COMPOSES D'AMINOMETHYLTRIORGANOTINE, .alpha.-MONO OU DISUBSTITUES ET METHODE DE PREPARATION

AMINOMETHYLTRIORGANOTIN COMPOUNDS, .alpha.-MONO OR DISUBSTITUTED, AND METHOD OF PREPARATION

Abrégé anglais

A B S T R A C T
The invention concerns a method of preparation
of aminomethyltriorganotin compounds, preferably .alpha.-mono or
disubstituted, the new tin compounds obtained thereby and
an application of said tin compounds to the synthesis of
aminomethylorganometallic compounds and to the regiospeci-
fic preparation of .beta.-aminoalcohols. The intermediate tin
and metallic compounds are new. The method for preparing
the tin compounds comprises reacting an iminium salt with
a corresponding stannylanion, preferably a triorganostannyl-
anion. This method provides best yields and provides regio-
specific .beta.-aminoalcohols useful by having in most cases a
large spectrum of pharmacological activities.

Revendications

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A method of preparation of an
aminomethyltriorganotin compound, .alpha.-mono or
disubstituted, which comprises reacting a compound of
the formula:
<IMG>
with a compound of the formula:
(R)3SnM
to form a compound of the formula:
<IMG>
wherein, in the above formulae,
R1, R2, R3 and R4 are each independently selected
from the group consisting of hydrogen; saturated or
unsaturated aliphatic, alicyclic or heterocyclic
radicals having 1 to 20 carbon atoms; two of the groups
R1 through R4 may together form a cycloalkyl, fused
cycloalkyl, heterocyclic or fused heterocyclic ring
having up to 20 carbon atoms;
R is an alkyl radical having 1 to 20 carbon atoms;
M is selected from the group consisting of lithium,
sodium, potassium or MgX; and
X is halogen.
2. A method as defined in claim 1, wherein R1
through R4 together form a cycloalkyl or heterocyclic
ring having 5 carbon atoms.
19

3. The method according to claim 1, wherein R1,
R2, R3, R4 are each independently selected from the
group consisting of hydrogen, C1-C3 alkyl, aryl and
furyl groups.
4. A method according to claim 3, wherein aryl is
chosen from phenyl and benzyl.
5. The method according to claim 1, wherein two of
the groups R1 through R4 together form a cyclopentane
ring.
6. The method according to claim 1, wherein two of
the groups R1 through R4 together form with the N atom a
saturated heterocyclic ring having 5 carbon atoms.
7. The method according to claim 1, wherein R is
an n-butyl group.
8. The method according to claim 1, wherein X is
selected from the group consisting of chlorine, bromine
and iodine.
9. The method according to claim 3 or 4, wherein
R1, R2, R3, R4 are each independently selected from the
group consisting of methyl, ethyl and isopropyl.
10. The method according to claim 1, 3 or 4,
wherein R1, R2 are hydrogen and R3, R4 are methyl.
11. The method according to claims 1, 3, or 4,
wherein R1 is isopropyl, R2 is hydrogen and R3, R4 are
ethyl.
12. The method according to claims 1, 3 or 6,
wherein R1 is isopropyl, R2 is hydrogen and R3, R4
together form with the N atom said saturated
heterocyclic ring.

13. The method according to claims 1 or 3, wherein
R1 is isopropyl, R2 is hydrogen, R3 is methyl and R4 is
benzyl.
14. The method according to claims 1, 3 or 5,
wherein R1 and R2 together form a cyclopentane ring, R3
is methyl and R4 is benzyl.
15. The method according to claims 1, 3 or 6,
wherein R1 is hydrogen, R2 is phenyl and R3, R4 together
form with the N atom, said heterocyclic saturated ring.
16. The method according to claims 1, 3 or 6,
wherein R1 is furyl, R2 is hydrogen and R3, R4 together
form with the N atom said heterocyclic saturated ring.
17. An aminomethyltriorganotin compound, mono or
disubstituted in position alpha, corresponding to the
general formula:
<IMG>
wherein R is an alkyl radical having 1 to 20 carbon
atoms; R1, R2, R3, R4 are each independently selected
from the group consisting of hydrogen; saturated or
unsaturated aliphatic, alicyclic or heterocyclic
radicals having 1 to 20 carbon atoms with the proviso
that at least one of R1 and R2 is other than hydrogen;
two of the groups R1 through R4 may together form a
cycloalkyl, fused cycloalkyl, heterocyclic or fused
heterocyclic ring including up to 20 carbon atoms.
18. A compound as defined in claim 17, wherein R1
through R4 together form a cycloalkyl or heterocyclic
ring having 5 carbon atoms.
19. A compound according to claim 17, wherein R is
an alkyl radical having 4 carbon atoms; R1, R2, R3, R4
21

