiro[4.4]nonane building blocks. Based on this key annulation, strategic
installation of the pivotal azaspirocyclic core, followed by constructing the
benzazepine unit via Witkop cyclization, led to the divergent total syntheses
of cephalotaxine and cephalezomine H.
ephalotaxine possessing an aza-quaternary scaffold (Figure
1) was first isolated from Cephalotaxus drupacea and
C
Cephalotaxus fortunei by Paudler in 1963,1 and its stereochemistry
was entirely established using X-ray analysis by Powell in 1974.2
Generally,cephalotaxinerepresentstheparentpolycycliccoreofa
series of Cephalotaxus alkaloids. Despite the inactivity of
cephalotaxine alone, homoharringtonine as one of its esters has
been approved by the FDA for treatment of chronic myeloid
leukemiasince2012.3 Duetotheintriguingpolycyclicarchitecture
as well as the pharmaceutical potential, Cephalotaxus alkaloids
have attracted significant attention in synthetic community4,5
since the chemical synthesis of cephalotaxine by Weinreb and
Semmelhack in 1972.6
Figure 1. Selected alkaloids containing 1-azaspiro[4.4]nonane unit.
Scheme 1. Au-Catalyzed Annulation Reaction
Structurally, Cephalotaxus alkaloids are characterized with a 1-
azaspiro[4.4]nonane ring system featuring a crucial aza-
quaternary carbon center (Figure 1), which also constitutes an
important architectural subunit in stemonamine-type Stemona
alkaloids.7 Synthetically, a diversity-oriented assembly of such a
functionalizedazaspirocyclicnucleusisofmajorimportanceinthe
expeditious synthesis of related natural products and their
analogues. Focusing on the construction of the 1-azaspiro[4.4]-
nonane ring system driven by the synthesis of cephalotaxine-type
alkaloids, we have recently explored a novel Au-catalyzed [2 + 3]
annulation reaction of enamides with propargyl esters (Scheme
1). To our knowledge, this [2 + 3] annulation has not been
thoroughly explored in the enamide chemistry and the gold-
catalyzed propargyl chemistry.8−12 Herein we wish to present our
preliminary results on this annulation reaction as well as its
applicationinthetotalsynthesisofcephalotaxineanditscongener
cephalezomine H.
azaspiro[4.4]nonane synthon IV could be envisioned to
incorporate the tetracyclic ring system (rings A, B, D, and E)
embedded in our target alkaloids. As for constructing ring C, a
Witkop photocyclization of the synthon III bearing a 4,5-trans
configuration, which would be chemically derived from the
stepwise reduction of IV followed by haloacetamidation, could be
conceived to form the C11−C12 bond in pentacyclic synthon II.
Logically,thelate-stagefunctionalgrouptransformationsdirected
tocephalotaxineandcephalezomineHwouldbeavailablethrough
the common synthon I.
A retrosynthetic analysis of cephalotaxine and cephalezomine
H (Scheme 2) strategically features a design for the assembly of
ring E through a novel catalytic [2 + 3] annulation of enamides V
with propargyl esters VI, wherein the densely functionalized 1-
Received: April 21, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
AgSbF6 was also examined, but the decreased reactivity and
selectivity were observed (24 h, 70% yield, 1:3 dr; entry 7).
