Two Enabling Strategies for the Stereoselective Conversion of Internal Alkynes into Trisubstituted Alkenes

Article abstract of DOI:10.1002/chem.201702470

An expedient method for the C-methylation of alkenylstannanes with formation of trisubstituted alkenes is described, which relies on the use of MeI in combination with copper thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with catalytic amounts of Pd(PPh₃)₄. Under these conditions, the reaction is robust, high yielding, and compatible with many functional groups that might not subsist under more traditional conditions used to C-alkylate organotin derivatives. A qualitative analysis of the reaction profile suggested that the in situ formation of a reactive organocopper intermediate and its interception by MeI is only barely faster than O-methylation of the phosphinate additive by the same alkylating agent. To guarantee high yields and prevent net protodestannation from occurring, the reaction protocol had to be optimized such that these competing processes are properly decoupled. The new method is particularly well suited for the stereoselective preparation of the (E)-2-methylbut-2-en-1-ol motif that is present in numerous natural products. Alternatively, this particular target structure can be accessed starting from α-hydroxy alkenylsiloxane precursors, which get C-methylated upon exposure to CuI/LiOtBu and MeI by what is thought to be a Brook rearrangement/ alkylation sequence. The required substrates are best prepared by ruthenium-catalyzed trans-hydrosilylation or trans-hydrostannation of propargyl alcohols.

Full text of DOI:10.1002/chem.201702470

A Journal of
Accepted Article
Title: Two Enabling Strategies for the Stereoselective Conversion of
Internal Alkynes into Trisubstituted Alkenes
Authors: Alois Fürstner, Nikolas Huwyler, Karin Radkowski, and
Stephan M. Rummelt
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To be cited as: Chem. Eur. J. 10.1002/chem.201702470
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10.1002/chem.201702470
Chemistry - A European Journal
Two Enabling Strategies for the Stereoselective Conversion of Internal Alkynes into Trisubstituted
Alkenes
Nikolas Huwyler, Karin Radkowski, Stephan M. Rummelt, and Alois Fürstner*
Dedicated to Professor Teruaki Mukaiyama in celebration of his 90th birthday (Sotsuju)
Abstract: An expedient method for the C-methylation of alkenylstannanes with formation of
trisubstituted alkenes is described, which relies on the use of MeI in combination with copper
thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an
effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with
catalytic amounts of Pd(PPh3)4. Under these conditions, the reaction is robust, high yielding and
compatible with many functional groups that might not subsist under more traditional conditions
used to C-alkylate organotin derivatives. A qualitative analysis of the reaction profile suggested that
the in situ formation of a reactive organocopper intermediate and its interception by MeI is only
barely faster than O-methylation of the phosphinate additive by the same alkylating agent. To
guarantee high yields and prevent net protodestannation from occuring, the reaction protocol had to
be optimized such that these competing processes are properly decoupled. The new method is
particularly well suited for the stereoselective preparation of the (E)-2-methylbut-2-en-1-ol motif
that is present in numerous natural products. Alternatively, this particular target structure can be
accessed starting from -hydroxy alkenylsiloxane precursors, which get C-methylated upon exposure
to CuI/LiOtBu and MeI by what is thought to be a Brook rearrangement / alkylation sequence. The
required substrates are best prepared by ruthenium catalyzed trans-hydrosilylation or trans-
hydrostannation of propargyl alcohols.
*
Dr. N. Huwyler, K. Radkowski, Dr. S. M. Rummelt, Prof. A. Fürstner
Max-Planck-Institut für Kohlenforschung
45470 Mülheim/Ruhr (Germany)
E-mail: fuerstner@kofo.mpg.de
Supporting Information for this article can be found on the WWW under #################
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Introduction
The conversion of internal alkynes in general and propargyl alcohol derivatives A in particular into
trisubstituted alkenes D often proceeds via regioselective hydrostannation with formation of
compounds of type B (E = Sn), followed by tin/halogen exchange and coupling of the resulting alkenyl
halide C with an appropriate methyl donor (Me2Zn, Me4Sn, Me3Al, Me2CuLi etc.) (Scheme 1).1,2 While
this sequence was proven robust and has therefore served natural product total synthesis well, the
tin/halogen exchange can actually be skipped by engaging the alkenylstannane intermediates B (E =
Sn) directly into alkylation. This has been achieved by tin/lithium exchange under cryogenic
conditions and quenching of the resulting organolithium intermediates with MeX;3 alternatively, the
combination of a dimethylcyanocuprate reagent and MeI was found effective.4 Neither of these
methods, however, seemed appropriate for a late-stage application to the total synthesis of the
antibiotic 5,6-dihydrocineromycin B (2):5 formation of an organolithium intermediate is obviously
precluded by the presence of the lactone carbonyl and the two protic sites in stannane 1, whereas
the use of a cyanocuprate reagent would jeopardize the enoate subunit. Therefore we were
prompted to develop an alternative procedure with better functional group compatibility.