are each independently selected from the group
consisting of hydrogen, C1-C3 alkyl, aryl and furyl
groups, with the proviso that at least one of R1 and R2
is other than hydrogen, two of the groups R1 through R4
may together form a cyclopentane ring or with the N
atom, said saturated heterocyclic ring.
20. A compound according to claim 19, wherein aryl
is chosen from phenyl and benzyl.
21. A compound according to claim 19, wherein R is
an n-butyl group; R1, R2, R3, R4 are each independently
selected from the group consisting of hydrogen, methyl,
ethyl, isopropyl, benzyl, phenyl or furyl, with the
proviso that at least one of R1 and R2 is other than
hydrogen; two of the groups R1 and R2 may together form
a cyclopentane ring and R3, R4 may together form with N
a piperidine ring.
22. A compound according to claim 17, 19 or 21,
wherein R is an n-butyl group, R1 is isopropyl, R2 is
hydrogen and R3, R4 are ethyl.
23. A compound according to claim 17, 19 or 21,
wherein R is an n-butyl group, R1 is isopropyl, R2 is
hydrogen and R3, R4 together form with the N atom a
piperidine ring.
24. A compound according to claim 17, 19 or 21
wherein R is an n-butyl group, R1 is isopropyl, R2 is
hydrogen, R3 is methyl and R4 is benzyl.
25. A compound according to claim 17, 19 or 21,
wherein R is an n-butyl group, R1, R2 together form a
cyclopentane ring, R3 is methyl and R4 is benzyl.
26. A compound according to claim 17, 19 or 21,
wherein R is an n-butyl group, R1 is hydrogen, R2 is
phenyl and R3, R4 together form with N a piperidine
22

ring.
27. A compound according to claim 17, 19 or 21,
wherein R is an n-butyl group, R1 is furyl, R2 is
hydrogen and R3, R4 together form with N a piperidine
ring.
28. A composition comprising an
aminomethylorganotin compound as defined in claim 17 and
an organometallic compound of the formula:
R'-Metal
wherein R' is an alkyl radical having 1 to 20
carbon atoms and said metal is selected from the group
consisting of Li+, K+, Na+, Mg2+ and A13+.
29. A composition according to claim 28, wherein
R' is an alkyl radical having 4 carbon atoms and the
metal is Li+.
30. A composition according to claim 29, wherein
R' is an n-butyl group and the metal is Li+.
23

Description

:~2S2~04
The present invention essentially relates to a methodof preparation of aminomethyltriorganotin compounds, pre-
l0 ferably ~-mono or disubstituted; new aminomethyltriorganotin
compounds o~mono or disubstituted; the application of said
aminomethyltriorganotin compounds to the synthesis of
aminomethylorganometallic compounds, preferably ~mono or
disubstituted; new aminomethylorganometallic compounds ~-
mono or disubstituted and the application of said amino-
methyltriorganotin compounds or of said aminomethylorgano-
metallic compounds to the regiospecific preparation off~-
aminoalcohols.
Hitherto only non-substituted aminomethyltrialkyltin
compounds of the formula R3SnCH2N < have been synthesized
and described in R.G. KOSTYANOVSKII, A.K. PROKOF'EV,
Izv. Akad. Nauk. SSSR. Ser. Khim., (1965). 175; E.W. ABEL,
R.J. ROWLEY, J. Organometal. Chem., 97, (1975),159. The
method of preparation involved the use of halogenomethyl-