Notably, in contrast to the fact that no reaction was observed in a
controlled experiment using the catalyst [IPrAu]+[SbF6]− (entry
8), which was individually prepared from IPrAuCl and AgSbF6,14
this [2 + 3] annulation reaction could proceed with analogous
efficiency (15 min, 86% yield, 1:5 dr; entry 9) after adding AgSbF6
into the above controlled reaction using [IPrAu]+[SbF6]− as a
catalyst (entry 8). It is noteworthy that AgSbF6 itself could not
effectively promote this transformation (entry 10). Importantly,
these facts (entries 8−10) indicate that a positive silver effect is
involved in the current [2 + 3] annulation reaction.15
Scheme 2. Retrosynthetic Analysis
With the optimized reaction conditions in hand, the generality
of this annulation was preliminarily explored (Scheme 3). A
a b c d
, , ,
Scheme 3. Reaction Generality
Based on the above synthetic consideration, a model using
enamide 1a and propargyl acetate 2a was initially investigated for
the key catalytic [2 + 3] annulation reaction. Inspired by the
pioneering exploration of propargyl chemistry under gold
catalysis,12 N-heterocyclic carbene (NHC) gold(I) catalyst
combined with a series of silver salts was first examined in our
model. As tabulated in Table 1, IPrAuCl as a weak-acidic catalyst
a
Table 1. Catalyst Optimization for [2 + 3]-Annulation
b
c
entry
catalyst
time (h) yield (%) dr (trans/cis)
1
IPrAuCl
50
NR
82
90
92
NR
d
2
IPrAuCl/AgNTf2
IPrAuCl/AgBF4
IPrAuCl/AgSbF6
IPrAuCl/AgOAc
IPrAuCl/AgOTf
Ph3PAuCl/AgSbF6
[IPrAu]+[SbF6]−
[IPrAu]+[SbF6]−/AgSbF6
AgSbF6
0.25
0.25
0.25
50
1:5
1:5
1:5
3
4
5
6
50
7
24
70
NR
86
d
1:3
1:5
8
8
a
b
For experimental details, see the Supporting Information. Major
9
0.25
50
isomer indicated, and the dr (trans/cis) determined by 1H NMR.
10
c
d
Isolated yield. The relative configuration was determined by X-ray
a
Performed with 1a (0.12 mmol), 2a (0.10 mmol), and the catalyst
analysis.
b
(0.0025 mmol) in CH2Cl2 (1.0 mL) at 25 °C. Isolated yield.
c
d
Determined by 1H NMR. A complex mixture observed on TLC. NR
variety of propargyl esters 2 with a different ester group
(−OC(O)R2) and aryl group (Ar) were first investigated in
combination with enamide 1a as a two-carbon component. For
example, propargyl esters 2a−2d (Ar = Ph, R2 = Me, t-Bu, Ph,
OBn) were subjected to the standard conditions, and desired
products 3aa−3ad could be obtained in moderate to good yields
(52% to 90%) with modest to moderate diastereoselectivities
(1:2.5 to 1:5.6 dr), wherein the negative influence of a bulky (R2 =
t-Bu) or electron-rich (R2 = OBn) ester group on the annulation
reactivity was observed. Besides, propargyl esters 2e−2h (R2 =
Me, Ar = 4-OMe-C6H4, 4-Br-C6H4, 3-Br-C6H4, 3,4-(OCH2O)-
C6H3) bearing different substituents on the phenyl ring were also
examined, affording products 3ae−3ah in 62% to 94% yields with
1:3.7 to 1:5 dr. To probe the influence of N-substituents (R1) in
enamides 1, two substrates 1b (R1 = n-Bu) and 1c (R1 = Ph) were
evaluated for this annulation by using 2e as a three-carbon
component. ComparedwithN-Bnenamide1a(R1 =Bn), N-butyl
enamide 1b (R1 = n-Bu) gave product 3be with similar reactivity
(97% yield) and stereoselectivity (1:5 dr). In contrast to the
= no reaction.
could not promote the title reaction (entry 1), mostly due to the
strongcoordinationofthechlorideionwithgold(I).Interestingly,
it was found that an in situ formed catalytic system resulting from
the combination of IPrAuCl and AgNTf2 (entry 2) could
effectively enable the expected annulation of 1a with 2a in
CH2Cl2 at 25 °C, affording the desired [2 + 3]-annulated product
3aa in 82% yield with 1:5 dr. Stereochemically, the relative
configuration of major isomer cis-3aa was unambiguously
assigned by X-ray crystallographic analysis.13 Compared with
the reaction efficiency using AgBF4 as an additive (90% yield, 1:5
dr; entry 3), the silver salt AgSbF6 combined with IPrAuCl could
give the optimal result inCH2Cl2 (15 min, 92% yield, 1:5 dr; entry
4). Surprisingly, AgOAc (entry 5) or AgOTf (entry 6) as an
additive in this model led to either no reaction or a complex
mixture. In addition to the above carbene-ligated gold(I) catalyst
(IPrAuCl), phosphane gold(I) chloride combined with silver salt
B
DOI: 10.1021/acs.orglett.7b01202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
preferential cis-selectivity observed in 3aa−3ah and 3be,
interestingly, the [2 + 3] annnulation reaction of N-phenyl
enamide 1c (R1 = Ph) with 2e proceeded in an entirely reversed
diastereoselectivity, leading to the formation of the sole product
trans-3ce (>20:1 dr, 92% yield). The stereochemistry of trans-3ce
was clearly determined by X-ray crystallographic analysis.13
Notably, as seen from its X-ray structure, the observed trans-
selectivity is consistent with the fact that the opposite orientation
of the N-phenyl and C1-aryl group in the spirocyclic skeleton of
3ce could minimize the potential steric repulsion.