Scheme 1. Conversion of propargyl alcohols into products comprising a (E)-2-methylbut-2-en-1-ol
subunit; application to the total synthesis of dihydrocineromycin B; CuTC = copper thiophene-2-
carboxylate
2
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Chart 1. Selected natural products comprising one or more E-configured 2-methyl-but-2-en-1-ol
subunits (or a simple derivative thereof)
In view of the tremendous progress made in recent years in the use of alkyl halides as electrophilic
partners for cross coupling in general,6 a Stille/Migita reaction between 1 and MeI seemed to
represent an attractive solution.7 While a number of higher alkyl halides have in fact been
successfully reacted with various organotin reagents under palladium catalysis,8 the use of MeI had
hardly any precedent prior to our work. A notable exception was an investigation into PET-imaging
(position emission tomography), in which 11CH3I had been treated with a large excess of an
alkenylstannane partner to afford the desired isotopically labeled product;9 such stoichiometry,
however, is clearly inappropriate for target-oriented synthesis. It was therefore gratifying to find that
3
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a procedure previously developed in our laboratory for demanding Stille/Migita reactions could be
adapted to the projected case:10 thus, rapid sequential addition of CuTC (1.05 equiv.) and MeI (1.5
equiv.) to a stirred solution of the functionalized stannane 1, [Pd(PPh3)4] (5 mol%) and [Ph2PO2][NBu4]
(1.1 equiv.) in DMF furnished the desired natural product 2 in 92% yield (286 mg scale) as the final
step of the total synthesis of this antibiotic.5
Because this method – in contrast to many other modern Stille/Migita protocols7,11  is fluoride free,
does not require strong donor ligands and proceeds under virtually neutral conditions, it holds the
promise of ensuring an excellent tolerance towards sensitive functional groups. Therefore it seemed
worthwhile to investigate its scope and limitations in detail. This is all the more true since the (E)-2-
methylbut-2-en-1-ol motif is a very common substructure in natural products; some representative
examples are compiled in Chart 1. Moreover, recent progress in metal catalyzed trans-
hydrometalation of alkynes makes the required organotin precursors of type B (E = Sn) readily
available in isomerically pure form;12,13,14 the analogous alkenylsilanes B (E = Si) are equally well
accessible and hence also deserve consideration as possible substrates.12,15,16 Outlined below is a
summary of our investigations in this field, which now allow us to engage either type of precursor
into productive and selective methylation reactions. Interestingly though, we learned that what
seemed to be a regular Stille/Migita cross coupling at the outset of our study is most likely a purely
copper mediated process, in which the added palladium catalyst serves as an adjuvant rather than an
indispensable catalyst in many cases.
Results and Discussion
Copper-Mediated Methylation of -Hydroxy Alkenylstannanes. As mentioned above, the
methylation reaction used for the total synthesis of 5,6-dihydrocineromycin B (2)5 resorted to a
protocol previously developed in our laboratory for exigent Stille/Migita reactions.10 It is based on
the use of catalytic [Pd(PPh3)4] (or another appropriate palladium catalyst) in combination with CuTC
and [Ph2PO2][NBu4] in DMF as the preferred solvent; while the application of each of these
components has had precedent in the literature,17,18 we noticed that the combination of the three
allows an important synergistic effect to be harnessed. It is believed that CuTC engenders
transmetalation of the organotin precursor with formation of a reactive organocopper species,
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whereas the added phosphinate serves as essentially neutral tin scavenger that renders the
transmetalation irreversible and facilitates the isolation of the product, while not doing any harm
even to highly decorated and labile partners. In this regard [Ph2PO2][NBu4] is superior to fluoride
additives commonly used as tin scavengers otherwise,7,11 which endanger base-labile functionality
and, in particular, silyl protecting groups that are ubiquitous in target oriented synthesis.19,20
Table 1. Optimization of the copper-mediated, palladium-assisted methylation of alkenylstannanes.
