Synthesis 2017; 49(03): 657-666
DOI: 10.1055/s-0036-1588075
paper
© Georg Thieme Verlag Stuttgart · New York

A Modular Synthesis of 2-Alkyl- and 2-Arylchromans via a Three-Step Sequence

Robert K. Orr*
a   Department of Process Chemistry, Merck Research Laboratories, 126 E Lincoln Ave, Rahway, NJ 07065, USA
,
Louis-Charles Campeau
a   Department of Process Chemistry, Merck Research Laboratories, 126 E Lincoln Ave, Rahway, NJ 07065, USA
,
Harry R. Chobanian
b   Department of Medicinal Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA
,
Jamie M. McCabe Dunn
a   Department of Process Chemistry, Merck Research Laboratories, 126 E Lincoln Ave, Rahway, NJ 07065, USA
,
Barbara Pio
b   Department of Medicinal Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA
,
Christopher W. Plummer
b   Department of Medicinal Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA
,
Andrew Nolting
c   Department of Process Chemistry, Merck Research Laboratories, 2000 Galloping Hill Rd, Kenilworth, NJ 07033, USA   Email: robert.orr@merck.com
,
Rebecca T. Ruck
a   Department of Process Chemistry, Merck Research Laboratories, 126 E Lincoln Ave, Rahway, NJ 07065, USA
› Author Affiliations
Further Information

Publication History

Received: 12 July 2016

Accepted after revision: 02 September 2016

Publication Date:
14 October 2016 (online)


Abstract

A convergent three-step method for the synthesis of 2-substituted chromans is described. These results have been accomplished via the Heck coupling of readily accessible allylic alcohols and 2-iodophenols, followed by reduction and Mitsunobu cyclization. The utility and generality of this method is demonstrated through the synthesis of a series of 2-aryl-, 2-heteroaryl- and 2-alkylchromans, as well as an azachroman derivative. The asymmetric version of this approach via a Noyori-catalyzed ketone reduction and subsequent cyclization is likewise highlighted.

Supporting Information

 
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