~L252~
trialkyltins and of secondary amines or salts thereof.This method is considered to be of little interest due to
the difficulty of preparation of the organostannic reac-
tants (see D. SEYFERTH, S.B. ANDREWS, R.L. LAMBERT, J.
Organometal. Chem., 37. (1972), 69; D. SEYFERTH, E.G. ROCHOW,
J. Am. Chem. Soc., 77, (1955),1302).
Another method has been described in the littera-
ture by D.J. PETERSON in "D.J. PETERSON, J. Organometal.
Chem., 21, (1970), P 63; D.J~ PETERSON, J. Am. Chem. Soc.,
lO 93, ~1971), 4027; D.J. PETERSON, J.F. WARD, J. Organometal.
Chem., 66, (1974), 209~ " This method comprises reacting
a tri-n-butyl stannyllithium with e ectrophilic subs-~'rates
consisting essentially of ~-amino thio ethers and only gives
access to aminomethyltributyltin compounds not substituted.
Further, this method is difficult to carry out
and is of little interest since it lacks the presence of a
substituent on the methyl part thereof.
And, it is and becomes of high interest to be-in
a position to synthesize aminomethyltriorganotin compounds
20 which will be mono- or disubstituted in ~ position since
the aminomethyltrialkyltin compounds are important to pre-
pare, through transmetallation with the aid o~ an organo-
metal, preferably an organolithium, the corresponding amino-
methyl organometallic compounds which constitute reactants
of high potentiality in synthesis,practically inaccessible
through other ways (see A. KRIEF, Tetrahedon, 36, (1980), 2531).
The corresponding chemical reaction is the fol~
ing
R3Sn- C -N~ ~ R'Metal-~ R3SnR' ~- Metal - C - N ~
One essential object of the present invention is
therefore to provide a new method of preparation of amino-
methyltriorganotin compounds, preferably ~-mono or disub-
stituted, which is easy to be put into practice and which
needs only readily available reactants, while providing a

~25~1(1 4
high yield in reaction compound.
Another essential object of the present invention
is to provide new aminomethyltriorganotin compounds ~-mono
or disubstituted, in particular as intermediate compounds
for the synthesis of corresponding organometal compounds,
preferably organolithium compounds.
Accordingly, a further object of the present in-
vention is an application of the aminomethyltriorganotin
compounds to the synthesis of a new aminomethylorganometal-
10 lic compound, preferably a-mono or disubstituted. A further
object of the present invention is the provision of new ami-
nomethylorganometallic compounds ~-mono or disubstituted.
Again, a further object of the present invention
is an application of the abovesaid aminomethyltriorganotin
compounds or of said aminomethylorganometallic compounds to
the preparation of regiospecific ~-aminoalcohols which con-
stitute compounds of high potentiality notably in the phar-
maceutical field.
All these objects are achieved by the present
20 invention.
Accordingly, the present invention provides a
method of preparation of aminomethyltriorganotin compounds,
preferably a-mono or disubstituted, characterized in that
it comprises reacting an iminium salt with a corresponding
stannyl anion, preferably a triorganostannyl anion.
According to a specific embodiment of the inven-
tion method, the iminium salt is preferably an iminium ha-
lide, having the followinq chemical formula:
Rl ¢ R3
C ~ N
R~ \ R4
X
~1herein Rl, R2 each independently can
represent hydrogen; Rl, R2, R3, R4 each independently can
represent any organic radical saturated or unsaturated,
aliphatic or alicyclic, preferably having from 1 to

~252~04
20 carbon atoms, more preferably from 1 to 12 carbon atoms
and most preferably from 1 to 8 carbon atoms.~ The prefer-
red organic radicals are an alkyl,cycloalkyl, aryl, phenyl,
benzyl, furyl group and two R groups taken together can
form a ring saturated or even unsaturated;
X is a halogen atom, preferably selected from a
chlorine atom, iodine atom or bromine atom, and most prefe-
rably is a chlorine atom.
The reaction is advantageously performed within a
solvent in particular ethers, hydrocarbons or mixtures of
solvents, but most preferably in ethers. Diethylethers,
tetrahydrofuran, dimethoxyethane and other ethers can be
used but diethylether is the most preferable ether.
According to a preferred emkodiment, the stannyl ~ion is
a triorgano-stannyl anion of formula R3SnM with M representing MgCl,Li,
Na and K and is preferably MgCl; R is any organic radical as in the
case of the imunium salts; R is preferably an alkyl group and most pre-
ferably n-butyl; X is preferably a halogen atom and most preferably a
chlorine ion.
According to specific emkodiments, the iminium salt is
selected from:
CH2 = N Me2 Me ~
Cl ~le N Et2
/-~ Cl
C =Q ~
H ~r or Cl
Me ~ ~ N
Me ~N l
Cl Cl
r~
N~ O~C N
_ ~ Br
I