Entry CuTC [equiv.]
[Ph2PO2][NBu4] [equiv.] Pd(PPh3)4 [mol%] MeI [equiv.]
3:4:5[b]
1
2
3
4
5
---
1.5
1.05
1.05
1.5
1.5
---
1.1
1.1
1.5
5
5
---
5
5
5
5
100:0:0
0:58:42
17:69:14
2:98:0 (90%)[c]
40:57:3
1.5[a]
1.5[a]
5
[b]
1
[c]
[a] MeI was added quickly ( 30 sec) after the addition of CuTC; ratio as determined by H NMR; isolated
yield of pure product
Prior to the actual application of this methodology to the unprecedented methylation reaction en
route to 5,6-dihydrocineromycin B (2),5 a brief optimization had been undertaken using stannane 3
as the model compound (Table 1). While this study ultimately furnished the desired product 4 in
excellent yield and purity (entry 4), an unexpected correlation of the outcome with the order and
rate of addition of the different components to the reaction mixture was observed; these parameters
had not been critical in any of the previous applications of the methodology to regular sp2-sp2
Stille/Migita coupling reactions.10,19,20 Best results were obtained when CuTC (1.05 equiv.) was added
to a stirred solution of 3, [Pd(PPh3)4] (5 mol%) and [Ph2PO2][NBu4] (1.1 equiv.) in DMF; the addition of
MeI (1.5 equiv.) had to follow quickly to avoid substantial protodestannation from occurring, with a
lag time of no more than 30 seconds being optimal. The order of addition of MeI and CuTC can be
reversed; even though the interval once again proved relevant, it was found that the protocol
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became somewhat more forgiving with respect to the acceptable lagtime (method A). Somewhat
surprisingly at first sight, all attempts to drive the conversion and minimize protodestannation by
increasing the amount of MeI from 1.5 to 5 equivalents proved counterproductive, as the conversion
invariably stalled (entry 5). These observations must have mechanistic implications (see below).
Additional conclusions were drawn from a series of control experiments. Most notably, it was found
that the palladium complex alone was incapable of inducing any cross coupling (entry 1), whereas
the use of CuTC in the absence of [Pd] led to appreciable conversion (entry 3). Therefore the
methylation reaction does not seem to be an ordinary Stille/Migita process involving a
methylpalladium intermediate as the electrophilic partner; rather, it is more likely to proceed by
direct alkylation of an organocopper species with MeI.21 Yet, the comparison of entries 3 and 4
indicates that added [Pd(PPh3)4] exerts a positive influence on the product distribution under the
chosen conditions. The exact role of this palladium adjuvant apart, the examples compiled in Table 3
prove that method A is broadly applicable and ensures efficient methylation of a variety of
functionalized alkenylstannanes.
This favorable application profile notwithstanding, we conjectured that further optimization of the
conditions might allow an entirely palladium-free protocol to be established too. One might envisage
that [Pd(PPh3)4] merely serves as source of PPh3, which stabilizes and/or activates the organocopper
intermediate transiently formed. To test this hypothesis, various phosphines or Ph3As were added to
the mixture, which indeed affected the conversion as well as the product ratio.22 In preparative
terms, however, [Pd(PPh3)4] proved superior (Table 2, compare entry 4 with entries 5-10), perhaps
for its ability to act as a reservoir that “buffers” the concentration of free phosphine in solution,
which might inhibit conversion if present in higher concentration.
Screening of alternative copper sources did not provide a hit either (entries 1, 2). Gratifyingly though,
the solvent was identified as a critical parameter: whereas THF and MeCN performed poorly (entries
11, 12), replacement of DMF by DMSO suppressed the competing protodestannation almost
completely. Under the optimized conditions (entry 14, method B), the desired trisubstituted alkene 7
was obtained in isomerically pure form in 85% yield (>95%, NMR), with only traces of the
protodestannated product 8 being detected in the crude material.23
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Table 2. Optimization of a “copper-only” method for the methylation of alkenylstannanes.[a]
Entry CuX
[equiv.]
