I cannot provide a brief comment that would be sufficient for this exchange, so instead I am providing the synthetic methods reported in J. AM. CHEM. SOC. 2010, 132, 16677–16688, “Chemoselective Multicomponent One-Pot Assembly of Purine Precursors in Water”. The plausibility question arises when we try to imagine these conditions being met in an earth envisaged a few billion years ago – this should not be interpreted as criticism of the actual synthesis reported in this paper. It is grossly unfair to assume I am attacking such work, and anyone who reads this paper, or other ones, will note the authors a very circumspect in their discussion. Even beyond these methods, we are faced with even greater hurdles when we consider optical purity. I can post some of the reactions schemes in this paper if people are interested, but I think I have made my point.
General Synthetic Methods. Method A: A solution of aminoimidazole
2 or 3 (g1 equiv) and 2-aminooxazole 5 (1 equiv) in
D2O was adjusted to the desired pD. A solution of aldehyde (1
equiv) in D2O and, if required, DMSO-d6 was added. The pD was
adjusted as necessary by addition of DCl or NaOD, and the reaction
was volumetrically adjusted to the required concentration and then
incubated at the specified temperature. The progress of reactions
in deuterated solvents was directly monitored by NMR spectroscopy.
Method B: A solution of aminoimidazole 2 or 3 (g1 equiv) and
2-aminooxazole 5 (1 equiv) in H2O was adjusted to the desired
pH. A solution of aldehyde (1 equiv) in H2O was added. The pH
was adjusted as necessary by addition of HCl or NaOH, and the
reaction was volumetrically adjusted to the required concentration
and then incubated at the specified temperature. Reaction mixtures
were lyophilized and dissolved in deuterated solvents for NMR
spectroscopic studies. One or more diastereomeric products were
isolated from each reaction for charaterization.
Method C: An aqueous solution of cyanoacetylene (0.98 M, 3-5
equiv) was added to tetrahydroimidazo[1′,3′]-2′′-aminooxazolo[1′,2′]-
pyrimidines (20 mM), and the solution was then heated at 60 C
for 1-3 d with stirring. Analytical samples were removed and
lyophilized to assess reaction progress by 1H NMR spectroscopy.
rac-1′,2′,3′,N-Tetrahydroimidazo[1′,3′]-2′′-aminooxazolo[1′,2′]-
pyrimidine-4-carbonitrile (6). Method A: 5-Aminoimidazole-4-
carbonitrile 2 (24.8 mg, 0.23 mmol) and 2-aminooxazole 5 (20 mg,
0.23 mmol) were dissolved in D2O (1.0 mL) at pD 5.0, 6.0, or 7.0.
Formaldehyde (37%, 18.6 mg, 0.23 mmol) was added in D2O (0.5
mL), the pD was rechecked, and the reaction volume was adjusted
to 2 mL by the addition of D2O. The reactions were incubated at
room temperature, and the progress of the reaction was assessed
by 1H NMR spectroscopy (see Supporting Information, Figure S4,
for 1H NMR spectra at pD 5.0, 6.0, and 7.0). The formation of
rac-1′,2′,3′,N-tetrahydroimidazo[1′,3′]-2′′-aminooxazolo[1′,2′]-pyrimidine-
4-carbonitrile 6 was observed at all pD values. 6 was then
crystallized by cooling the reaction at pD 5.0 to 4 C for 2 d. 6
was isolated by filtration and washed with ice-cold water, and a
single crystal was removed for X-ray diffraction.
Method B: 5-Aminoimidazole-4-carbonitrile 2 (1.29 g, 11.9
mmol) and 2-aminooxazole 5 (1.00 g, 11.9 mmol) were dissolved
in H2O (10 mL) at pH 5.0. Formaldehyde (37%, 0.96 g, 11.9 mmol)
was added, the pH was rechecked, and the reaction volume was
adjusted to 20 mL with H2O. After 20 min a white precipitate had
formed in the reaction. The reaction was mechanically stirred for a
further 15 h. The solids present were isolated by filtration, and the
filtrate was lyophilized. The combined solids were redissolved in
aqueous methanol by heating and agitation. Slowly cooling to room
temperature gave 1.68 g (69%) of 6 as a white solid. Recrystallization
of the lyophilized filtrate afforded a further 0.5 g (20%) of 6.
.