~ ~2521~
.Summarizing the above, the invention method of preparation
of the aminomethyltriorganotin comçounds, preferably ~-mono or disub~
stituted can ke represented by the following ehemieal reaction:-
1 3 1 3
R\ ~ R R / R
C N 4 + R3SnM Et~2O~ R3Sn C2 \ 4 +
R R R R
MX X
The aminomethyltriorganotin c~n~ounds which are mono or
10 disubstituted in position ~ are new compounds whieh form a part of thepresent invnetion. Those com~cunds are preferably represented ky the
following chemical formula I:
1 3
R / R
R3 Sn - C - N (I)
RZ \ R4
wherein each of the R radieals or substituents is as previously defined
with the proviso that at least one of R , R is other than hydrogen~
The present invention also eoncerns an application of the
20 above define~ aminomethyltriorganotin ecmpcunds, preferably ;G-mono or
disubstituted to the preparation of corresponding o-amino organometal-
lie eompounds by reacting an organometal with said aminomethyltriorga-
notin compeunds according to the following chemical reaction:
R'-Metal + R3Sn - N ~ R3SnR' + Metal - C - N
R2 \ R4 R2 R4
With the R radicals being as previously defined; R' keing
independently as defined for the R radieals, R' keing preferably iden-
30 tical to R; the metal is preferably selected from Li+, K , Na , Mg ,Al ~ ; most preferably the metal is Li .
The present invention also concerns the new amino
methyl orsanometallie compounds ~-mono or disubstituted

~252~34
which are preferably of the following chemical formula II.
R3
Metal - C - N (II)
R2 R4
Wherein each of the R radicals is as previously defined
with the proviso that at least one of Rl,R2 is other than hydrogen, the
metal is as previously defined and is preferably lithium.
It must be noted that in the above set forth chemical
reaction for preparing the new aminomethylorganome ~ lic ca~x~nds,
10 one of the reaction products is constituted by a tin tetra substituted
com~ound which is easily recycled to constitute the starting organo-
metallic reactant for forming the stannylanion.
Further, according to the present invention, the
most prefered stannylanion is constituted by tri-n-butyl-
stannylmagnesiumchloride which is easily obtained as de-
scribed in "J.C. LAHOURNERE, J. VALADE, C.R. Acad. Sci,
Ser. C., 270, (1970), 2080."
Further, the starting iminium reactants are also
easily available and preparable as described in "Iminium
Salts in Organic Chemistry", H. Bohme, H.G. Viehe Eds,
Advances in Organic Chemistry, vol. 9, part.1 and 2, (1976).
The invention new organometallic compounds are
very useful intermediate compounds for the synthesis of a
number of very useful organic compounds.
One of the most preferred applications of ~he
invention aminomethyltin or metallic compounds which are
preferably ~-mono or disubstituted is the regiospecific
synthesis of ~-amino alcohols.
According to this most preferred application,
the method is characterized in that it comprises reacting
at first the previously defined aminomethyltin compound
onto an organometallic compound and reacting the thereby
obtained aminomethylorganometallic compound with a ketone
or an aldehyde of Formula & ~ which both reactions can
be summarized by the following chemical reaction:

