Solvent-Free Enantioselective Friedländer Condensation with Wet 1,1′-Binaphthalene-2,2′-diamine-Derived Prolinamides as Organocatalysts

Wet unsupported and supported 1,1′-binaphthalene-2,2′-diamine (BINAM) derived prolinamides are efficient organocatalysts under solvent-free conditions at room temperature to perform the synthesis of chiral tacrine analogues in good yields (up to 93%) and excellent enantioselectivies (up to 96%). The Friedländer reaction involved in this process takes place with several cyclohexanone derivatives and 2-aminoaromatic aldehydes, and it is compatible with the presence of either electron-withdrawing or electron-donating groups at the aromatic ring of the 2-aminoaryl aldehyde derivatives used as electrophiles. The reaction can be extended to cyclopentanone derivatives, affording a regioisomeric but separable mixture of products. The use of the wet silica gel supported organocatalyst, under solvent-free conditions, for this process led to the expected product (up to 87% enantiomeric excess), with its reuse being possible at least up to five times.

Andrewes, Will, autographed letter signed to John Winthrop; New Haven, 1 side (2 pages), 1652 January 24

Correspondence describing a distemper he was suffering from and requesting Winthrop send him medicine and instructions for taking it.

Bliss, Nathaniel, 1622-1654, autographed letter signed to John Winthrop; Springfield, Mass., 1 side (2 pages), 1652 December 21

Correspondence regarding an illness Bliss was suffering; he writes that the medicines Winthrop had given him were ineffective and he has been suffering fits. The letter, which was finished in an unknown hand, reports further symptoms had developed, including headache and blindness, and requests Winthrop again send instructions for taking the medicine he originally sent Bliss, and any other medicine he would recommend.

Clark, John, autographed letter signed to John Winthrop; Saybrooke [sic], Conn., 1 side (2 pages), undated

Correspondence regarding a vomit Winthrop prescribed to Clark's wife, and the lack of improvement of her symptoms, which she believed were possibly caused by chest worms.

Fitch, James, 1622-1702, autographed letter signed to John Winthrop; Saybrooke [sic], Conn., 1 side (2 pages), 1652 April

Correspondence requesting medicines from Winthrop for his stomach ailment, and for a neighbor who was suffering from edema.

Fuller, Robert, autographed letter signed to John Winthrop; Rehoboth, Mass., 1 side (2 pages), 1652 September 29

Correspondence seeking advice from Winthrop about an illness that afflicted his children's heads and caused hair loss, and his sister's case of worms.

Gerrard, Joseph, autographed letter signed to John Winthrope [sic]; Saybrooke [sic], Conn., 1 side (2 pages), undated

Correspondence requesting Winthrop send Gerrard a purge and other medicine to treat a urinary condition.

Hovey, Daniel, 1642-1695, autographed letter signed to John Winthrop; Ipswich, Mass., 1 side (2 pages), 1656 August 13

Correspondence relaying the progress of Hovey's stomach ailment after he took medicine prescribed by Winthrop, and further symptoms he was suffering, including chest pains. Hovey asks Winthrop for advice on additional action he should take to ease his symptoms.

Montague, Abigale, autographed letter signed to John Winthrop; Hadley, Mass., 1 side (2 pages), 1663 July 19

Correspondence about her seven-year-old daughter, who was suffering from inflammation and discharge from her eye, in which Montague requests Winthrop's advice on whether sarsaparilla root or English barley boiled with herbs would be an effective treatment. Montague adds a postscript about her own health, writing she has a "thick rotten fleame rising out of my stomach" but no cough.

Montague, Abigale, autographed letter signed to [ ] Barnerd, 1 side (2 pages), circa 1663 July

Correspondence entreating "Sister Barnerd" in Hartford, Connecticut, to speak to John Winthrop about an eye infection that afflicted Montague's daughter.

Pynchon, John, 1621-1703, autographed letter signed to John Winthrop; Springfield, Mass., 1 side (2 pages), 1663 July 24

Correspondence seeking Winthrop's advice regarding treatment of his daughter, who had been vomiting and suffering insomnia and dry mouth for several days

Rood, Sarah, autographed letter signed to John Winthrop, 1 side (2 pages), undated

Correspondence requesting Winthrop's advice for treating a condition Rood describes as a "falling out of [the] wome" (prolapsed uterus) that occurred after her first childbirth and has worsened with the birth of her second child.