exploring such target-oriented synthesis (Scheme 5).18 As shown
in Scheme 5, reductive treatment of trans-3eh with BH3·SMe2
Scheme 5. Synthesis of Cephalotaxine and Cephalezomine H
To further investigate the structural effect of substrates without
a gem-dimethyl group and carbamate moiety, the isoindolinone-
containing enamide 1d was then employed (Scheme 3). Upon
treatment of 1d with 2e under the standard conditions, the
product 3de could be afforded readily (92% yield, 8:1 dr), and the
preferential trans-selectivity was assigned by X-ray crystallo-
graphic analysis of separable major isomer trans-3de,13 to some
extentindicating thattheplanarisoindolinyl ringislessbulky than
the exocyclic N-benzyl group. Moreover, two pyrrolidinonyl-
containing enamides 1e (N-benzyl)16 and 1f (N-(4-methox-
yphenyl))16 wereadditionallyusedinthereactionwith2h,andthe
expected products trans-3eh andtrans-3fh, structurally confirmed
by X-ray crystallographic analysis,13 were obtained with high
stereoselectivity(>20:1dr). Whileusing1e16 withpropargylester
2i having a sterically unfavorable ortho-substituted aromatic ring
(Rb = Br), the crystallographically determined trans-3ei could be
yielded with analogous stereoselectivity (>20:1 dr),13 but in a low
yield (31% yield).
gave tertiary amine 4 in 72% yield, and then a subsequent one-pot
N-debenzylation/enol-acetate hydrogenation, followed by acyla-
tion of the resultant secondary amine, delivered the chloroace-
tamide 5 (X = Cl) in 58% yield over two steps. To access the
benzazepine ringsystem, Witkopphotocyclization19 of5(X=Cl)
withahigh-pressuremercuryvaporlampinaqueousMeOHinthe
presence of NaHCO3 was performed to afford the desired
pentacyclic product 6 in 55% yield, and its stereochemistry with
retention of C4−C5 trans-configuration was confirmed by X-ray
crystallographic analysis.13 Particularly noteworthy is that
Pummerer rearrangement of the sulfoxide resulting from the
oxidationof5″(X=SMe),whichwassuccessfullyusedtoformthe
C11−C12 bond of the benzazepine unit by Ikeda,20 was
ineffective in this case. A two-step protocol involving acetate
hydrolysis and xanthate formation gave xanthogenate ester 7 in
86%yield,whichsubsequentlyunderwentChugaeveliminationto
afford olefin 8 in 85% yield. Upon treating 8 with K2OsO4·2H2O
and NMO, cis-dihydroxylation afforded chromatographically
separable diols 9a and 9b in 98% yield, wherein the configuration
of isomer 9b was determined by X-ray crystallographic analysis.13
Swern oxidation of 9a and 9b could deliver α-enolone 10 in 91%
yield.
To gain preliminary insight into the interesting cis- and trans-
selectivity observed in this annulation, possible rationale is
proposed on the basis of a stepwise annulation mechanism
(Scheme 4).17 First, the propargyl esters 2 undergo a 1,2-acyl shift
Scheme 4. Proposed Mechanism for [2 + 3] Annulation
With the common building block 10 in hand, as described in
Scheme 5, regioselective etherification with dimethoxypropane in
the presence of p-TsOH afforded the enol ether 11 with C4−C5
cis-configuration in 70% yield, and subsequent reduction with
alane furnished the synthesis of ( )-cephalotaxine in 87% yield.