~i~5~
~ R3
R~ ~R3 Rs N R4
R3 Sn C--N --~ R6 > ~--Rl
~ herein each of Rs,R6 can ~e hydrogen or one is H and the
other is an organic radical or both R 5 and R 6 are an orga-
nic radical, as defined ~or the other Rlto R 4, the me~ is as
above defined.
It is of prime importance to note that this in-
vention method provid~s regiospecific ~amino alcohols
which are very useful notably since they have in most cases
a large spectrum of pharmacological activities. Some ex-
amples of such compounds synthesized according to the inven-
tion method will be set forth in the following description.
In this respect, it must be outlined that the
hitherto known method for synthesizing ~-amino alcohols
were often based on the addition of an amine onto an epox-
ide according to the following reaction:
R'2NH
Rl--CH--CH--R2 )Rl- CH--,CHR2 + Rl--~--ÇH~R2
~0~ ~H NR'z R'2N ~H
not permitting to control the regioselectivity of the reac-
tion. The amino group is indeed fixed preferentially to
the side the less hindered of the epoxide so that mixtures
of regioisomers are obtained when the hinderings are close
at the location of the two epoxidic carbons.
For this type of reaction including addition of
an amine onto an epoxide, see E.J. COREY, et. al, J. Am.
Chem. Soc., 87, 1 353 (1965) and P.A. CROOKS, R. SZYNDLER,
Chem. and Ind. 1 111, (1973); J.H. POSNER, D.Z. ROGERS,
30 J. Am. Chem. Soc. 99, 8208 (1977); L.E. OUERMAN, L.A.
~LIPPIN, Tetrahedron Letters 22, 195 (1981).
Other methods only reach aminoalcohols of the
type HO-C-CH2NH2 (see the W.E. PARHAM, C.S. ROOSEVELT,
Tetrahedron Letters 923, (1971);R.F. MEYER et. al. J. Med.

52~1~4
Chem. 16, 1 113 (1973~; D.A. EVANS et. al. J. Org. Chem.
39, 914 (1974); T. KAU~N~ H. BERGI E, K~PPELMANN,D. KUHL-
MANN Chem. Ber. 110, 2 659 (1977); or aminoalcohols of the
type R-C-H and the substituents NH2 CH-CH20H (see M.I,.
ANHOURY et.al. J. Chem.Soc. PERKIN ~rans. I, 191, (1974);
and G. BARLUENGA, F. FANANAS, M. YUS J. Org. Chem. 44,
4 798 (1979).
But according to these last methods, there is no
problem of regioselectivity which latter problem is put for-
ward only when it is wished to synthesize ~-aminoalcohols
which are substituted both onto the carbon bearing the
hydroxyl and onto the carbon bearing the nitrogen.
SHARPLESS has tried to solve this problem through
aminohydroxylation of alkenes (SHARPLESS, et. al. J. Am.
Chem. Soc. 97, 2 305 (1975); J. Org. Chem. 41, 177 (1976) ).
SEEBACH has proposed a method reaching amino
alcohols with secondary or primary amine functions through
the denitrosation of hydroxynitrosamines in D. SEEBAC~ and
D. ENDERS, Angew~ ChemO Int. Ed; 14, 15 (1975).
This way is dangerous in that the nitrosamines
used have cancerigenic properties and this needs a one pot
reaction in view of lowering the risks of contamination.
In view of the above, it is clear that the present
invention provides a new and unobvious way of preparing
regiospecific ~-aminoalcohols according to a very simple
method providing great yields in reaction products whereas
said reaction products are easily separated one from the
other.
Other characterizing features, advantages will
appear from the following description given by way of non-
limitative examples. In all examples, the percentages are
given by weight unless otherwise stated.

~52~
Example 1: Preparation of iminium chlorides
A number of methods for preparing iminium salts
is known from"Iminium &lts in Organic Chemistry', H. B~HME,
H.J. VIEHE Editions, Advances in Organic Chemistry, Volume
9, Part 1 and 2, (1976).
The simplest iminium salt of Formula CH2=N (CH3) 2
X is known as Eschenmoser salt and is commercially availa-
ble.
The inventors have prepared-the iminium salts by
treating at -80C the corresponding enamines as taught by
PETERSON in J. Am. Chem. Soc~ 79, 1 115 ~1957)by a hydrochloric
anhydrous solution within ether (approximately 3N). The
enamines were themselves prepared according to the method
of UMEN and HOUSE , organic synthesis, 53, 48 (1973), or
OPITZ et. al. Liebig Ann., 649, 36 and 47 (1961), or using
BEWZING Angew. Chem., 71, 521 (1959) or even according to
DULOV Bull. Soc. Chim. Fr., 967 (1960). The yield is prac-
tically quantitative in the iminium salts.
Example 2: Preparation of the a-amino alkyl tri-n-
butyltin compounds
.
According to the invention method, the -amino
alkyltributyltin compounds are obtained as above said through
simple chemical reaction for instance and preferably between
the tributylstannyl magnesium chloride and the corresponding
imm~nium halogen salt which is preferably a chloride salt.
~ ere-below is given a specific example of prepara-
tion ofa dimethylaminomethyltributyltin compound-which is the
simplest ~-aminoalkyltributyltin compound, the processing
conditions remaining identical for the preparation of any
other ~-aminoalkyltributyltin compound.
Within a trineck glass flask of 250 ml, previously
dried, are introduced 36.38 grams of tributyltin hydride
(o.125 mole ) to which is 510wly added dropwise one equiva-
lent of an etherified solution of isopropylmagnesium chlo-
ri~e (about 1N).

