I have been building mobile line of business applications for a while now. Over the past few years, I have separated out the client and middle tier explicitly (using web-services). This has enabled me to rapidly build different front end applications for a range of different devices.
I have recently extended our timesheet application to run on iPhone/iPod Touches using a combination of .Net and the excellent IUI library built by Joe Hewitt.
One thing, I needed however was a calendar control mimicking Apples' own calendar application for use for timesheet entry. Its taken a while to build the control however its proven that you can go a long way down the web development path using Microsoft tools to develop something that arguably looks very similar to the iPhone’s user interface.
Using AJAX its possible to achieve the smooth user experience without having to reload pages. I’ve found the combination of IUI with a .Net middle tier a really work-able way of developing software.