Divergently, a diastereoselective KBH4 reduction of the enolone
motif in 10 could deliver β,β-diol 12 in 52% yield, wherein cis-
configuration at C-4 and C-5 was confirmed by its X-ray
structure.13 Following further alane reduction of the amide
moiety, the synthesis of ( )-cephalezomine H was achieved in
68% yield, and its NMR spectroscopic data are identical to those
from a previous synthesis.21
In conclusion, driven by the total synthesis of Cephalotaxus
alkaloids, anovelNHC-Au(I)/Ag(I)-catalyzed [2+3]annulation
of enamides with propargyl esters has been developed, leading to
an effective construction of the crucial aza-quaternary carbon
center embedded in a highly functionalized 1-azaspiro[4.4]-
through TS-A under gold catalysis, leading to the zwitterionic
resonance species B as one of the main resonance contributors.
Following the nucleophilic attack of enamides 1 to the more
electrophilic C3-position of B, two presumable transition states
TS-C and TS-D, which could deliver cis-3 and trans-3,
respectively,mightbeinvolvedinathermodynamicallycontrolled
pathway for five-membered ring spiro-annulation. Notably, the
minimal steric hindrance between the bulky α-[C] or α-[N]
substituent and the C1−Ar group in TS-C or TS-D could mostly
account for the stereopreference at the final iminium cyclization
step, wherein the observed diastereoselectivity (Scheme 3) is
consistent with an approximate order of increasing bulkiness of
the[C]and[N]substituentsonthespirocyclicquaternarycarbon
center.
Having developed this Au-catalyzed method for the con-
struction of azaspirocycles, we then focused our attention toward
C
DOI: 10.1021/acs.orglett.7b01202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(7)ForselectedreviewsonStemonaalkaloids, see:(a)Pilli, R. A.;Rosso,
G.B.;deOliveira,M.C.F.Nat.Prod.Rep.2010,27,1908.(b)Wang,F.-P.;
Chen, Q.-H. Nat. Prod. Commun. 2014, 9, 1809.
nonane system. Based on this key annulation as well as a Witkop
cyclization, total syntheses of ( )-cephalotaxine and ( )-ceph-
alezomine H were accomplished divergently. The present studies
not only chemically enrich the methodology design for
constructing synthetically useful functionalized azaspirocycles in
gold catalysis but also strategically illustrate the potential of
enamide chemistry in the total synthesis of natural products.
(8)Phosphite-gold-catalyzed cyclopropanation of propargylesterswith
vinyl amides having a strong electron-withdrawing N-sulfonyl group has
been pioneeringly studied by Fiksdahl, in which one example of formal [3
+ 2] cycloaddition of monosubstituted vinyl sulfonamide with 1-
phenylpropargyl pivalate was documented. For details, see: Sperger, C.
A.; Tungen, J. E.; Fiksdahl, A. Eur. J. Org. Chem. 2011, 2011, 3719.
(9) For gold-catalyzed [3 + 2] cycloadditions of propargyl acetals,
insteadofpropargylesters, withenolethers, see:(a)Iqbal, N.;Sperger, C.
A.; Fiksdahl, A. Eur. J. Org. Chem. 2013, 2013, 907. (b) Siah, H.-S. M.;
Kaur, M.; Iqbal, N.; Fiksdahl, A. Eur. J. Org. Chem. 2014, 2014, 1727.
(10) For gold-catalyzed cyclopentaannulation of propargyl esters with
ASSOCIATED CONTENT
* Supporting Information
■
S
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.7b01202.
vinyl ethers or aryl olefins, see: (a) Garayalde, D.; Kruger, K.; Nevado, C.
Angew. Chem., Int. Ed. 2011, 50, 911. (b) Conyers, R. C.; Barnes, C. L.;
Gung, B. W. Tetrahedron Lett. 2015, 56, 3318.
̈
Experimental procedures and spectra data (PDF)
X-ray data for cis-3aa (CIF)
X-ray data for trans-3ce (CIF)
X-ray data for trans-3de (CIF)
X-ray data for trans-3eh (CIF)
X-ray data for trans-3ei (CIF)
X-ray data for trans-3fh (CIF)
X-ray data for 6(CIF)
(11) For recent reviews on the enamide chemistry, see: (a) Matsubara,
R.; Kobayashi, S. Acc. Chem. Res. 2008, 41, 292. (b) Carbery, D. R. Org.