5Z~34
This reaction which is exothermic, produees a gas-
eous evolvement of propane. After complete addition, said
reaction medium which is milky white, is brought to reflux
with the aid of a lamp ( about 1~0 watts ) during about 2
hours.
Thereafter, are added at room ~erature, 9,35 grams
of iminium chloride (CH3 )2 N+ = CH2, Cl (0.1 mole) with the
aid of a "solid transfer 'container"; this salt addition is
performed by portions in view of minimizing the refluxes
caused by this exothermical reaction. This reaction is left
to be continued under stirring at room temperature during
2 hours, before hydrolyzing it through water addition at
O~C . ''
After extraction with ether, washing with water,
drying onto magnesium sulfate and evaporation of the solvent,
dimethylaminomethyltributyltin is isolated through distil-
lation under reduced pressure (Bpo 05 = 76C). 29,93 grams
are recovered corresponding to a yield of 86% by weight
with respect to the amount of the starting iminium chloride.
The dimethylaminomethyltributyltin compound is
identified through NMR of the proton and of tin 119 as well
as through dosage of the elements (C, H, N, Sn). The purity
thereof is higher or equal to 98~.
The data of the structural analysis are given here-
below:
.IH NMR (in CC14/TMS)
.......
Bu3SnCH2N(CH3) 2: butyl groups: ~.9 to 1.9 ppm
(27H);
(A) (B)
2.13 ppm (6H; singlet; B);
2.34 ppm (2 H; singlet with satellites,
JSnH = 22~7 Hz; A)
.~19sn NMR (in C6 D6/Me4Sn ex~nal standard)
.........

52~4
1 1
1 1 9
~ Sn = -33.6 ppm
Microanalyses
.............
C: (calc. = 51.76, obt. = 51.86/
H: (calc. = 10.16; obt. = 10.27/
N: (calc. = 3.99; obt. = 3.72/
Sn: (calc. = 34.08; obt. = 33.91.
Examples 3 to 7
In the following Table 1 are given the specific
-mono or disubstituted aminoalkyltributyltin compounds
prepared from the corres~onding iminium chloride salts
according to the procedure set forth in Example 2.
The boiling points and respective lHNMR datas of
the respective tin compounds of Examples 3 to 7 are the
following:
Example 3
Boiling point under 0.05 of reduced pressure:
103C. A B C D E
(CH3)2CH - CH - N(CH2-CH3)
SnBu 3
*lH NMR
0.9 to 1.9 ppm (40H, butyl groups +A+B+E) with
0.95 ppm (6HA, doublet J = 5.7 Hz)
2.29 ppm (4HD, quartet , 3J = 6.9 Hz)
2.49 ppm (1HC, doublet~ J = 8-9 Hz JsnH =
25.6 Hz).
Example 4
The boiling point under the same reduced pressure
was 131C and the NMR datas are as ~ollows:
A B C E
(CH3)2CH - CH - N
Sn~u3

:~2521~
*IH NMR
0.9 to 1.9 ppm (40H, butyl groups +A~B+E~ with
0.97 ppm (6HA, doublet, J = 6.~ Hz) and 1.46 ppm
t6HB, narrow absorbtion).
2.50 ppm (5H,broad absorbtion due to protons C
and D).
Example 5
The boiling point under the same reduced pressure
lO was of 147C and the NMR datas are as follows:
A B C D E F
(CH3 ) 2CH - CH - N (CH3 ` ~ CH2-~
SnBu 3
*lH NMR
0.9 to 1.9 ppm (34H, butyl groups +A+B) with
1.01 ppm (6HA, doublet, J = 5-3 Hz)
2.18 ppm (3HD, singlet , 2.61 ppm (1HC, doublet
9 7 Hz, JSnH 26 7 Hz)
3.37 ppm (1HE, doublet, .J = 13 3 Hz)
3.59 ppm (1HE, doublet, J = 13.3 Hz)
7.19 ppm (5HF, apparent singlet
Exam~le 6
The boiling point of the ti.n compound under the
same reduced pressure was 156-157~C and the NMR datas are
as follows:
A ~ < N ( CH 3 ) -CH -
SnBu 3
*lH N~
0.9 to 1.9 ppm (35H, butyl groups +A-~B)
2.21 ppm ( ~ , singlet)
3.43 ppm ( ~ , doublet, J = 11.6 Hz)
3.62 ppm ( ~ , doublet, J = 11.6 Hz)
7.16 ppm 15HE, apparent singlet)