[Ph2PO2][NBu4]
[equiv.]
Additive
[mol%]
Solvent
t (h)
Conversion[b]
7:8 [b]
1
2
3
4
5
6
7
8
CuOAc (1.2)
CuO2PPh2 (1.2)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
CuTC (1.05)
1.1
---
---
---
---
DMF
DMF
DMF
DMF
DMF
DMF
DMF
18
<10%
>95%
>95%
>95% (85%)[c]
90%
50%
66%
80%
85%
95%
75%
>95%
>95%
>95% (85%)[c]
n.d.
7:93
71:29
97:3
2.5
2.5
0.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
[(Ph3P)4Pd] (5)
Ph3P (10)
Ph3P (50)
(2-furyl)3P (50)
(p-FC6H4)3P (50) DMF
(F5C6)3P (50)
84:16
88:12
89:11
90:10
32:68
82:18
72:28
42:58
90:10
99:1[d]
9
DMF
DMF
THF
MeCN
DMSO
DMSO
10
11
12
13
14
Ph3As (50)
---
---
---
---
[a]
[b]
Unless stated otherwise, all reactions were carried out at RT using 1.5 equivalents of MeI; amount of
1
[c]
product (relative to substrate) in the crude material, as determined by H NMR; isolated yield of pure
product; [d] 3 equivalents of MeI were used
Table 3. Methylation of alkenylstannanes; for the sake of clarity, only the newly introduced methyl
group is denoted “Me”.
Entry
Product
Method A [a,c]
Method B [b,c]
1
92% (97:3)
85% (99:1)
2
3
4
5
84% (95:5)
88% (94:6)
88% (79:21)
81% (98:2)
81% (99:1)
83% (97:3)
76% (94:6)
85% (98:2)
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6
7
92% (99:1)
86% (99:1)
8
9
82% (99:1)
76% (96:4)
10
72% (95:5)
11
12
79% (90:10)
72% (97:3)
67% (98:2)
13
14
84% (92:8)
84% (94:6)
61% (94:6)
15
16
[d]
17
66% (98:2)
18
19
56% (99:1)
75% (99:1)
[d]
[d]
[a] Method A: Pd(PPh3)4 (5 mol%), [Ph2PO2][NBu4] (1.1 equiv.), MeI (1.5 equiv.), CuTC (1.05 equiv, added 30 sec.
after the addition of MeI), DMF (0.2 M), RT; [b] Method B: [Ph2PO2][NBu4] (1.1 equiv.), MeI (3 equiv.), CuTC (1.05
equiv., added within 30 sec after the addition of MeI), DMSO (0.2 M), RT; [c] yield of the isolated product (ratio
of methylated to protodestannylated compound, as determined by NMR); [d]  50% conversion, as determined
by 1H NMR
This procedure also allowed a host of compounds of type B (E = Sn) to be methylated in good to
excellent yields, no matter whether the free –OH groups adjacent to the tin moiety were primary,
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secondary or tertiary (Table 3); conceivable O-methylation has not been observed in any of these
cases. Even fragile doubly allylic alcohol groups proved stable (entries 3, 10), which attests to the
mildness of the method. Several other functional groups remained equally untouched, including
aldehydes, ketones, esters, enoates, nitriles, amides and phthalimides.24 The copper-only variant
(method B) allows even alkyl-, aryl- and alkenyl halides to be present in the substrate, which are
endangered in the palladium-assisted manifold (entries 12, 13).
Interestingly though, method B is essentially restricted to substrates comprising an unprotected
hydroxy group at the allylic position flanking the tin moiety. Even alkenylstannanes with an –OH
substituent at the homoallylic site were found to react much slower; gratifyingly though, method A is
applicable in such cases (entries 14-19).