Biomol. Chem. 2008, 6, 3455. (c) Lefort, L.;Boogers, J. A. F.; Kuilman, T.;
Vijn, R.J.;Janssen, J.;Straatman, H.;deVries, J. G.;deVries, A.H. M. Org.
ProcessRes. Dev. 2010, 14, 568. (d)Gopalaiah, K.;Kagan, H. B. Chem. Rev.
2011, 111, 4599. (e) Dake, G. R. Synlett 2012, 23, 814. (f) Kuranaga, T.;
Sesoko, Y.; Inoue, M. Nat. Prod. Rep. 2014, 31, 514. (g) Gigant, N.;
Chausset-Boissarie, L.; Gillaizeau, I. Chem. - Eur. J. 2014, 20, 7548.
(h)Bernadat,G.;Masson,G.Synlett2014,25,2842.(i)Liu,X.;Zheng,K.;
Feng, X. Synthesis 2014, 46, 2241. (j) Wang, M.-X. Chem. Commun. 2015,
51, 6039. (k) Courant, T.; Dagousset, G.; Masson, G. Synthesis 2015, 47,
1799.
X-ray data for 9b (CIF)
X-ray data for 12 (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: fanchunan@lzu.edu.cn.
ORCID
(12) For selected reviews on gold-catalyzed propargylic chemistry, see:
(a) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750.
(b) Marco-Contelles, J.; Soriano, E. Chem. - Eur. J. 2007, 13, 1350.
(c) Lopez, F.; Mascarenas, J. L. Beilstein J. Org. Chem. 2011, 7, 1075.
́
̃
Chun-An Fan: 0000-0003-4837-3394
Notes
(d) Shu, X.-Z.; Shu, D.; Schienebeck, C. M.; Tang, W. Chem. Soc. Rev.
2012, 41, 7698. (e) Shiroodi, R. K.; Gevorgyan, V. Chem. Soc. Rev. 2013,
42, 4991. (f) Fensterbank, L.; Malacria, M. Acc. Chem. Res. 2014, 47, 953.
(g) Ayers, B. J.; Chan, P. W. H. Synlett 2015, 26, 1305. (h) Day, D. P.;
Chan, P. W. H. Adv. Synth. Catal. 2016, 358, 1368. (i) Asiri, A. M.;
Hashmi, A. S. K. Chem. Soc. Rev. 2016, 45, 4471.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for financial support from NSFC (21572083,
21322201, 21290180), FRFCU (lzujbky-2015-48, lzujbky-2016-
ct02,lzujbky-2016-ct07),PCSIRT(IRT_15R28),the111Project
of MOE (111-2-17), and Chang Jiang Scholars Program (C.-
A.F.).
(13) CCDC 1523168 (cis-3aa), CCDC 1523169 (trans-3ce), CCDC
1536571 (trans-3de), CCDC 1536570 (trans-3eh), CCDC 1523172
(trans-3ei), CCDC 1523171 (trans-3fh), CCDC 1523173 (6), CCDC
1523174 (9b), and CCDC 1523175 (12) contain the supplementary
crystallographic data (Supporting Information, SI).
(14) [IPrAu]+[SbF6]− was prepared by mixing IPrAuCl and AgSbF6 in
CH2Cl2 after gravity filtration through celite, and its purity without silver
was confirmed by XPS analysis. For details, see the SI.
REFERENCES
■
(1)Paudler, W. W.;Kerley, G. I.;McKay, J. J. Org. Chem. 1963, 28, 2194.
(2) Arora, S. K.; Bates, R. B.; Grady, R. A.; Powell, R. G. J. Org. Chem.
1974, 39, 1269.
(3) Kantarjian, H. M.; O’Brien, S.; Cortes, J. Clin. Lymphoma, Myeloma
Leuk. 2013, 13, 530.
(4)ForarecentleadingreviewonCephalotaxusalkaloids,see:Abdelkafi,
H.; Nay, B. Nat. Prod. Rep. 2012, 29, 845 and references cited therein.