~252~L~4
13
- EX~le ?
m is oo~pound wzs isoLated ~y means of liquid chromatography on
florisil (eluent: pentane)
The NMR datas were as follows:
~J
0.9 to 1.9 ppm (33H, butyl ~ s + 6 ~)
2.31 ppm (4Hc,multiplet)
3r32 ppm (1~ ,singlet, 2JsnH = 24,7 Hz)
7.02 ppm (5HA, apparent singlet)
Exan,ple 8: Influence of the Nature of the Halogen Within the
Iminium Halide
.
A prelimunary study performed onto the commercially available
im~nium salts so called EschenmDser salts has shown a oomparable reac-
tivity of said compounds as evidenced here belcw:
~ + Bu3SnMgCl
. Ether 3SnCH2NMe2 + MgXCl
X = Cl 86%
X = I 78%
,C=N ~ , Br 3 g ~ Ph-CH-N ~ Yield
H~C=N ~ ~ Br BU3SnM~Cl ~
~ H NMR data for Bu3Sn-CH N ~ :
0 g to 1.9 ppm (33 H, butyl group~6~ ) B ~
2.21 ppm (4 HD, multiplet) H A
3-29 ppm (1 Hc, singlet, .JsnH ~ 23.6 Hz) B
6.?6 ppm (2 HB, apparent singlet)
7.29 ppm (1 HA, apparent singlet)

~52~
14
From the above it can be concluded that the yield
is essentially the same irrespective of the nature of the
halogen. The chloride is preferred since it is the most
usual but in some cases bromine can be used when it is
easier to obtain the bromine salt.
Example 9: Influence of the Nature of the Metal
and of the Organic Radical Linked to Tin in the Stannyl
. . _
Anion
For studying this influence, the stannyl anion is
reacted with the commercially available Eschenmoser chloride
salt according to the following reaction:
~ R3Sn-M + CH2 = NMe2, Cl ~ R3SnCH2NMe2~ MCl
a. Influence of the metal (cation)
In the tributylstannyl series,tests have been
performed with Bu3SnLi within tetrahydrofurane , Bu3SnNa
within tetraglyme and Bu3SnK within dimethoxyethane with
each one is obtained Bu3SnCH2NMe2 with yields comparable or
lower than those obtainea with Bu3SnMgCl within ether.
In fact, tributylstannylmagnesium chloride is
preferred by the fact that it gives birth to very few amounts
of well-known side products (Bu6Sn2and some traces of Bu4Sn)
with respect to the tributylfitannylalkaline metals. Further,
ether (diethylether) used as solvent with the preferred
stannylmagnesium compound is the less costly and the easiest
to separate from the reaction medium.
b. Influence of the organic radicals linked to
tin in the stannylanion.
It has been observed that in the above chemi-
cal reaction the modification of the nature of the R substi-
tuent on tin does not modify the reaction. Through this
way it has been synthesized when R is respectively a methyl,
or a phenyl radical, the corresponding Me3SnCH2NMe~ and

~ ~25Z1~4
Ph3sncH2NMe 2 ~ with in both cases not optimized yields of
about 75% by weight.
Accordingly, there is no limitation as to the
nature of the organic radical linked to tin but from a prac~
tical viewpoint the trimethylstannyl compounds and the
triphenylstannyl compounds must be avoided due to the toxi-
city of the former and the problems of solubility of the
latter. Therefore, the tributylstannyl anions represent the
10 best compromise between toxicological and technical problems
for the time being.
The following three examples will illustrate the
application of the invention ~-aminated organotin or organo-
metallic compounds to the regiospecific preparation of ~-ami-
nated alcohols.
Example 10
Synthesis of the Macromerine (Halucinogen alkaloid)
The N,N dimethylaminomethyltributyltin of Example
1 is reacted with n-butyllithium in tetrahydrofnrane at
-78C thereby pxoviding the transme~allation and the forma-
tion of the corresponding N,N dimethylaminomethyl lithium
reagent.
This reagent is further reacted with the following
compound at room temperature:
_OMe
_OMe
f~
H O
To provide in 95% yield the following regiospecific ~-amino-
alcohol of formula: OH
Me~,~l --
Me NMe 2