Mechanistic Rationale. Tin/copper transmetalation is believed to be reversible in polar
solvents.17,22b,25,26 It is at this stage that the phosphinate exerts its essential function in that it
scavenges the tin residue in form of the only sparingly soluble stannylester H,18 which in turn drives
the conversion (Scheme 2). The resulting alkenylcopper species E reacts with MeI presumably via a
standard CuI/CuIII manifold (intermediate G)21 to give the desired product D.
Scheme 2. Proposed mechanistic scenario
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The key organocopper intermediate E, however, is not the only nucleophile in solution. O-
Methylation of [Ph2PO2] (and/or thiophene-2-carboxylate) with formation of the methyl ester I
(and/or K) might compete with the desired transformation. A control experiment showed this to be
likely, since t1/2 for the reaction of [Ph2PO2][NBu4] with MeI in DMF was found to be  90 min and
hence on the same timescale as productive C-methylation; in fact, variable amounts of I were
detected in the crude materials.27 This competing process, however, is detrimental as it depletes the
mixture in promotor and alkylating agent alike and hence eventually brings the desired reaction to a
halt. Based on this analysis it is clear why the use of a larger excess of MeI had not proven
advantageous but caused incomplete conversion (see Table 1, entry 5). Moreover, if formation of the
alkenylcopper species E continues after the alkylating agent has been consumed by this competing
process, protodestannation with formation of M is the necessary consequence.28
This qualitative picture explains why tin/copper exchange and interception of the resulting reactive
intermediate must be decoupled or, at least, well synchronized. It also suggests that the alkylating
ability of the electrophile has to be carefully considered. Although it may seem counterintuitive,
replacement of MeI by more powerful reagents such as ROTf, BnOCH2Cl or allyl bromide was
detrimental rather than advantageous.29 These electrophiles react preferentially with the
phosphinate and hence fail to afford preparatively meaningful levels of C-alkylation.
Since CuTC was by far the best of all copper salts investigated, it is reasonable to assume that the
thiophene-2-carboxylate ligand is more than a bystander but plays an active role in the overall
process.30 By virtue of its particular geometry and chelate character, it likely assists the carbophilic
CuI center in its approach to the -bond of the organotin derivative. Moreover, the carboxylate unit
can enter the ligand sphere of tin during the crucial transmetalation step; in doing so, the
nucleophilicity of the alkenyl residue is transiently increased and the barrier for transmetalation
lowered. Furthermore, it is tempting to speculate that the carbonyl group serves as hydrogen bond
acceptor for the adjacent –OH group, as tentatively sketched in the conceived transition state N;
under this premise, one could easily rationalize why compounds of type B react so well, especially
under the palladium-free conditions, but lose their privileged status upon O-protection or increasing
the distance between oxygen and tin. We emphasize, however, that this latter aspect is highly
speculative as it disregards the excellent hydrogen bond acceptor qualities of DMSO which might
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prevent even such an entropically favored intramolecular array from being transiently formed.31
Ongoing investigations will try to clarify this point.32
C-Methylation of -Hydroxy Alkenylsilanes of Type B (E = Si). Cooperativity between the protic
functionality in the substrate and a chloride ligand in a ruthenium catalyst has recently been shown
to be strong enough to overturn the inherent bias of ruthenium catalyzed trans-hydrosilylations of
propargyl alcohols for silyl delivery distal to the –OH group:15,33 rather, hydrosilylations of propargyl
alcohols A catalyzed by [Cp*RuCl]4 afford products of type B in which the silyl group resides proximal
to the steering substituent in good yields and selectivities (Scheme 3).12,13,16 Since the reaction also
tolerates many functional groups, such compounds deserve consideration as readily accessible and
more benign substrates for C-alkylation.
Scheme 3. Hydroxy-directed hydrosilylation of propargyl alcohols followed by C-alkylation via Brook
rearrangement
Attempted C-methylation under the conditions outlined above (method A or B), however, was to no
avail, likely because silicon/copper transmetalation is either very inefficient or not proceeding at all.