(5)Forsyntheticworkssince2012,see:(a)Zhang,Q.-W.;Xiang,K.;Tu,
Y.-Q.; Zhang, S.-Y.; Zhang, X.-M.; Zhao, Y.-M.; Zhang, T.-C. Chem. -
(15)ForselectedexamplesonsilvereffectinAu-catalyzedreactions,see:
(a) Weber, D.; Gagne, M. R. Org. Lett. 2009, 11, 4962. (b) Patrick, S. R.;
́
Boogaerts, I.I. F.;Gaillard, S.;Slawin, A.M.Z.;Nolan, S.P. BeilsteinJ. Org.
Chem. 2011, 7, 892. (c) Wang, D.; Cai, R.; Sharma, S.; Jirak, J.;
Thummanapelli, S. K.; Akhmedov, N. G.; Zhang, H.; Liu, X.; Petersen, J.
L.; Shi, X. J. Am. Chem. Soc. 2012, 134, 9012.
(16) Partial isomerization of exocyclic double bond in 1e and 1f to
endocyclic occurs under standard conditions, leading to the aza-fused
annulation products 4eh (23% yield), 4ei (28% yield), and 4fh (42%
yield). For details, see the SI.
Asian J. 2012, 7, 894. (b) Gonca̧ lves-Martin, M. G.; Zigmantas, S.;
Renaud,P.Helv.Chim.Acta2012,95,2502.(c)Xiao,K.-J.;Luo,J.-M.;Xia,
X.-E.;Wang,Y.;Huang,P.-Q.Chem.-Eur.J.2013,19,13075.(d)Xing,P.;
Huang, Z.-G.; Jin, Y.; Jiang, B. Synthesis 2013, 45, 596. (e) Zhang, Z.-W.;
Zhang, X.-F.;Feng, J.; Yang, Y.-H.; Wang, C.-C.; Feng, J.-C.; Liu, S. J. Org.
Chem. 2013, 78, 786. (f) Huang, S.-H.; Tian, X.; Mi, X.; Wang, Y.; Hong,
R.TetrahedronLett.2015,56,6656.(g)Liu,H.;Yu,J.;Li,X.;Yan,R.;Xiao,
J.-C.; Hong, R. Org. Lett. 2015, 17, 4444. (h) Marguerit, M.; Little, G.;
Wang, Y.; He, L.; Allwein, S.; Reif, J.; Rossi, J.; Roemmele, R.; Bakale, R.
Eur. J. Org. Chem. 2015, 2015, 8003. (i) Gouthami, P.; Chegondi, R.;
Chandrasekhar, S. Org. Lett. 2016, 18, 2044.
(17)Analternativepathwayinvolving[2+1]cycloaddition,followedby
vinylcyclopropane rearrangement or cyclopropane ring opening/
cyclization, could not be ruled out at this stage.
(18) For reviews on gold catalysis in natural product synthesis, see:
(a) Zhang, Y.; Luo, T.; Yang, Z. Nat. Prod. Rep. 2014, 31, 489.
(b) Pflasterer, D.; Hashmi, A. S. K. Chem. Soc. Rev. 2016, 45, 1331.
̈
(19)Foraleadingreview,see:Gritsch,P.J.;Leitner,C.;Pfaffenbach,M.;
Gaich, T. Angew. Chem., Int. Ed. 2014, 53, 1208.
(20) Ishibashi, H.; Okano, M.; Tamaki, H.; Maruyama, K.; Yakura, T.;
Ikeda, M. J. Chem. Soc., Chem. Commun. 1990, 1436.
(21) Taniguchi, T.; Yokoyama, S.; Ishibashi, H. J. Org. Chem. 2009, 74,
7592.
(6) (a) Auerbach, J.; Weinreb, S. M. J. Am. Chem. Soc. 1972, 94, 7172.
(b) Semmelhack, M. F.; Chong, B. P.; Jones, L. D. J. Am. Chem. Soc. 1972,
94, 8629.
D
DOI: 10.1021/acs.orglett.7b01202
Org. Lett. XXXX, XXX, XXX−XXX