~L2SZ~
Example 11: Synthesis of stovaine (local anaes~
thetic~
From the ~ame tin starting compound as in example
10 reacted with n-butyl lithium to obtain the corresponding
N,N dimethylaminomethyl lithium which is thereafter reacted
with methylethyl ketone and thereafter with benzoyl chloride
of formula PhCOCl to obtain stovaine of formula:
It
Ph - CO - C - CH NMe
O Me
The yield in stovaine is of 83% by weight calcu-
lated from the tin starting compound.
Exam~le 12
In this example, it is used as starting material
the organotin compound obtained in Example 7 which is at
first reacted with n-butyl lithium in tetrahydrofuran at -78C
to form the corresponding lithium compound of formula:
~ h
Li
N ~
Then, this lithium compound is further reacted
with 2-furylaldehyde at room temperature and then water is
added to the medium to hydrolyze the reaction product to
obtain the following ~-aminoalcohol of formula:
Ph ~ OH
0 ~ IQ
The yield in the final product is of 89 weight
percent with respect to the starting tin compound.
From the above illustrative examples 10 to 12, it
can be seen-that the yield in ~-aminoalcohol is very high
and has nothing to do with respect to the usual methods.

~XS~ 14
For instance, with respect to the synthesis of
macromerine of Example 10, the usual method described by
Braun & Hall in the Journal of Organic Chemistry, 37,(1972),
773 provides an overall yield of only 23 weight percent
with respect to the starting material.
Further, according to the present invention, all
the reactions are performed in the same reactor and can be
called as a one pot reaction.
Further, as shown by Example 10, it can be seen
that the aldehyde or ketone substrate reacted with the lithium
(metallic)c~x~nd can include reactive hydrogens for instance
from hydroxyl substituent. Indeed, the hydroxyl groups can
be protected or blocked easily through silylation according
to the method of Cooper in Chem. Ind; 794, (1978).
In view of the above, it can be seen that the
invention tin and metallic (preferably lithium) aminomethyl-
organic compounds can be used with any type of aldehyde or
ketone substrate to form the corresponding ~-aminoalcohols
with the best overall yields.
Further, the invention tin and metallic (prefer-
ably lithium) compounds are also useful as intermediates
for the synthesis of a great number of other compounds.

~ ;~5i2:~C314
18
~Aa~,
A I aYl-ld
~x N~ St~rtlng 101nlu0 Chlorldo o-smlnoslkyltrlbutyltln ~Z)
S~lt compound
l I __ B/A b r
c C N ~ R ?cS\Bu~ eolght
R R R NRIR~
Cl -
. ~ ,
Rl lo l~oproprl R~lo Ht
R~ ~ R` = othyl
_ _ __ . _
r CH~ ~nBu~
f H - C=N tCHI-CHl)~ ~CH - C~ F~
CHJ CHI NtcH~cHJ)2
_ _ _ Rl lo I-o ropyll R~lo H
R~ snd R~ together forn
ulth N s heterocyclic s~tur~ted rlng
_ - ~CH - C - N ~ l _ CN - C ~ ~ C7
Rl lo loopropyl~ R~ 18 Hl
R~ 1- nothyl snd R~ lu
bon2rl
_ _
CH~ H ~ CH~ CH ~ ~SnBu~
_ ~ ~1 ~ CH~
Rl nd R~ toqothAr or~
crclopentsne ring Rl is
0ethyl snd R` 18 ben~yl
6 _ 76
_ _ _ _.. _ _ _ ' - A -- . __
R~ 1~ Hl Rl lo ph~nyl
R snd R~ together ror0 8 hoterocycllc
H s~turetad rlng SnBu~
7 ~ C _ N~ ¦ ~ CH - N ~ 65
Cl