In an attempt to bolster this step, inspiration was drawn from a publication by Takeda and
coworkers.34 These authors had shown that silanes B react with allyl halides in the presence of
CuI/LiOtBu to give the C-allylated silylether derivatives Q (R3 = allyl) in moderate to good yields
(Scheme 3). The reaction is believed to proceed via Brook rearrangement followed by trapping of the
resulting organocopper intermediate P with the activated electrophile. With regard to the substrate
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scope, however, only compounds B with a terminal double bond (R1 = H) could be engaged into
productive C-C-bond formation, and the use of triphenyl(alkenyl)silanes (X = Ph) was imperative.34,35
Table 4. Substrate screening for the C-methylation of alkoxysilanes of type B
Entry
Substrate
R1
R2
R3
Yield (%)
1
2
3
4
9a
9b
9c
9d
Et
Et
Et
< 5
88
91
69
EtO
EtO
EtO
Me
EtO
EtO
Me
Me
EtO
We conjectured that the mandatory use of triphenylsilanes likely reflects the need to lower the
energy of the CSi antibonding orbital as a prelude for successful attack of the adjacent alkoxide onto
the silicon atom that triggers the critical Brook rearrangement;36,37 this step is arguably challenging as
it passes through a four-membered intermediate O. Under the premise that orbital energy lowering
is the key to success, however, silanes of type B carrying electronegative heteroatoms at silicon
should also qualify as substrates.38 Alkoxysilanes B (X = OR), which are easy to make via the
ruthenium catalyzed trans-hydrosilylation referred to above,12,13 fall into this category and were
therefore deemed a potentially very attractive and versatile class of starting materials.
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Table 5. Trisubstituted alkenes prepared by the method shown in Table 4.[a]
[a]
All reactions were performed with CuI (3 equiv.), LiOtBu (3 equiv.), MeI (3 equiv.) in DMF/2-
methyltetrahydrofuran at 0°C to RT
This consideration was rapidly proven correct (Table 4). In fact, a single alkoxide substituent on
silicon proved sufficient for C-alkylation to take place of treatment of compound 9 with LiOtBu, CuI in
DMF/2-methyl-THF as the preferred reaction medium,39 followed by rapid addition of MeI.
Substrates 9b-d with one, two or three RO-groups gave similar yields, with compound 9c being
optimal in terms of reactivity and handling.40 The reaction works not only with MeI but also with
activated electrophiles such as methallyl chloride, as demonstrated by the representative examples
compiled in Table 5. Although the crude products were usually clean, small amounts of the
corresponding allenes R were detected in certain cases, most likely by -siloxide elimination of the
transient organocopper species P.41 This opens an additional prospect for reaction development
which is subject to ongoing investigations in this laboratory.
Conclusions
Recent progress in ruthenium catalyzed alkyne trans-hydrometalation has largely improved the
accessibility of alkenylstannanes and alkenylsilanes in recent years. This is particularly true for
products derived from propargyl alcohol derivatives, which react in a hydroxy-directed manner with
notably high levels of regio- and stereoselectivity. The resulting products of type B provide ample
opportunity for downstream functionalization:42 The copper mediated C-alkylation reactions
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described above further complement the portfolio in that they open a reliable, functional group
tolerant and hence potentially broadly applicable entry into stereochemically well-defined
trisubstituted alkenes; most notably, the (E)-2-methylbut-2-en-1-ol motif is well within reach, which
is a prevalent in innumerous bioactive natural products. It is therefore expected that this new
methodology will serve advanced organic synthesis well. A recent total synthesis of the macrolide
antibiotic 5,6-dihydrocineromycin B (2) has already witnessed this notion, and further applications
meant to strengthen the argument are underway in this laboratory.
Experimental Part
All experimental details can be found in the Supporting Information. The material includes
compound characterization data and copies of spectra of new compounds.
Acknowledgements
Generous financial support by the MPG is gratefully acknowledged. We thank the analytical
departments of our Institute for expert support of our program.
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For the Table of Contents
Your choice: A sequence of ruthenium catalyzed trans-hydrometalation followed by copper
mediated C-alkylation of the resulting alkenylsilane or stannane products opens a concise entry into
trisubstituted alkenes; most notably, the 2-methylbut-2-en-1-ol motif present in countless natural
products is well accessible. The key reactive intermediates are formed in situ either by Brook
rearrangement or by phosphinate-assisted transmetalation.
Keywords: Alkenes  Alkynes  Copper  Hydrometalation  Ruthenium  Silicon  Tin
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The reaction proved robust on various scales; only when working with tiny amounts of
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28
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